Download Excited State Reactions of Carbonyl Compounds

Final 1.0, 4/13/2004
Excited State Reactions of Carbonyl Compounds
9. 1. Introduction
In this chapter we shall focus mainly on ketones and aldehydes.
In the ground state, the basic
chemistry of the carbonyl chromophore is to a large extent independent of the nature of the groups (aryl or
alkyl) attached to the carbonyl carbon. These groups by altering the electronic nature of the lowest excited state
can however have an enormous influence on the excited state chemical and physical behavior of the carbonyl
chromophore. In general, it is important to gain an understanding of the factors that control the nature of the
lowest excited state and also to obtain a model for the electronic configuration of the reactive state. In a
photochemical reaction a reactant is transformed into a product but between these two there are many events
that need to be understood. The primary questions (Figure 9.1) one should ask during analysis of a
photoreaction are (a) What are the products of the photoreaction? (b) What are the electronic characters of the
reactive state? (c) What are the spin characters of the reactive state? (d) What intermediates are involved in the
reaction? (e) What orbitals are involved and how do they interact during the chemical transformation? (f)
What are the various chemical and physical processes and what are their rates with which a reaction of interest
competes?
hn
R
P
hn
*R
R
hn
R
1*R
ISC
P
I
3*R
3I
ISC
1I
P
Figure 9.1
1
Final 1.0, 4/13/2004
9. 2. Reactive State
The electrons that are of importance in deciding the reactivity of the carbonyl chromophore are the two
lone pairs on the oxygen and the two electrons in the p-bond connecting the carbon and oxygen. Excitation of
a lone pair electron to the p* level results in an np* excited state. Similar excitation of a p-electron to the p*
level results in a pp* excited state. Each of these singlet excited states (np* and pp*) has a corresponding
triplet state. For example, acetone’s lowest singlet excited state is np* in nature and the second excited state in
the singlet manifold is of pp* character. In the triplet manifold there will be the corresponding np* and pp*
states. Since, in the case of dialkyl ketones, the energy difference between np* and pp* singlets is large, the
ordering of the nature of the states is preserved in the triplet manifold as well. Thus, the reactive states, namely
the lowest excited singlet and lowest excited triplet states, of dialkyl ketones are of np* character. This
ordering is rarely altered by either the medium or by alkyl group substitution.
The energy diagrams for acetone and biacetyl are shown in Figure 9.2. It is important to note that the
rates of photophysical processes from S1 (intersystem crossing from S1 to T1 as well as radiative transition to
S0 ) are not very high suggesting that dialkyl ketones (for which we have taken acetone as an examplar) can
react, under favorable conditions, from both S1 and T1. The state energy diagram for benzophenone is shown
in Figure 5.16. An important point to note is that the gap between the 1 np* and 1 pp* states for benzophenone
is smaller than for acetone. The expected splitting between 1 pp* and the corresponding 3 pp* being much
larger than that between the np* states, a closer 1 pp* and 1 np* states result in 3 pp* being lower than 1 np*.
Under such conditions, as discussed in Chapter 5 the intersystem crossing rate from S1(np*) to T1(pp*) is
much larger (El Sayed’s rule). Hence we would predict that diaryl ketones (aryl alkyl ketones as well) would
react only from T1 but not from S1. If a reaction is to take place from S1 it should be able to compete with the
very fast intersystem crossing process (>101 0 sec-1). Such could be expected for intramolecular but not for
intermolecular reactions.
2
Final 1.0, 4/13/2004
O
Figure 9. 2
Figure 5.15 and 5.10 (reproduced)
3
Final 1.0, 4/13/2004
The magnitude of the gap between 1 np* and 1 pp* states can also have an impact on the ordering of the
states in the triplet manifold. As seen in Figure 5.10 a decrease in the 1 np* and 1 pp* gap results in 3 pp*
being lower than 3 np* state. Thus depending on the nature of the aryl group (e.g., phenyl, naphthyl, or anthryl
group), the electronic configuration of the lowest excited singlet as well as triplet states can change and this will
influence the rate of intersystem crossing. For example, while for acetophenone and benzophenone the lowest
triplet has np* character that for pyrenealdehyde, 2-acetonaphthone and fluorenone the lowest triplet is pp* in
character.
The subtle dependence on the nature of the lowest excited state for a number of acetophenones,
benzophenones and valerophenones on the substituent is listed in Table 9. 1. From the table it is clear that the
triplet lifetime is very much dependent on the substituent on the aryl ring. For example, the triplet lifetime of
valerophenone (VP) in 2-methylpentane at 77°K is 0.0064 sec while that for 4-methoxy VP is 0.45 sec. This
large difference is due to the difference in nature of the emitting state in these two cases. While in VP it is np*
that in 4-methoxy VP it is pp*. A point to note is that in all cases the emitting states may not be such ‘pure’
states. For example, 4-methyl VP and 4-fluoro VP have lifetimes of 0.13 and 0.039 sec, in between that of VP
and 4-methoxy VP. Such intermediate values indicate that the emitting states are not ‘pure’ np* and pp*
states but a mixture of the two (for a discussion on state mixing see sections 5.8-5.10). Another point to note
from Table 9. 1 is that the ketones may show two emissions with different lifetimes. These come from two
close lying T1 and T2 states having different extents of np* and pp* character. In general, electron-donating
substituents such as CH3 and OCH3 stabilize the pp* state, and electron withdrawing groups such as CF3 and
CN stabilize the np* state.
State configuration mixing is a common phenomenon with most chromophores (Chapter 5). The
extent of mixing depends on the energy gap between the two states and availability of a vibration that would
mix the two electronic configurations. Therefore, it is important to recognize that no excited state can be
represented by a single configuration, especially so when there is another excited state within 5 kcal/mole.
9.3.
Electronic Configuration of Reactive States
4
Final 1.0, 4/13/2004
In the ground electronic configuration, the electrons present in the p-orbital of a carbonyl chromophore
are polarized in such a way that the carbonyl carbon is positively polarized. Most reactions of the carbonyl
chromophore in the ground state can be understood on the basis of this simple model. The non-bonding lone
pair present on the oxygen is nucleophilic, and many electrophilic reactions with the carbonyl chromophore
evolve from this face (n-face).
Just like the ground state, the carbonyl chromophore possessing an np* electronic configuration is also
a bipolar species, but the dipole is reduced relative to that of the ground state. For example, the dipole moment
of benzophenone in the ground state is 2.9 D while that in the np* triplet state is 2.1 D. The double bond
character of the carbonyl chromophore is reduced in the np* state compared to that in the ground state. This is
also indicated by the C=O stretching frequency in the case of 4-trifluoromethylacetophenone and
benzophenone both of which have np* as the lowest triplets. For 4-trifluoromethylacetophenone the C=O
stretching in the ground state is 1696 cm-1 while that in the np* state is 1326 cm-1. For benzophenone the C=O
stretching frequency in the S0 and T1 states are 1665 and 1222 cm-1.
In the np* excited state a chemical reaction can occur either along the n-or p-plane. The characteristics
of the orbital involved being different, different reactivities are expected on these two planes. The np* state is
both electrophilic and radical-like in the plane containing the n-orbital (Figure 6.13; Chapter 6). The p-plane,
which contains 3 electrons, is electron rich and nucleophilic. Although the overall dipole moment is still
towards oxygen, in the p* orbital the carbonyl carbon is electron rich compared to oxygen. (Remember that a
nonbonding electron from oxygen has been removed and placed between the two atoms to be shared). This
simple picture of the np* state holds true for both dialkyl, aryl alkyl and diaryl carbonyl compounds. In the
latter two systems the p* orbital is delocalized into the aryl ring while in the dialkyl ketones this is localized on
the C=O chromophore. This difference in the character of the p* orbital does not alter the general reactivity of
the carbonyl chromophore along the n-orbital.
The frontier orbital diagram for the np* state along with the orbital levels of a few generic molecules is
is shown in Figure 9.3. Based on this picture, the singly occupied n-orbital which may be considered to be in
need of an electron is expected to interact with a filled C–C s bond, a C–H s bond, a C=C p-bond, or a pair of
5
Final 1.0, 4/13/2004
non-bonded electrons. Since the second p-orbital which is required to complete product formation is in a plane
perpendicular to the n-orbital, the interaction between n-orbital and filled s, p or n-orbital alone is not sufficient
to form a stable product. Therefore the interactions shown in Figure 9.3 are expected to result in an
intermediate such as diradical or radical ion pair. Figure 9.3 lists also n-orbital initiated reactions of carbonyl
compounds.
(Electron poor olefin)
Oxetane p*C=C
(Electron rich olefin)
Oxetane pC=C
p*
s*CC
b-Cleavage
nN (lone pair) Electron Transfer
n
sCH
a-Cleavage sCC
Hydrogen abstraction
p
Figure 9. 3
The singly occupied p* orbital is higher in energy and is more willing to donate or share its electron
with a center carrying a lower lying empty orbital (LUMO) (Figure 9.3). For example, the p* orbital of the
carbonyl would be expected to interact with the p* orbital of electron poor alkenes and s* orbital of a weak
C—C bond. Since in the p* orbital the carbon center is more electron rich than the oxygen end of the
carbonyl chromophore, a nucleophilic attack will be initiated by the carbon center. Expected reactions from this
type of interaction are listed in Figure 9.3.
6
Final 1.0, 4/13/2004
In the pp* state the lone pair (n-orbital) on the oxygen remains intact, and there are electronic changes
only on the p-face. Although on the basis of first principles one might expect the pp* excited carbonyl to
behave similar to an alkene, the fact that the electron distribution in p and p* orbitals is unequal between
carbon and oxygen of the C=O bond would make it behave slightly differently. Since neither 1 pp* nor 3 pp*
are the lowest excited states in alkyl ketones and aldehydes we will not consider these further. On the other
hand, depending on the nature of the aryl group and the substituent on the aryl ring, the pp* triplet could
become the lowest state in aryl and diaryl ketones. In these systems both p and p* orbitals are delocalized into
the aryl ring. Because of this, the pp* state of aryl and diaryl ketones are likely to be less reactive than the np*
triplet. The frontier orbital interaction diagram for pp* excited state is shown in Figure 9.4. Based on the
interactions shown electron transfer, hydrogen abstraction, [2+2] addition, and b-cleavge are expected.
The dipole moment of pp* triplets of several aryl ketones have been estimated to be higher than that in
the ground state. For example, the dipole moment of 2,5-dimethoxybenzaldehyde is 3.0 and 4.5 in S0 and T1
(pp*) states. This suggests that in the pp* state the electron density is shifted from the aryl ring to the
carbonyl chromophore. Although the electron density is shifted from the ring to the chromophore, in the p*
state still the carbon (of C=O) is more electron rich than the oxygen. As indicated by the IR frequency of the
C=O stretching, the double bond character in the T1 (pp*) state is reduced but not to the same degree as in T1
(np*) state. The C=O stretching frequencies for 4-methoxy acetophenone in S0 and T1 (pp*) states are 1676
and 1462 cm-1 respectively.
9.4. A Close Analogue of the Reactive np* Carbonyl Chromophore
The closest chemical analogue of an np* excited carbonyl chromophore is an alkoxy radical. The two
are compared in Figure 9.5. Like the oxygen atom of an np* excited carbonyl compound, oxygen of the
alkoxy radical contains a reactive half filled n-orbital. If one ignores the p-face of the np* excited carbonyl
group, the close similarity between alkoxy radicals and np* excited carbonyl compounds is obvious.
Assuming for a moment that this is true, we can predict the reactivity of np* excited carbonyl compounds on
the basis of the behavior of alkoxy radicals. Alkoxy radicals (a) abstract hydrogen from hydrocarbons, and (b)
7
Final 1.0, 4/13/2004
undergo cleavage of the s-bond connected to the alkoxy carbon (b-cleavage) and (c) react with alkenes. The
np* excited carbonyl chromophore also undergoes all these reactions.
Hydrogen abstraction
Addition to C=C bond
a-Cleavage
Figure 9.5
9. 5. Photoreduction: Addition to a C—H bond
Reduction in the ground state is one of the most useful reactions of carbonyl chromophore. A number
of reagents have been developed to selectively reduce carbonyl chromophores present as a part of various
functional groups (ester vs. ketone etc.). However, one can‘t selectively reduce in the ground state, for
example, acetophenone in presence of 4-methoxy acetophenone or acetone in presence of acetophenone. But
these processes can be carried out photochemically. Photochemical reduction of carbonyl compounds is a
useful complimentary method to the numerous thermal methods. In addition to its synthetic utility, since this is
one of the ubiquitous reactions excited ketones and aldehydes undergo in almost any organic solvent, one
needs to understand the mechanisms of photochemical hydrogen abstraction by carbonyl compounds.
The irradiation of ketones and aldehydes in the presence of hydrogen-atom-donating substrates
(alcohols, hydrocarbons, amines etc.) commonly results in the photochemical process of hydrogen abstraction,
followed by product formation via secondary thermal reactions (Scheme 9.1). The primary bond-forming
step in this transformation is the addition of a hydrogen atom to the C=O chromophore to form a new O—H
bond. Formation of a new O—H bond can occur by way of two mechanisms: (a) direct abstraction of a
hydrogen atom (Scheme 9.1), or (b) an electron transfer followed by a proton transfer (Scheme 9.2). The
reduction occurs from both np* and pp* states. The characteristics of these two processes are slightly
different, and will also be discussed in this section.
8
Final 1.0, 4/13/2004
OH
Ph
hn
O
+
2
Ph2CHOH
Ph
Ph
Ph
Ph
C
Ph
HO
OH
Ph
Ph
OH
Ph
CH3
+
C
hn
+
O
Ph
PhCH2
Ph
Ph
Ph
OH
Ph
Ph
Ph
OH
Ph
OH
+
PhCH2CH2Ph
+
Ph
H
OH
Ph2C = O
+
hn
CH3OH
+
HOH2C
Ph
C
CH2OH
Ph
OH
H
O
+
C
Ph
Ph
Ph
OH
Ph
OH
C
O
OH
Ph
+
H
Ph
Ph
hn
CH3
Ph
C
PhC
H
OH
OH
OH
Ph + CH3
Ph
CH2OH
OH
Ph + CH3
C
CH3
H
O
Ph
Ph
C
Ph
OH
OH
O
Ph
Ph
Ph
Ph
C
Ph
+ CH3
C
CH3
OH
Scheme 9.1
9
Final 1.0, 4/13/2004
*3
O
Ph
C
Ph
Ph
+
(CH3)2NPh
C
Ph
O
N
Ph
Ph
proton transfer
Ph
C
CH3
OH + CH2
N
CH3
Ph
CH3
OH
OH
Ph
CH
Ph
C
Ph
Ph
Scheme 9.2
9. 6. Photoreduction of carbonyl in the np* state via hydrogen abstraction
Benzophenone is photoreduced by a number of hydrogen atom donors such as isopropanol,
benzhydrol, ethers and toluene (Scheme 9.1). Both chemical and physical evidence support the fact that the
reactive state is the triplet np* state (see Chapter 8). The key primary intermediate in all these reactions is a
benzophenone ketyl radical. Direct spectroscopic evidence for the benzophenone ketyl radical is available
from time resolved ESR, transient absorption, and transient emission studies.
OH OH
coupling
O
OH
OH
hn
2
OH
OH
+
disproportionation
H
O
hydrogen transfer
OH
+
H
Scheme 9.3
10
Final 1.0, 4/13/2004
In principle, when two radicals meet, three processes can occur: a reverse hydrogen transfer to yield the
starting reactants, a radical coupling reaction to yield a coupling product, and a disproportionation reaction to
yield oxidation-reduction products (Scheme 9.3). Which pathway is preferred depends on the radical pair. For
example, during the photoreduction of benzophenone inspite of the np* triplet being the reactive state and the
benzophenone ketyl radical the primary intermediate, the ultimate product isolated varies depending on the
nature of the hydrogen donor and the conditions used for irradiation. When benzophenone is irradiated in
toluene, one isolates three products, benzpinacol, 1,2-diphenylethane and diphenyl benzyl carbinol (Scheme
9.1). Formation of these three products is easily understood on the basis of the intermediacy of benzophenone
ketyl radical and benzyl radical. For example, when methanol is used as the hydrogen source, benzpinacol,
mixed pinacol and a product dervied from a para coupling reaction are obtained (Scheme 9.1).
Based on what we know about the photophysics of dialkyl, aryl alkyl and diaryl ketones/aldehydes (see
Section 9.2), we can predict that aryl-alkyl and diaryl ketones and aryl aldehydes will react only from their
triplet states, whereas hydrogen abstraction from the S1 and T1 states of dialkyl ketones is likely. This is what
has been found experimentally. For example, in the case of acetone the S1 and T1 states are both reduced by
iso-propanol and tributyl tin hydride. The rate of hydrogen abstraction in the S1 state is slightly higher than in
T1 . In spite of the higher rate of hydrogen abstraction in the S1 state the quantum yield of reduction product
formation is lower in S1 state than in T1 state. The rates of hydrogen abstraction by acetone in S1 and T1 states
from iso-propanol are 9.1x106 and 1x106 M-1s-1 and from tributyl tin hydride are 1x109 M-1s-1 and 5.4x108 M1 -1
s respectively. The lower efficiency (<25%) of product formation from S1 in spite of higher rate of hydrogen
abstraction could be due to fast back hydrogen transfer between the singlet geminate radical pair (Scheme 9.3).
The photoreduction of acetone by iso-propanol results in products from both coupling and
disproportionation. The occurrence of disproportionation is not apparent in the analysis of the products of
photoreduction, since the enol is unstable under the reaction conditions (Scheme 9.3). The formation of enols
in intermolecular hydrogen abstraction reactions was first discovered by the observation of 1 H-NMR signals
ascribable to enols in CIDNP experiments. Confirmation that disproportionation of the radical pair can occur
11
Final 1.0, 4/13/2004
via abstraction of a hydrogen atom from the carbon rather than the oxygen of the acetone ketyl radical
intermediate has been obtained by product analyses in which d6 -acetone was irradiated in isopropanol to give
deuterated isopropanol. The CIDNP experiments established that the enol products are stable for seconds at
room temperature. In fact, irradiation at -70° C yields a stable acetone enol that has been characterzied by
NMR. This technique of generating enols has been used to determine the equilibrium constants for keto-enol
tautomerism for a number of ketones and aldehydes.
From the above presentation it is clear that ketones abstract hydrogens from hydrogen donors to yield
radical intermediates. Hydrogen abstraction is also one of the primary reactions of the alkoxy radical. Note
that the relative rates of hydrogen atom abstraction by triplet benzophenone and t-butoxy radical are in the
similar range (Scheme 9.4).
Ph
OH
hn
O
Ph2CHOH
Ph
Ph
C
Ph
HO
Ph
Ph
Ph
OH
Ph
Rate of hydrogen abstraction by triplet benzophenone: 5x106 M-1s-1
Solvent
Reaction
Rate constant
(M-1 s-1)
ButO• + PhCH3
ButOH + PhCH 2•
Benzene/ t-
2.3 x 105
butyl peroxide
ButO• + PhCH2 CH3
ButOH + PhCH(•)CH3
Benzene/ t-
1.05 x 106
butyl peroxide
ButO• + CH 3CHOHCH3
ButOH + CH3 C(•)OHCH3
Benzene/ t-
1.8 x 106
butyl peroxide
t
Bu O• +
Benzene/ t-
t
Bu OH +
5.4 x 107
butyl peroxide
Scheme 9.4
12
Final 1.0, 4/13/2004
Table 9.2 summarizes some experimental data for the quenching (kq ) of np* triplets of three ketones
with varying triplet energies by hydrogen atom donors of different bond strengths. The range of values spans
several orders of magnitude. For substrates possessing strong C—H bonds (e.g., acetone, acetonitrile),
hydrogen abstraction is extremely inefficient (kq <103 ). For a given donor, the ketone with the higher triplet
energy has a higher kq . This is evident when one compares the kq values for the quenching of acetone and
biacetyl triplets by iso-propanol. The difference in triplet energy of ~30 kcal/mole reduces the kq values by two
orders of magnitude. Thus np* hydrogen abstraction is subject to the simple rules of thermodynamics, i.e. (a)
more stable the intermediate radical pairs faster the reaction and (b) more energetic the reactants faster the
hydrogen abstraction. A qualitative diagram shown in Figure 9.6 aptly describes the situation. When the
energies of the radical pair are higher than the triplet energy of the ketone the hydrogen abstraction would be
endothermic and less likely to occur. When the energies of the radical pair is lower than the triplet energy of
the ketone the hydrogen abstraction would be exothermic and the reduction is likley to occur. The rate of
hydrogen abstraction is related to the exothermicity of the reaction.
Figure 9.6
13
Final 1.0, 4/13/2004
Table 9.1 (From MMP, p. 374)
14
Final 1.0, 4/13/2004
9. 7. Photoreduction of the carbonyl pp* state via hydrogen abstraction
Reluctant photoreduction of aryl alkyl and diaryl ketones/aldehydes having lowest pp* triplet states is
known. A comparsion of the rates of hydrogen abstraction by several substituted acetophenones with varying
np* and pp* character is provided in Scheme 9.5.
Systems that have low-lying np* triplets certainly react
faster (by three orders of magnitude) than the ones with pp* character. When the pp* and np* states are
farther apart (>10 kcal/mole) and the lowest excited state is pp*, the reduction is presumed to occur from the
‘pure’ pp* state. Under such conditions, the rate of reduction is lower than that from np* state. Two relevant
examples in Scheme 9.5 are benzophenone and para-phenyl benzophenone. Systems with pp* triplet that
react slowly are the polynuclear aromatic ketones such as naphthyl phenyl ketones. The observed rate
represents the inherent hydrogen abstraction ability of a carbonyl in the ‘pure’ pp* state (~103 M-1s-1).
kr M-1s-1
O
*3
OH
2x106
OH
O *3
OH
1x103
OH
O
*3
OH
1.6x106
OH
O
*3
OH
1.6x105
OH
H3C
O
H3C
*3
OH
3.2x104
OH H3C
H3C
CH3
CH3
Scheme 9.5
15
Final 1.0, 4/13/2004
Low hydrogen abstraction rate constants do not necessarily mean low quantum yield of photoreduction.
Benzophenone and 4-phenyl benzophenone abstract hydrogen from iso-propanol at a rate of 106 and 103 M-1S1
respectively. This is consistent with the lowest excited state being np* in the former and pp* in the latter. In
spite of the low rate of hydrogen abstraction a fairly high quantum yield (0.3) of reduction is obtained for 4phenyl benzophenone (p,p* )3 in iso-propanol as the solvent. The high quantum yield arises because, at very
high concentrations of hydrogen donor (as the solvent), all the triplets react via hydrogen abstraction: i.e.
kr[RH] >> Skd.
One can also improve the efficiency of the photoreduction of ketones with low-lying 3 pp* states by
using powerful hydrogen donors. For example, naphthyl ketones are photoreduced efficiently by tin hydrides.
The Sn—H bond is quite weak, and therefore tin hydrides serve as substrates for photoreduction of even pp*
triplets. In the case of 2-acetonaphthone, kr is ~106 M-1 sec-1, i.e., of the order for benzophenone triplets with
iso-propanol as a substrate.
Why does a pp* excited carbonyl compound have a lower reactivity, and how does a carbonyl group
with a low-lying pp* state abstract hydrogen? To answer these questions we need to take a closer look at the
nature of the two states (see also Section 9.3 in this chapter). The pp* state is not intrinsically unreactive
towards hydrogen donors. It should be noted that a pure pp* states of C=C as well as C=S are capable of
abstracting a hydrogen atom from a hydrogen donor (see Section 9.x). In simple terms, hydrogen abstraction
may be viewed as a reaction that is initiated by the interaction of a singly occupied orbital of the carbonyl and
the C—H s orbital (Figures 9.7 and 9.8). Better interaction leads to a faster rate. The preferred interactions
for np* and pp* states are shown Figures 9.7 and 9.8. The np* state being a localized state, the orbital
coefficent on the ‘n’ orbital is 1. Therefore, a good overlap between the ‘n’ orbital of C=O and the C—H s
orbital is expected. The pp* state certainly cannot beat this situation as the electrons in the p and p* orbitals
are delocalized over the carbonyl and the aromatic rings. In other words, since the single electron in the p*
orbital is diffused, a rapid attack by C=O on the C—H is unlikely. Of the two centers in C=O, oxygen
abstracts the hydrogen as it yields a more stable product (R2 C°–OH) than the one (R2 CH–O°) obtained
(R2 CH–O°) via carbon abstracting the hydrogen. This conclusion could also be drawn by analyzing the orbital
16
Final 1.0, 4/13/2004
interaction between p, p* and sC—H orbitals (Figure 9.8). The main interaction that leads to hydrogen
abstraction is the one between the partially occupied p of C=O and sC—H orbitals. In the p orbital of the
carbonyl, the orbital co-efficient being much larger on oxygen the interaction is expected to occur at this center
which would lead to R2 C°–OH.
In-plane approach
Perpendicular approach
X
H
H
s* LUMO
X
s* LUMO
No Bonding
p*
Large energy gap
n
E1
E1
p
s HOMO
H
s HOMO
C
O
H
C
First Excited State (np*)
Figure 9.7
17
Final 1.0, 4/13/2004
In-plane approach
X
X
H
H
O
O
O
H
H
X
X
s* LUMO
E2
C
C
O
O
p*
n
p
C
E1
O
s HOMO
H
O
C
First Excited State (pp*)
Figure 9.8
9. 8. Consequences of close-lying np* and pp* triplets
When the pp* and np* states are closer (<5 kcal/mole) and the lowest excited state is pp*, the rate of
hydrogen abstraction will be higher than that expected for a pp* state but is likely to be lower than that for a
pure np* state. This can be understood on the basis of two models: (a) state mixing and (b) state equilibrium
(Scheme 9.6; see also sections 4.23). The ‘state mixing’ model assumes that when two states are close-by the
two states cannot be ‘pure’ states and each is contaminated by the other. Thus the reactivity of the pp* is
18
Final 1.0, 4/13/2004
borrowed from that of np* character. In the ‘state equilibrium’ model, the pp* reactivity comes from low
concentrations of the np* triplet in equilibrium with the lower pp* state (Scheme 9.6). Equations in Scheme
9.6 describes the rate constants for hydrogen abstraction, with the np* state providing most or all of the
reactivity when DE between the np* and pp* states is less than 5 kcal/mole. The rate of hydrogen abstraction
from isopropanol by 4-trifluoromethylacetophenone (np* triplet) is 8.8x106 M-1sec-1 while that for 4methylacetophenone (pp* triplet) is 6.7x104 M-1sec-1. The reactivity of the two ketones differ by two orders of
magnitude clearly illustrating that the pp* (4-methylacetopheone) is less reactive than np* triplet (ptrifluoromethylacetophenone). The fact that acetophenone is in between these two values (2.1x106 M-1sec-1)
suggests that the reactive triplet in this case is mixed with pp* character. A point to note is that in spite of
having nearly same triplet energy all acetophenones may not abstract hydrogen from the same donor with the
same rate. The observed rate is a reflection of the contributions of np* and pp* characters to the reactive state.
np *3 + pp *3
Products
n p* 3
pp *3 + np *3
p p* 3
Reaction from np* state
Activated reaction
Rate depends on the gap
H
Products
The two states are not pure
Reactivity depends on extent of mixing
and np* character
n,p
k obs = cn,p k H
+ cp,p k
p, p
H
cn,p = (1 - cp,p) = e-DE/RT 1 + e-DE/RT
Scheme 9.6
9. 9. Photoreduction of carbonyl (np* state) via electron and charge transfer
Irradiation of benzophenone in tert-butanol leads to no product. On the other hand, irradiation of
benzophenone in tert-butyl amine leads to benzpinacol. Benzophenone triplet is not quenched by tert-butanol
19
Final 1.0, 4/13/2004
but it is quenched by tert-butyl amine at ~108 M-1s-1 (benzene solvent).
Benzophenone is reduced to
benzpinacol by isopropanol with a limiting quantum yield of 2. On the other hand, it is reduced by sec-butyl
amine with a limiting quantum yield of 1.2. This reduction in quantum yield occurs in spite of the higher rate
of quenching of benzophenone triplet by sec-butyl amine (~108 M-1s-1); compared with ~106 M-1s-1 by
isopropanol). The rates of quenching of the excited carbonyls by amines are listed in Table 9.2. Clearly the
rates are much higher than by alcohols and the rates show a relationship with the ionization potential than with
C–H bond energies.
In spite of differences, certain features of the reduction by amines and alcohols are the same. The spin
configuration of the reactive state of the carbonyl compound is the same, triplet. The intermediate that has been
characterized during reduction by amines is benzophenone ketyl radical, the same one that was identified
during the reduction by alcohols. Let us focus on the first step, the interaction between the benzophenone
triplet and the reducing agents, amine and alcohol. The first step during the reduction by isopropanol has been
identified as the hydrogen atom abstraction. If this is the mechanism by which reduction by amine occurs, one
would expect the rate of quenching by amine to be not more than 106 M-1s-1. In fact the rate is higher by two
orders of magnitude. The rate of hydrogen abstraction surprisingly is independent of the bond energy of the
C—H bond being abstracted. On the other hand, there is a linear correlation between the ionization potential
of the amine and the rate of quenching. Such a relationship , suggests that the primary interaction between a
carbonyl triplet and an amine has charge transfer character (exciplex) (Scheme 9.7).
kE
Ar2CO* + R2NCH3
d
d
[Ar 2CO R 2NCH3]*
kr
d
d
[Ar 2CO R 2NCH3]*
Ar2COH + R2NCH2
Scheme 9.7
Quantum yields of ketyl radical formation from ketone triplets in which amines are hydrogen donors
have been estimated to be near unity. Benzophenone ketyl radical is formed from both tert-butyl amine and
20
Final 1.0, 4/13/2004
triethylamine, indicating that the NH as well as the a CH hydrogens are abstracted readily within the CT
complex. In spite of the high quantum yield of benzophenone ketyl radical formation, the overall quantum
yield of reduction is low. This is believed to be due to a disproportionation reaction (Scheme 9.8), which is
absent when isopropanol is used as the hydrogen source.
Ar2C=O*(T 1) + RCH2NR'2
k ir
[Ar 2C-O-
RCH 2NR'2 ]
kh
Back electron transfer
Ar2C=O + RCH2NR'2
Ar2COH
+
Proton transfer
RCHNR' 2
Disproportionation/
back hydrogen transfer
OH
Ar
C
CHNR2
Ar
R
+
Ph
HO
Ph
Ph
OH
Ph
Scheme 9.8
21
Final 1.0, 4/13/2004
The reduction by amines can be visualized as taking place by orbital interaction between the half filled
n-orbital of the carbonyl oxygen and the doubly occupied n-orbital of the amine nitrogen (Scheme 9.9). Such
an interaction is expected to lead to a flow of an electron from the amine to the carbonyl oxygen. By this
process the oxygen gains partial negative charge and becomes the active site for the next step, namely proton
transfer. When there is a full electron transfer radical ions are formed and if they escape the cage could be
detected by spectroscopic methods such as ESR. The main difference between reduction by an alcohol and an
amine is that, in the former process, both an electron and a proton (i.e., hydrogen atom) move simultaneously
towards the carbonyl oxygen, whereas in the latter, the proton follows the electron.
C
O
p*
p*
n
n
C
n
p
p
O
NH2
O
O
H
np*
pp*
O
NH2
H
Scheme 9.9
9. 10. Photoreduction of carbonyl (pp* state) via electron and charge transfer
22
Final 1.0, 4/13/2004
Fluorenone, para-phenylbenzophenone, 2-acetonaphthone and 4-aminobenzophenone systems with
pp* as lowest triplets, which are not reduced efficiently by isopropanol are reduced by sec-butyl amine to the
corresponding pinacols. A linear dependence of the quenching rate on the ionization potential of the amine
indicates that the quenching mechanism involves an electron flow from the amine to the excited
ketone/aldehyde. The quenching may be visualized as occurring through the interaction of the singly occupied
p-orbital of the carbonyl group and the lone pair n-orbital of the amine nitrogen (Scheme 9.9). Such an
overlap is expected to result in electron transfer from amine to carbonyl to yield R2 C°–O- . Thus independent
of the nature of the reactive state (np* or pp*) the resulting intermediate as well as the final products are the
same.
9. 11. Competition between hydrogen abstraction and charge transfer
Any quenchers that have low oxidation potentials can interact with the excited carbonyl by a charge
transfer process. Such a process in principle can lead to photoreduction of the carbonyl chromophore.
Example of this type would be the photoreduction of xanthone (np*3 ) and azaxanthone (pp* 3 ) by electron
rich alkylbenzenes (Scheme 9.10). The triplets of these two ketones might be quenched by alkylbenzenes
such as toluene or para-xylene by either hydrogen or a charge transfer quenching process. The occurrence of
photoreduction by charge transfer rather than hydrogen atom abstraction is evidenced by the following
observations:
•
The rate constants for photoreduction by charge-transfer are higher than those expected for radicallike hydrogen atom abstraction, based on an alkoxy radical model (Scheme 9.10).
•
The quantum yields are solvent-polarity dependent.
•
pp* states are more efficiently photoreduced by a hydrogen donor capable of reactivity via a
charge-transfer mechanism than by hydrogen donors capable only of hydrogen atom transfer.
•
In favorable cases, direct spectroscopic evidence for radical cations produced by complete electron
transfer, can be obtained.
23
Final 1.0, 4/13/2004
xanthone
quencher
Get (eV) kq (M-1 s-1)
1-axaxanthone
ketyl radical
Get (eV) kq (M-1 s-1)
ketyl radical
TOL
1.00
5.8 x 106
0.53
0.66
1.6 x 108
0.38
m-XYL
0.74
4.6 x 107
0.49
0.40
1.1 x 109
0.36
MES
0.71
2.2 x 108
0.45
0.37
3.1x 109
0.46
DUR
0. 44
1.1 x 109
1.0
0.10
1.1 x 1010
0.70
Scheme 9.10
Let us suppose that photoreduction occurs and we wish to determine whether a hydrogen atom
abstraction or an electron transfer mechanism is operating. An example of such a case occurs in the
photoreduction of acetophenones by alkyl substituted arenes (Scheme 9.11). The products evidently arise
from radical coupling, and an electron transfer or a hydrogen abstraction mechanism may be written to
rationalize product formation. Of these possibilities, only the hydrogen abstraction process should display a
kinetic deuterium isotope effect. Thus, if the reaction rate constant is not sensitive to replacement of C-H by CD, the rate-determining step probably involves electron transfer rather than hydrogen abstraction. Furthermore,
we expect that if an electron transfer mechanism operates, the sensitivity of the rate constants to ionization
potential will be much greater than expected for a hydrogen abstraction process.
24
Final 1.0, 4/13/2004
O
C
Ph
CH3
T1 (n, p*)
Charge transfer
+
O
+
CH
C
Ph
CH
CH3
OH
Hydrogen abstraction
Ph
C
CH3
+
C
Scheme 9.11
Table 9.3 presents some data on the photoreduction of acetophenone and trifluoromethyl phenyl
ketone by toluene and p-xylene. The data is interpreted as follows: Hydrogen abstraction occurs when
acetophenone is the reactive species and electron transfer occurs when trifluoromethyl phenyl ketone is the
reactive species. This conclusion is consistent with (a) the presence of a large deuterium isotope effect observed
in the photoreduction of acetophenone by toluene and the absence of an isotope effect in the photoreduction of
trifluoromethyl ketone, and (b) the much greater rate enhancement for the trifluoro ketone as one changes from
toluene to p-xylene. The greater inefficiency of photoreduction in the case of the trifluoromethyl phenyl ketone
(compare the F of reduction of acetophenone (0.13) and trifluoromethylacetophenone (0.053) by toluene) is
interpreted to result from a rapid back electron transfer (to generate ground states) in competition with proton
transfer (to generate a radical pair). In general, reduction by hydrogen abstraction occurs when the electron
transfer process is endothermic (Rehm-Weller equation) and proceeds via an electron transfer (or charge
transfer) pathway when it is exothermic (Scheme 9.12). Whether the reduction will occur at all will depend
upon the energetics of the radical products with respect to the triplet energy of the carbonyl system (Figure
9.6)
25
Final 1.0, 4/13/2004
Table 9.3 (from MMP p. 385)
26
Final 1.0, 4/13/2004
O
+
RH
O *3 + RH
O *3 + RNH2
OH + R
O
+ RNH2
OH + R
O + RNH2
O + RH
Scheme 9.12
Charge transfer interaction between excited ketones and even benzene solvent is likely. For example,
benzophenone and xanthone triplets are quenched by benzene with rate constants of 1.3x104 M-1s-1 and 5x105
M-1s-1. These quenchings are believed to involve either an interaction between the electrophilic n-orbital and porbitals of benzene or nucleophilic p face of carbonyl and p* orbitals of benzene (Scheme 9.13).
O*
Scheme 9.13
27
Final 1.0, 4/13/2004
9.12. Intramolecular Photoreduction
Intramolecular hydrogen abstraction is no different from the intermolecular process discussed above.
Of the various known intramolecular hydrogen abstraction process g- hydrogen (1,5) abstraction is by far the
most common process and this is discussed in the next section. When appropriate geometry can be attained
during the excited state lifetime abstraction from positions other than g- is also known. Examples of 1,6; 1,7;
1,8; and 1,9 hydrogen abstractions are provided in Scheme 9.14. When there are both g as well as other
(b, d, e, etc.) hydrogens available, in general g-hydrogen abstraction is preferred. This is attributed to the ease
of formation of a six membered chair-like transition state compared to any other cyclic transition state.
All variations of the intermolecular hydrogen abstraction mechanisms are known also in the case of
intramolecular hydrogen abstraction: (a) A ketone with pp* excited triplet reacts slower than the one with np*
state (Scheme 9.15, eq. 1). (b) The presence of an electron donor on the chain favors charge transfer initiated
hydrogen abstraction process (Scheme 9.15, eqs. 2 and 3)).
28
Final 1.0, 4/13/2004
RCH2
O
R
O
O
OH
hn
Ph
Ph
RO
RO
HO
CH 3
Ph
O
CH 2
CH
C
Ph
hn
Ph
hn
O
OH
Ph
O
Me
O
O
Ph
Me
O
hn
O
CH 3
Ph
HO
Ph
O
O
H
Ph
hn
Ph
H
Ph
OH
Ph
OH
Ph
+
O
O
Scheme 9.14
29
Final 1.0, 4/13/2004
hn
(1)
pp*
Ph
CHPh
CHPh
Ph
O
Ph
OH
Ph
OH
H
O
HO
hu
Ph
NMe 2
Od
-
NMe 2
H
Ph
d+
NMe 2
HO
H
Ph
OH
NMe 2
NMe 2
Ph
Ph
CO2Me
O
CO2Me
CO2Me
N
hn
HO
Z
N
Ph
(2)
+
+
N
Ph
Z
(3)
HO
Ph
Z
Ph
Ph
Ph
Z = tosyl or benzoyl
Scheme 9.15
9.13. g-Hydrogen abstraction: Norrish Type II reaction and Yang Cyclization
Irradiation of 2-pentanone possessing g-hydrogen atoms yields acetone and ethylene (R = CH3 in
Scheme 9.16). Products have been rationalized to have risen via a cleavage of the b C—C bond. Since this
reaction was originally discovered by Norrish and there was already a Norrish type I reaction (a-cleavge), the
new reaction was called the Norrish type II reaction. Yang first isolated cyclobutanols by irradiation of
30
Final 1.0, 4/13/2004
dialkylketones possessing g- hydrogen atoms (Scheme 9.16). Cyclobutanol formation prompted by ghydrogen abstraction is generally called the Yang cyclization. Yang was also the first to work out the
correlation between g-hydrogen abstraction, b-cleavage and cyclization. The connection was made through a
1,4-diradical intermediate (Scheme 15). In this section we discuss the mechanism of g-hydrogen abstraction,
the reactive state(s) involved, and the identification, characterization and behavior of the 1,4-diradical
intermediate.
HO
OH
R
hn
C
R
OH
R
OH
O
+
R
R
Scheme 9.16
O H
O
hn
OH
II
HO
OH
HO
+
A
B
Scheme 9.17
Evidence in favor of a diradical intermediate came from irradiation of 6-heptene-2-one. In addition to
the expected cyclobutanol photoproduct A, a cyclohexenol derivative B was also isolated (Scheme 9.17).
31
Final 1.0, 4/13/2004
Should the reaction proceed via a concerted process, only cyclobutanol should be formed. The fact that a
cyclohexenol accompanies cyclobutanol formation indicates that a 1,4-diradical may be involved (Scheme
9.17).
S1(n, p*)
T1 (n, p*)
H
C
C
CH2
Ph
H
CH2CH3
O
CH3
CH2
CH3
O
C
C
CH2
Ph
CH2CH3
CH2
CH3
O
C
CH2CH3
C
Ph
CH3
H
CH2
CH2
optically pure
O
hn
H
C
Ph
CH2
C
PhCOCH 3
CH3
CH2CH3
CH2
+
racemic
CH2
C
CH2CH3
OH CH3
Ph
CH2CH3
Scheme 9.18
Another aspect of this reaction became evident when optically pure (+)-4-methyl-1-phenylhexanone
was irradiated (Scheme 9.18). The recovered starting ketone following brief irradiation showed loss of optical
activity. This can happen only if g-hydrogen abstraction occurs reversibly. Thus, the three common reactions
of the 1,4-diradical intermediate are cyclization, cleavage and hydrogen reversal.
32
Final 1.0, 4/13/2004
The 1,4-diradical has been chemically interrogated by several means. The earliest observation involves
the solvent dependent behavior of aryl alkyl ketones. For example, the quantum yield of product formation
from valerophenone in benzene is 0.4, while in tert-butanol it is 1.0. Further, when an optically active ketone is
irradiated in tert-butanol, racemization of the starting material via back hydrogen transfer could be completely
suppressed. These two effects have been rationalized on the basis of hydrogen bonding of the tert-butanol to
the intermediate 1,4-diradical (Scheme 9.19). The hydrogen bonding is believed to alter the preferred
conformation of the 1,4-diradical intermediate and influence the decay process of the 1,4-diradical.
Of the
three modes of decay, cyclization, cleavage and hydrogen reversal, only reverse hydrogen transfer results in the
breakage of the hydrogen bond. Thus the enhanced quantum yield and reduced racemization in hydrogen
bonding solvents are the direct result of interception of the 1,4-diradical intermediate by the solvent.
Ph
O
R
Ph
Solvent
H
Ph
O
Solvent
R1
R
H
R1
Racemization
O
R
O
H
R1
R
PhCCH 3 + CH2=C
R1
Scheme 9.19
As discussed in Chapter 8, the 1,4-diradical intermediate from aryl alkyl ketones has also been
intercepted by reagents such as thiols, methyl methacrylate, di-tert-butyl seleneketone, and HBr (Scheme 8.x).
In these cases, the more reactive alkyl radical terminus forms a covalent bond with the trapping agent. Direct
spectroscopic detection of the 1,4-diradical has been possible, and the lifetimes of a number of systems have
been measured to be in the range of 10–200 ns (Chapter 8).
33
Final 1.0, 4/13/2004
Based on our understanding of the spectroscopy of carbonyl systems (see section 9. 2), we anticipate
that dialkyl ketones will undergo g-hydrogen abstraction from both their excited singlet and triplet states, and
that aryl alkyl ketones should react through their excited triplets only. This has been found to be true. For
example, the g-hydrogen abstraction reaction of 2-hexanone (a dialkyl ketone) cannot be completely quenched
by the triplet quencher 1,3-pentadiene. On the other hand, the g-hydrogen abstraction reaction of valeropheone
(an aryl alkyl ketone) can be completely quenched.
Lack of complete quenching suggests that a part of the
reaction come from the excited singlet state.
On the basis of the kinetics and thermodynamics of the intermolecular hydrogen abstraction process
(section 9.6) the rate of g-hydrogen abstraction would be expected to depend on the bond strength of the
C—H bond.
The kr values for several ketones shown in Table 9.4 are consistent with this expectation.
Perusal of Table 9.4 also indicates that systems with low-lying pp* triplets abstract g-hydrogen at a slower
rate than those with lowest np* triplets. This is consistent with what we have learned earlier for intermolecular
hydrogen abstraction. An elegant illustration of this can be found in the photochemistry of 1-benzoyl-4anisylbutane (Scheme 9.20). Although potentially both ends can react, the major products (>90%) come from
the more reactive benzoyl end of the molecule.
OMe
O*
O
2 x 10
OMe
7
+
O
O
107
108
OMe
O
O
1 x 10
OMe
5
+
O
O*
Scheme 9.20
34
Final 1.0, 4/13/2004
Table 9.4 (from MMP p. 388)
35
Final 1.0, 4/13/2004
A linear relationship with a slope (r value) of –1.85 observed between the s-values of the d-substituents in
valerophenones and kr suggests that intramolecular hydrogen abstraction is initiated by an electrophilic attack
of the half vacant n-orbital on oxygen. This requires that the C—H bond be aligned with the oxygen n-orbital,
a coplanar approach. It is important to note that the structure of the excited ketone is tetrahedral and not planar
as in the ground state. Therefore the co-planarity postulate should be considered only as an approximate
guide.
An important difference between inter- and intramolecular hydrogen abstraction concerns the relative
geometry between the carbonyl group and the C—H bond. While an unconstrained hydrogen atom donor can
explore many geometries of approach within the lifetime of the excited state species before it finds an ideal one,
the hydrogen donor that is constrained by a methylene chain will not be able to do so.
C—H bond is situated favorably, the g-hydrogen abstraction process may fail.
Therefore, unless the
For example, irradiation of
trans-4-tert-butyl-2,6-di-n-propyl cyclohexanone, yields the axial isomer A, which is relatively stable to further
irradiation (Scheme 9.21). This result requires that the equatorial n-propyl side chain be more readily involved
in a g-hydrogen abstraction reaction than the axial side chain. Indeed, the equatorial, but not the axial side
chain, is capable of achieving the required geometry for hydrogen abstraction without producing severe
molecular distortion. Another elegant example of this phenomenon is provided by ketones shown in Scheme
9.22. The only product observed upon irradiation of ketone A is the bicyclic alcohol formed via the Yang
cyclization. In contrast, irradiation of the isomeric ketone B gave only benzaldehyde and ketone C, products of
a Norrish type I reaction as the primary photoproducts. Only in the former ketone can the carbonyl n-orbital
reach a g-hydrogen.
O
O
(equatorial)
hn
(axial)
(axial)
Scheme 9.21
A
36
Final 1.0, 4/13/2004
O
Ph
Ph
hn
OH
A
B
Ph
hn
O
Ph
PhCHO +
O
C
D
Scheme 9.22
Restriction of conformational freedom in the starting ketone is also a source of rate enhancement. The
mobility of the participating molecules (carbonyl compound and hydrogen donor) is severely restricted at the
transition state during the intermolecular hydrogen abstraction process. This restriction will cost in terms of
entropy of activation. When the carbonyl group and the hydrogen donor are linked, DS‡ is less than when
they are not linked. This is reflected in the different values of kr for intermolecular abstraction of hydrogen by
acetophenone from cyclohexane and intramolecular g-hydrogen abstraction by valerophenone. The difference
in kr is more than two orders of magnitude! According to this model, the more one freezes the bond rotations
in the starting ketone, the higher the rate of hydrogen abstraction. This is illustrated with examples in Scheme
9.23 (the abstracted hydrogen in all three examples are secondary and the variations in DH# are likely to be
small). Remember that it is not enough to freeze the positions of the hydrogens but they should be properly
aligned.
O
O
O
Ph
kH
1.3 x 108
6 x 10 8
Ph
7 x 10 9
Scheme 9.23
37
Final 1.0, 4/13/2004
9.14. 1,4 Diradicals as intermediates in g-hydrogen abstraction
When initially formed, the 1,4-diradical generated via g-hydrogen abstraction, would (ideally) have its
two p-orbitals perpendicular to each other and would be present in a folded conformation (Scheme 9.24). The
only reaction the diradical generated in folded conformation can undergo is the reverse hydrogen transfer. By
rotating about its terminal or central C—C bonds the 1,4-diradical can adopt cisoid or transoid conformations,
(Scheme 9.24). The 1,4-diradical that exists in the conformations shown in Scheme 9.24, can in principle
undergo three reactions: cyclization, fragmentation and reverse hydrogen transfer. The geometric requirements
for each of these reactions are slightly different. The fragmentation process can only occur when the two porbitals of the 1,4-diradical are parallel to the central C—C s-bond that is being broken Thus fragmentation
can occur from both cisoid and transoid conformations. Both cyclization and reverse hydrogen transfer
require that the two ends of the diradical be close to each other, i.e., it requires a cisoid conformation.
However, for cyclization to occur, the two p-orbitals should face each other, whereas for reverse hydrogen
transfer, the p-orbital at the alkyl end should face the O—H s-bond (i.e., the two p orbitals should be
perpendicular to each other.
R
O
R
HO
HO
R
OH
H
R
OH
R
HO
R
HO
+
R
Scheme 9.24
38
Final 1.0, 4/13/2004
Depending on the nature of the reactive state the generated 1,4-diradical can be either in the singlet
(1 DR) or triplet state (3 DR). Since the lifetime of 1 DR is much shorter than 3 DR the final products obtained
from these two diradicals are expected to be different. The 1 DR generally does not live long enough to
undergo bond rotations. The photobehavior of optically pure 5-methyl-2-heptanone illustrates this point.
Quantum yields of racemization (of the reactant ketone) upon excitation of (S)-(+)-5-methyl-2-heptanone in
presence and absence of the triplet quencher 1,3-pentadiene (2.5 M) are provided in Scheme 9.25.
The
quantum yields in presence of 1,3-pentadiene correspond to the reaction of 1 DR from the excited singlet state
of (S)-(+)-5-methyl-2-heptanone. Under this condition, the F of racemization is low (0.002). In the absence
of the triplet quencher 1,3-pentadiene, the reaction from both S1 and T1 takes place. As seen in Scheme 9.25
under such conditions the F of racemization of the starting ketone is higher (0.08). The photobehavior of (S)(+)-5-methyl-2-heptanone indicates that the 1 DR is too short lived to yield racemized starting ketone.
OH
OH
hu
O
CH3
H
C
CH2
C
O
CH2CH3
CH3
C
CH2CH3
H
CH3
OH
CH2
OH
+
CH3
C
+
CH2
CH2
Solvent
f racemization
Hexane
0.08 + 0.02
t-Butyl alcohol
0.04 + 0.02
Hexane + 2.5M
cis-1,3-pentadiene
0.002 + 0.019a
Scheme 9.25
The 1,4-diradical that is formed from the triplet excited states of dialkyl and aryl alkyl ketones is a
triplet species (3 DR). Since the final isolated products have all electron spins paired (closed shell products)
39
Final 1.0, 4/13/2004
intersystem crossing (ISC) from 3 DR to 1 DR must precede product formation. In the absence of any external
perturbation the lifetimes of triplet diradicals (3 DR) are in the range of 10 to 200 ns and this assures that triplet
diradicals attain conformational equilibrium (Scheme 9.26) before they intersystem cross to the singlet state
(1 DR). If the ISC rates are the same for all conformers, then the product distribution will be a direct reflection
of the equilibrium distribution of the conformers. In some cases, it is likely that each conformer may have
different intrinsic rates of ISC, and if this is the case, the product distribution is not a reflection of the
conformer distribution and it would represent the rate of ISC.
3
HO
R
HO
R
OH
R
kisc
kisc
R
kisc
HO
R
HO
R
OH
HO
R
kisc
HO
R
Slow
1
Fast
O
R
H
OH
R
HO
+
R
Scheme 9.26
The ISC rate from 3 DR to 1 DR can be enhanced by paramagnetic quenchers such as oxygen, di-tertbutyl nitroxide and Cu (II) derivatives. Such physical quenchers will shorten the lifetime of a 3 DR and thereby
prevent it from establishing an equilibrium between various conformers. The product distribution obtained
under such conditions will be different from the one obtained under conditions under which 3 DR establishes an
equilibrium with various conformers. For example, in the case of g-methylvalerophenone, the presence of ditert-butyl nitroxide enhances fragmentation yields by >200%. Recall that the product distribution is a reflection
40
Final 1.0, 4/13/2004
of the conformer that crossed from the triplet to singlet spin configuration. Since the product distributions are
different in the presence and absence of the paramagnetic quencher, the conformer that intersystem crosses
more effectively in its presence and in its absence must be different.
Two factors determine the product distribution from the triplet diradical: (a) the rate of ISC from 3 DR
to 1 DR and (b) the specific conformer population of 3 DR at the equilibrium. In the absence of a complete
understanding of the factors that control ISC rates in 1,4-diradicals, our ability to control the product
distribution seems limited. In spite of this handicap, certain trends emerge. Of the conformers shown in
Scheme 9.25 the transoid is most likely the lowest energy one. This conformation is ideally suited for the
cleavage process; the transition state for the cleavage process will be lowered when there is an overlap between
the terminal p-orbitals and the central s-bond undergoing cleavage. This geometry allows the maximum
development of the double bond character of both the enol and the alkene as the central bond breaks. Thus with
most systems that react from triplet state we would expect higher percentage of cleavage compared to
cyclization. Further, thermodynamics favors clevage over cyclization. These conclusions are generally true.
Normally with most systems less than 25% of the product corresponds to cyclization. Under special
circumstances when the alignment required for elimination is not possible fragmentation will have higher
activation energy, and by default cyclization and reverse hydrogen transfer become preferred; much higher
yield of cyclization product is obatined. Several examples of this type are known (Scheme 9.27) in cyclic
ketones.
Ph
HO
O
Ph
hn
OH
HO
Ph
Ph
H
H
+
hn
O
Ph
HO
Ph
HO
Ph
No transoid diradical and the two p-orbitals can't become parallel
to the central s-bond. No fragmentation, only cyclization.
Scheme 9.27
41
Final 1.0, 4/13/2004
9.15. Conformational effects in Norrish Type II reaction and Yang Cyclization
1-Methylcyclohexylphenyl ketone (Scheme 9.28) can exist in two conformations. In one the reactive
benzoyl group is axial and in the other equatorial. The geometry of the molecule is such that only when the
benzoyl group is axial can it undergoes the g-hydrogen abstraction. The conformer that has the benzoyl group
in the equatorial position can undergo only a-cleavage. Thus upon excitation the two interconverting
conformers are expected to undergo different reactions- the g-hydrogen abstraction and a-cleavage. Which
products are formed depends on two factors: (a) the rate of interconversion between the two conformers in the
excited state and (b) the rates of the two reactions (g-hydrogen abstraction and a-cleavage). The rate of
interconversion between the two conformers and the rates of the two reactions are provided in Scheme 9.28.
Since the conformers in their excited states react faster than they interconvert, it follows that the product
quantum yields should depend upon the conformer populations (in the ground state as well as excited state)
and the efficiency of product formation from each conformer, but not on the relative rate constants of the ghydrogen abstraction and a-cleavage reactions.
Product yields obtained are consistent with this analysis.
This analysis predicts that 1-methylcyclohexylphenyl ketone should have two triplets with distinct lifetimes,
one due to the axial and the other to the equatorial conformer. In fact quenching of product formation with the
triplet quencher naphthalene reveals this nicely (Figure 9.9).
Figure 9.9
42
Final 1.0, 4/13/2004
Ph
C=O (axial)
5
-1
10 s
(equatorial)
O
H3 C
C
Ph
hn
hn
Ph
Ph
C
H3 C
C=O*
OH
k H = 1.7 x 108 s-1
H
H3 C
H
H
CH3
O*
105 s-1
H
H
C
Ph
k a cleavage = 2.5 x 107 s-1
CH3
PhCO +
CH3
H3 C
Ph
PhCHO
OH
+
H3 C
Scheme 9.28
9. 16. Intramolecular Hydrogen Transfer by a Tunneling Mechanism
An important difference between inter- and inramolecular hydrogen abstraction is that the
intramolecular hydrogen abstraction in special cases may proceed by a hydrogen tunneling mechanism that is
unlikely during intermolecular hydrogen abstraction process. Surprisingly, anthrone and tetralone systems
undergo intramolecular hydrogen abstraction even at temperatures as low as 20 K. The energy of activation for
hydrogen abstraction both during inter- and intramolecular process has been determined to be in the range of
2-3 kcal/mole. Such a barrier would be insurmountable at 20 K. In spite of this, intramolecular hydrogen
abstraction of 1,4-dimethyl anthrone (Scheme 9.29) occurs and no phosphorescence from this ketone is
detectable at this temperature. The primary mechanism of hydrogen abstraction at very low temperatures (<30
K) has been identified to be a tunneling process.
43
Final 1.0, 4/13/2004
1
O
H
C
H
H
3
O
H
C
H
H
H
H
S
CH3
T
CH3
O
C
hn
O
1,4-MAT
CH3
CH3
OH
Photoenol
CH2
CH3
CH3
Scheme 9.29
The name tunneling implies that the reactants may ‘tunnel’ through the classical potential to reach the
products without possessing the thermal energy necessary to go over the barrier (Figure 9.10). Quantum
mechanical tunneling originates from the fact that the location of the tunneling particle cannot be accurately
represented by a classical potential. The wave function describing the location of the tunneling particle does
not vanish at the turning points but it permeates through the barrier with a probability that is inversely
proportional to its mass and to the height and width of the barrier (Figure 9.11). Tunneling is possible for
lighter nuclei in lower vibrational states if there is a finite portion of the vibrational wave function beyond the
classical limit which overlaps with a vibrational wave function in the product well (Figure 9.11). Since the
permeability of the wave function decreases with increasing particle size, tunneling is most common in
reactions where a proton, hydride, or hydrogen atom transfer is part of the mechanism. It should be kept in
mind that even with light atoms the probability of tunneling is very small. Although tunneling may occur at all
temperatures, at high temperatures the activated reaction dominates the total rate. As the temperature decreases,
reaction over the barrier is slowed down enough for tunneling to contribute significantly to the total rate.
Tunneling rates of the lighter isotope (e.g., H) are greater than those of the heavier isotope (e.g., D) and the
44
Final 1.0, 4/13/2004
corresponding tunneling correction is larger. At the lowest temperatures, the thermally activated process may be
completely arrested such that only tunneling contributes to the total rate.
Figure 9.10
Figure 9.11
Since the tunneling will become dominant only at very low temperatures, and unless the hydrogen to be
abstracted is properly oriented, diffusional and conformational restrictions will prevent the hydrogen transfer
from taking place both by conventional and tunneling mechanisms. At 20K the hydrogen transfer by a
tunneling mechanism will occur only if there is a strong structural similarity between the reactant and the
product.
A remarkable influence of tunneling is obvious when phosphorescence yields and lifetimes of 2,3dimethylanthrone, 1,4-dimethylanthrone-d8 , and 1,4-dimethylanthrone are compared. In non-polar glasses at
77K, 2,3-dimethylanthrone decays with a lifetime of 3 msec and a quantum yield of emission near unity
(Figure 9.12). In the isomer 1,4-dimethylanthrone the ortho methyl group is ideally positioned for reaction
and it reacts so fast that it dominates the triplet decay. No phosphorescence is seen from this system at 77K
and therefore no lifetime could be measured. When the hydrogens in the ortho-methyl group are substituted
with deuterium, an expected isotope effect slows down the reaction enough for emission to compete. The yield
of emission is much lower than that of the model compound, 2,3-dimethylanthrone. The fact that reaction can
45
Final 1.0, 4/13/2004
be observed at temperatures as low as 15-20K suggests that reaction occurs by quantum mechanical tunneling.
This has been confirmed by Arrhenius analysis of reaction rate data obtained from the triplet decay rates.
Figure 9.12
The observed products due to intramolecular hydrogen abstraction, short triplet lifetimes and low
phosphorescence intensities of the reactant ketone, as well as the large isotope effects are more likley to be due
to tunneling below 30K than due to a conventional hydrogen abstraction mechanism. Thus one should keep in
mind that at very low temperatures, especially in rigid systems hydrogen abstraction by tunneling is a
possibility.
46
Final 1.0, 4/13/2004
9. 17. The Norrish Type I Reaction (a-cleavage process)
A number of carbonyl compounds (cyclic and acyclic ketones and arylalkyl ketones) upon excitation
give products resulting from an a-cleavge process. This reaction, originally reported by Ciamician and Silber
and developed by Norrish, is called the Norrish Type I reaction, and has become a useful synthetic tool in
making strained compounds, novel reactive intermediates and natural products.
The fact that np* excited carbonyl compounds undergo a-cleavage is expected on the basis of their
similarity to alkoxy radicals (Scheme 9.30).
Many features of the a-cleavage process occurring from an
excited np* state can be predicted on the basis of the known behavior of alkoxy radicals. In the b-cleavage
reaction of alkoxy radicals (note b-cleavage of an alkoxy radical corresponds to a-cleavage of a carbonyl;
b with respect to oxygen and a with respect to carbonyl carbon) it has been established that the substituent that
fragments is the one corresponding to the generation of the more stable radical. This in turn corresponds to
cleavage of the weakest bond b to the radical center. On this basis, we can postulate that, for an np* state of a
given multiplicity, the a-cleavage that produces the more stable radical pair will occur faster. For example, in
the case of phenyl tert-butyl ketone, the tert-butyl radical being more stable than phenyl radical a-cleavage
would occur to produce the former (Scheme 9.31). Acetone is not expected to undergo NorrishType I
reaction.
k ~ 102 sec-1
O
CH3
CH3
R2
C
CH3
O
R1
R1
O
C
O +
R3
O
CH3
CH3
CH3
O
hn
No Cleavage
CH3
CH3
CH3
CH3
R2
R3
R1
R1
C
R3
O
k ~ 109 sec-1
O
C
O +
R3
CH3
C(CH3)3
O
CH3
CH3
CH2
C(CH3)3
np*
O
Scheme 9.30
CH3
k ~ 109 sec-1
C(CH3)3
O
C(CH3)3
CH3
47
Final 1.0, 4/13/2004
O
O
hn
PhCC(CH3)3
PhC
O
+ C(CH3)3
PhCH
HC(CH3)3 + H2C
+
C(CH3)2
Scheme 9.31
ka (np*3)
3.3 x 107sec-1
4.7 x 108sec-1
Ph
H
1.8 x 109sec-1
O
O
Ph
O
O
O
H
1.6 x 106 sec-1
O
Ph
Ph
H3C
H
2.1 x 107 sec-1
Ph
Ph
H3C
CH3
1.2 x 108 sec-1
Scheme 9.32
We may use the alkoxy radical model as a rough guide for reactivity relationships. For molecules of
similar structure, the more stable the radical pair produced by a-cleavage, the faster will be the absolute rate
constant for reaction. An elegant illustration of the dependence of the rate of cleavage on radical stability is
provided by substituted cyclopentanones and cyclohexanones (Scheme 9.32 and Table 9.5). In cyclic
systems, the reactivity pattern of ring opening of alkoxy radicals follows that expected for the relief of ring
strain (Scheme 9.33). Similar results are found photochemically.
For example, the rate of a-cleavage of
cyclobutanone in Sl (np*) is at least 10 times faster than the rate of a-cleavage of cyclopentanone in Sl (np*)
(Table 9.5).
48
Final 1.0, 4/13/2004
R
O
O
R
O
R
<
<
Alkoxy radicals
Rate of a-cleavage
Increasing ring strain
O*
O*
<
O*
<
n, p* states
Rate of a-cleavage
Increasing ring strain
Scheme 9.33
If the radical stability matters, one would expect the excitation energy of the ketone that is undergoing
the cleavage would also have an influence on the rate of cleavage. In fact this is the case. For the same
electronic configuration and spin multiplicity, dialkyl ketones (RCOR), which have higher excitation energies,
undergo a-cleavage to R°CO and °R radicals faster than the analogous aryl alkyl ketones (ArCOR) (Scheme
9.34).
O
O
hn
k ~ 107sec-1
Ph
O
H3C
hn
O
H3C
C(CH3)3
k < 109 sec-1
ET = 73 kcal/mol
ET = 80 kcal/mol
Scheme 9.34
The dependence of the rate of cleavage on radical stability, on relief of ring strain and the excited state
energy suggests that there is a barrier for cleavage in the excited state. Consistent with the above expectation the
activation energies (~2-7 kcal/mole) have been measured for the a-cleavage of ketones in the excited state.
49
Final 1.0, 4/13/2004
Although there is no doubt (see below) that the final product of an a-cleavage reaction in most systems is a
diradical, the nature of the transition state during the cleavage is not fully resolved. Indications that the
transition state has some ionic character are available in the literature (see discussion on deoxybenzoins,
benzoin ethers and dibenzylketones).
9. 18. Diradical Intermediate
Thus far we have assumed that a-cleavage yields a radical pair or a diradical. The experimental
evidence for homolytic a-cleavage of ketones is substantial. In addition to the consistency of product structures
and structure-reactivity relationships with homolytic cleavage, direct spectroscopic identification has been
reported for both the acyl and the alkyl radical. For example, irradiation of methyl tert-butyl ketone in the
cavity of an ESR spectrometer results in direct observation of the ESR signal of the CH3 °CO and (CH3 )3 C°
radicals. In addition, CIDNP studies provide further support that acyl and alkyl radicals are produced.
Acylalkyl diradicals have been intercepted by n-butylmercaptan, nitric oxide and butadiene (Scheme 9.35).
Direct detection of the acylalkyl diradicals from numerous cyclic systems has also been possible, and the
lifetimes have been estimated to be in the range 10-100 ns.
O
O
O
+ NO
NO
hn
O
O
hn
O
O
-78o C
Scheme 9.35
9. 19. Nature of the Reactive State
In general, the a-cleavage reaction occurs from the lowest np* excited state. Ketones/aldehydes with
lowest pp* excited states either do not undergo a-cleavage or do so with low rate constants.
For example,
50
Final 1.0, 4/13/2004
phenyl tert-butyl ketone (Tl = np *; ET~73 kcal/mole) undergoes relatively rapid and efficient a-cleavage
(ka~107 sec-1; Fa~0.16 in benzene), but 4-methoxy-phenyl tert-butyl ketone (T1 = pp*; ET= 71 kcal/mole) is
stable toward cleavage (rate estimated to be less than 7x105 sec-1; Fa~0.0 in benzene) (Scheme 9.36).
O
O
hn
k ~ 107sec-1
Ph
O
hn
Ph
O
C
C(CH3)3
k < 105 sec-1
H3CO
Scheme 9.36
A non-intuitive aspect of a-cleavage is the fact that Tl (np*) reacts much faster than the corresponding
singlet (S1 ). For example, the rate constant for a-cleavage of Sl (np*) of tetramethylcyclopentanone is at least
102 times slower than the rate constant for a-cleavage of the same compound from T1 (n, p*) (Table 9.5). In
the case of di-tert-butyl ketone the rates of a-cleavage from S1 and T1 have been estimated to be ~ 6x107 and
8x109 sec-1 respectively. This is surprising considering the fact that S1 (np*) is more energetic than Tl (np*).
The explanation could lie in differences in the activation energies or the Arhenius A factors or both. The A
factor for both Sl (np*) and Tl (np*) have been measured, and it is smaller for the Sl (108 sec-1) than that for
the triplet state derived reaction (101 3 sec-1) (see next section for the origin of differences in the A factor).
While alkanones cleave from both S1 (np*) and T1 (np*) states, phenyl alkyl ketones cleave only from
T1 (np*). This behavior is consistent with the rapid rate of intersystem crossing from S1 to T1 for phenyl
alkyl ketones (101 1 sec-1; Figure 9.2).
51
Final 1.0, 4/13/2004
Table 9.5
52
Final 1.0, 4/13/2004
9. 20. A Model
We need a simple model that will answer the following questions: (a) Why is a-cleavage more
favorable from np* rather than pp* excited states? (b) Why does T1 (np*) react faster than S1 (np*)? (c)
Why is there a barrier for a-cleavage in the excited state? An orbital overlap model presented in Scheme 9.37
provides an answer for the different reactivities of np* and pp* excited states. In the np* state the carbonyl
oxygen has a single electron in the n-orbital, which lies in the plane of the a-bond. A p-type parallel
interaction between the singly occupied n-orbital and the doubly occupied s orbital of the a-C—C bond is
expected to weaken the a-bond and result in cleavage. Such an overlap results in a new p-bond and a pair of
radicals. In the pp* state the electrons are present in orbitals that are perpendicular to the a-bond, and no
overlap between p and s orbitals is possible. Therefore, the a-cleavge is unlikely to occur from pp* excited
state. This qualitative model does not explain the difference in behavior between the singlet and the triplet np*
states.
C—C s*
p*
R
R
C
R
C
O
n
C—C s
p
R
O
a-C—C
Note p*— s* interaction is not favored, they are perpendicular to each other.
Scheme 9.37
An insight into the mechanism can be obtained by inspection of the Salem diagram for the a-cleavage
process presented in Chapter 6. Basic conclusions drawn from the Salem diagram are the following: (a) At
the first level, the correlation diagram predicts that cleavage from both the np* singlet and triplet is disfavored.
Both correlate with a higher energy diradical species. (b) At the level where coupling between surfaces of the
same spin occurs, cleavage from the np* triplet state becomes allowed. In Figure x of Chapter 6 note that the
53
Final 1.0, 4/13/2004
triplet np* and pp* surfaces cross at a point slightly off from the vertical excited state.
Due to avoided
crossing between the triplet np* and the triplet pp* surfaces, cleavage from the triplet np* state becomes
possible. (c) The cleavage will have a barrier and its height is controlled by the point at which the triplet np*
and the triplet pp* surfaces cross.
According to the Hammond’s postulate this point will depend on the
energy gap between the triplet state and the product acyl and alkyl radical pair. The transition state would be
stabilized if the alkyl radical is more stable resulting in a lower activation energy.
(d) The only manner in
which the np* excited singlet molecule can reach the diradical species is via the pp* triplet surface, that is by
crossing from the singlet np* to the triplet pp* surface. Such a process is spin forbidden and is expected to
have a low probability. In other words the reaction will have a low A factor.
These predictions are consistent
with the experimental results presented in the previous section.
9. 21. Reactions of the acyl-alkyl radical pair
The final isolated product resulting from a- cleavage of a ketone depends on what type of reactions the
primary acyl and alkyl radical pair undergoes. The most common reactions of radical pairs produced from acleavage of dialkyl and alkyl aryl ketones are radical recombination, disproportionation, and decarbonylation
(Scheme 9.38). In the last case a new pair of radicals is formed, which may itself undergo radical
recombination and/or disproportionation.
Depending on the structure of a cyclic ketone two additional
reactions can occur: ring expansion to a carbene and rearrangment to a different diradical.
54
Final 1.0, 4/13/2004
O
recombination
(CH2)n
-CO
decarbonylation
O
CH2
+
(CH2)n
(CH2)n
CH(CH2)n-1CH 3
O
disproportionation
(CH2)n
H
CH2
(CH2)n
disproportionation
CO
(CH2)n
ring expansion
OR
CH3 ROH
O
O
(CH2)n CH3
OR
ROH
(CH2)n
n(H2C)
O
Scheme 9.38
Recombination: Recombination is a process in which the excited molecule fragments and recombines
in an energy wastage process. This process will be evident in the form of low quantum yield of a-cleavage
products and racemization and epimerization of the a-carbon (if an optically pure reactant ketone is involved).
Note that the primary radical pair formed from a triplet ketone would have triplet spin and would not recombine
within a ‘geminate cage’ unless it crosses to a singlet radical pair. Since the lifetime of a radical pair in
solution is too short lived for any intersystem crossing mechanism to operate, the recombination reaction
during a triplet reaction must occur from random free radicals and not from geminate triplet radical pairs.
Support for the recombination pathway during a-cleavage is found in the observation that, under
irradiation, the optically active ketone shown in Scheme 9.39 undergoes both disproportionation and
racemization. Racemization that occurs with very low efficiency can be completely suppressed by the addition
of radical scavengers such as dodecanethiol and stable nitroxide radical. Since the racemization is eliminated
55
Final 1.0, 4/13/2004
by very small amounts of the quenchers suggests that the recombination occurs between random free radicals
and not between geminate primary radical pair. This is consistent with the expectation that intersystem
crossing of the triplet radical pair to the singlet state requires much longer time (>10-6 sec) than the lifetime of a
solvent cage (<10-9 sec) in solution.
O
H
Ph
CH3
hn
OH
Ph
Ph
CH3
Ph
O CH2
Ph
Ph
disproportionation
PhCHO + PhCH
H
CH2
recombination with
racemization
O
O
hn
O
O
hn
O
O
Scheme 9.39
Disproportionation: Excitation of cyclopentanone and cyclohexanone results in ketene and enal
products, via disproportionation of the acylalkyl diradical. Along with disproportionation, recombination and
decarbonylation also occur. Idealized transition state geometries for the formation of ketene and enal products
from the acyl alkyl diradical are shown in Scheme 9.40. Although both ketene and enal formation involve
hydrogen abstraction at the diradical stage the sites involved are different for the formation of these two
products.
56
Final 1.0, 4/13/2004
O
O
hn
C
C=O
O
Scheme 9.40
Decarbonylation: The third typical reaction of acyl alkyl radical pairs is decarbonylation of the acyl
fragment. This reaction generally does not compete with recombination and disproportionation unless the
radical produced by decarbonylation is exceptionally stable (i.e., an allyl, benzyl or tert-butyl radical). For
example, irradiation of methyl tert-butyl ketone results mainly in formation of acetaldehyde and isobutylene
(disproportionation products), whereas irradiation of di-tert-butyl ketone results mainly in formation of
decarbonylation products (Scheme 9.41).
O
O
H
+
hn
O
+
H
O
O
hn
+
H
+ CO +
Scheme 9.41
57
Final 1.0, 4/13/2004
Rearrangement: If the acyl or alkyl fragments produced by a-cleavage are capable of rearrangement
(e.g., of the cyclopropyl carbinyl ~ homoallyl type), this process may compete with other reactions of the
diradical. One such example which involves two sequences of a-cleavage, ring opening, and cyclization is
provided in Scheme 9.42.
O
O
O
hn
a-cleavage
ring
opening
cyclization
O
O
O
hn
ring opening
and cyclization
a-cleavage
Scheme 9.42
Ring expansion to an oxacarbene: Ring expansion was first observed during the photolysis of bicyclic
ketones (Scheme 9.43). In this case the oxacarbene was trapped by various alcohols as well as cyclohexene.
Ring expansion occurs only when disproportionation and decarbonylation are disfavored or slow. As a result,
ring expansion occurs only with selected systems.
O
OR
ROH
O
hn
O
CHO
O
hn
+
O
R'OH
O
+
OR'
Scheme 9.43
58
Final 1.0, 4/13/2004
9. 22. Photochemistry of Cyclobutanones
The photochemistry of cyclobutanone and its derivatives is dominated by the primary photochemical
process of a-cleavage. Cyclobutanones undergo efficient a-cleavage from Sl (np*) to produce a singlet 1,4acyl-alkyl diradical, 1 D. From Scheme 9.44 it is clear that the fate of 1 D is very different from that of the 1,n
diradicals produced by photolysis of cyclopentanones and cyclohexanones. The latter compounds undergo acleavage predominantly via a Tl (np*) Æ 3 D process, and yield mainly disproportionation products (Scheme
9.40). The following reactions generally result from the 1,4-acyl-alkyl diradical: (a) decarbonylation, (b)
cycloelimination, and (c) oxacarbene formation (Scheme 9.44). Decarbonylation of 1 D produces 1,3-diradicals
which generally cyclize. The oxacarbene intermediate derived from 1 D has been trapped by alcohols.
+ CO
Decarbonylation
O
O
O
hn
S1(n, p*)
1D
Cycloelimination
CH2=C=O
CH2=CH2
Ring expansion
O
ROH
O
H
OR
Scheme 9.44
Another important difference between cyclobutanone photochemistry and that of larger cycloalkanones
is the observation of stereospecificity during the cleavage of the former. For example, the ethyl alkoxy
cyclobutanone A undergoes stereospecific decarbonylation to yield B, cycloelimination to yield C , and
oxacarbene formation to yield D (Scheme 9.45). Note in all cases the cis stereochemistry between the alkoxy
and the alkyl groups is maintained.
59
Final 1.0, 4/13/2004
O
S1(n, p*)
RO
1D
hn
-CO
O
hn
CH3OH
RO
O
CH2=C=O
+
+
RO
RO
A
OCH3
RO
B
C
D
Scheme 9.45
9.23. Chelotropic Decarbonylation Reaction
Not all a-cleavage process involves a radical pair or diradical intermediates. Concerted loss of carbon
monoxide from excited singlet state leading to stable products is known. Such reactions follow WoodwardHoffman rules. A few such examples are provided in Scheme 9.46.
O
hn
hn
O
O
O
O
hn
C6 H6
hn
O
Scheme 9.46
9. 24. Photochemistry of Dibenzylketones
60
Final 1.0, 4/13/2004
Dibenzylketone upon excitation undergoes decarbonylation to yield diphenylethane as the only
product. This reaction is very efficient (F=0.8).
When 1-(4-methoxyphenyl)-3-phenyl-2-propanone is
irradiated three products shown in Scheme 9.47 are obtained in the precise ratio of 1:2:1. The ratio remained
the same in various solvents whose viscosity changed between 0.56 (benzene) and 41.1cps (cyclohexanol).
This suggests that there is no geminate cage recombination in isotropic solvent media. Generation of aryl
acetyl radical has been established by trapping it with the nitroxide, a radical trap 2,2,6,6-tetramethylpiperidine1-oxyl. This observation is consistent with the suggestion that the decarbonylation proceeds by a two step
process (Scheme 9.47). Decarbonylation of the aryl acetyl radical is consistent with the behavior of di-tertbutyl ketone presented in Scheme 9.41.
OCH3
hu
H3CO
O
H3CO
H3CO
1 : 2: 1
AA + AB + BB
H3CO
O
H3CO
O
N
O
O
N
N
H3CO
O
Scheme 9.47
Photofragmentation of dibenzylketone upon direct excitation has been established to occur from
T1 (np*) states. Observation of a linear Hammett relationship between relative rates of a-cleavage and s+
values of the substituent suggests that the transition state for a-cleavage from the triplet state of dibenzyl
ketones has certain amount of ionic character (Figure 9.13). In this context it is interesting to note that while
1,3-diphenyl-2-propanone cleaves with a F of 0.7, 1,3-bis (4-cyanophenyl)-2-propanone does not cleave at all.
61
Final 1.0, 4/13/2004
The unexpected influence of substituent on the a-cleavage is consistent with the results of deoxybenzoins and
benzoin ethers discussed below.
pOMe
p-Me
Figure 9.13
pF
p-Cl
m-Cl
PhCH2COCH2Ar
hn
d
PhCH2CO
d
CH2Ar
PhCH2CO + CH2Ar
*
O
d
X
d
9. 25. Photochemistry of Deoxybenzoins and Related Systems
The key primary reaction deoxybenzoins and benzoin ethers undergo is the Norrish type I a-cleavage.
The radicals formed via this primary process are utilized to initiate polymerization.
62
Final 1.0, 4/13/2004
hu
O
X
O
O
X
O
X
X
X = p-CH3
k ~ 109sec-1
7
X = m-CF3 k ~ 10 sec-1
hu
O
O
X
O
O
X
X
X = OCH3
X = CN
k ~ 1010sec-1
k ~ 107sec-1
Scheme 9.48
O
hu
O
X
X
Figure 9.14
PhCOCH2Ar
hn
d
PhCO
d
CH2Ar
PhCO +
CH2Ar
*
O
d
X
d
63
Final 1.0, 4/13/2004
The rates of a-cleavage in deoxybenzoin derivatives, expectedly, increase upon substitution of a-hydrogens by
methyl groups (Scheme 9.49). The rates of a-cleavage for a number of aryl substituted deoxybenzoins in
benzene show a linear relationship (with s+ of the substituent) with a r value of –1.1. This observation plus the
fact that the p-methoxy enhances and p-cyano decreases the rate of a-cleavage are consistent with the model
that the transition state for a-cleavage has the structure shown in Figure 9.14. This proposal is also supported
by three orders of difference in the rate between a-cyano (2.2 x 107 sec-1) and a-methoxy (>101 0 sec-1)
substituted deoxybenzoins. Since no evidence for ionic intermediate is available, one need to conclude that the
heterolytically inititated cleavage process leads to a radical pair via an internal electron transfer process.
Further experiments are needed to fully understand this process.
O
Ph
X
R R'
O
hu
Ph
R
X
R'
X = Ph; R = R'= H
ka = 0.16 x 107 sec-1
X = Ph; R = H; R'= CH3
ka = 2.1 x 107 sec-1
X = Ph; R = R'= CH3
ka = 12 x 107 sec-1
X = R = H; R'= CH3
ka = 1.1 x 107 sec-1
Scheme 9.49
9. 26. Reluctant a-Cleavage Reactions
We learnt that a-cleavage is either slow or non-existant in systems whose triplet energy is lower than
the energies of the product radical pair. Such systems when excited to upper excited states do undergo acleavage. Two experimental strategies have been used to achieve a-cleavage in such reluctant systems.
TWO LASER (TWO COLOR) FLASH PHOTOLYSIS: In the two laser (two color) technique, two lasers of
different wavelengths, firing sequentially, are employed to produce the upper states of molecules. The first
laser produces the lowest excited state of the molecule and the second laser selectively excites these molecules
64
Final 1.0, 4/13/2004
into an upper level. By this approach a variable delay can be introduced between the two photons to allow the
lower excited state concentration to build up.
By using a tunable laser the wavelength of the second photon
can be adjusted to correspond to the absorption maximum of the lower excited state. Since excited singlets
(S1) are too short lived in comparison with the laser pulse duration to allow for efficient upper singlet
production, the two laser set up is better suited for populating upper triplets than upper singlets.
An illustration of the above technique is found in the cleavage reaction of benzil (Scheme 9.50).
Benzil does not cleave when populated to the T1 (pp*) state by either direct excitation or triplet sensitization.
However, generation of a higher triplet through excitation of T1 results in a-cleavage.
O
2 photons
O
2
O
O
2 photons
2
Scheme 9.50
LASER JET EXPERIMENTS: The two laser (two color) technique described above provides excellent
spectroscopic information on the transients produced during the formation of products from upper excited
states. However, isolation of the products of a photoreaction by this approach could be tedious. For product
isolation ‘laser jet’ apparatus is often used. In this laser jet technique, a high velocity microjet of a solution of
material to be irradiated is injected into the focal region of an argon ion laser beam. The typical microjet flow
rates can be controlled and the sample recycled as many times as necessary to bring the reaction to completion.
Consequently, isolation of significant quantities of products is possible. Usually a high intensity CW argon
ion laser is used to excite molecules. In this method sufficient concentrations of molecules in their S1 or T1
states are trapped within a ‘microbubble’ so that they can absorb a second photon. Reactions generally occur
65
Final 1.0, 4/13/2004
from the upper excited states. Structural and electronic details of the state from which the reactions occur are
often lacking. The ketone A shown in Scheme 9.51 is stable to low intensity light (Rayonet Reactor).
However when irradiated with an Argon ion laser under laser jet conditions it yields the product shown in
Scheme 9.51 believed to be derived via Tn.
Ph
Ph
O
Ph
nhn
Ph O
C
Ph
hn
-CO
Ph
Ph
Ph
Ph
+
A
Scheme 9.51
66
Final 1.0, 4/13/2004
9.27. b-Cleavage
The np* excited states (singlet and triplet) of conjugated cyclopropyl ketones commonly undergo
homolytic cleavage of a b-bond (Scheme 9.52). A model that can be used to rationalize this reaction shown in
Scheme 9.53 involves overlap of the singly occupied p* orbital (C=O) with the s* orbital of the b-bond.
Since the cleavage is initiated by the interaction between p* and s* orbitals the reaction could occur from
either np* or pp* states.
O
O
O
-H
hn
H
Scheme 9.52
s*
p*
C
n
s
b C—C
p*
O
n
C=O
p
s*
p*
H
H
n
C=O
p
pp*
np*
s
b C—C
Scheme 9.53
If two bonds are potentially available for cleavage, the bond capable of best overlap (based on energy
matching and geometry) with the p* orbital will be cleaved preferentially. For example, the photochemical
interconversion of cis and trans-5,6-diphenylbicyclo[3.1.0]hexanones shown in Scheme 9.54 can be
accounted for by b-cleavage of any of the three bonds, marked a, b or c. Cleavage of ‘c’ is unlikely as it is
neither a nor b bond. However both ‘a’ and ‘b’ are b-bonds and both are likely to cleave. In the case of an
optically pure trans isomer cleavage of either one of them would yield the same product (cis isomer) but their
stereochemical implications would be different (Scheme 9.54). As shown in the scheme products are
67
Final 1.0, 4/13/2004
enantiomers. It has been shown that only one of the two enantiomers, A alone is obtained upon photolysis of
the optically pure ketone. Preferential cleavage of ‘a’ can be rationalized on the basis that it is the one with
which the p* orbital overlaps best (Scheme 9.54).
O
H
O
O
Ph
Ph
H
Ph
Ph
H
Ph
Cleavage of bond 'a'
O
O
hn
b a
Only
Ph
Ph
Ph
Ph
Cleavage of bond 'b'
O
O
H
O
Ph
Ph
H
Ph
H
Ph
Ph
Cleavage of bond 'b'
Scheme 9.54
If the p* orbital indeed assists in cleaving the b-bond of cyclopropanes, cleavage of epoxides should
occur even more easily, since the s* orbital of the epoxide C—O bond is expected to be lower in energy than
the corresponding cyclopropyl orbital. The photoisomerization of benzalacetophenone epoxide to
dibenzoylmethane has been known since 1918 (Scheme 9.55). A fission of the Ca—O bond of the epoxide
ring, followed by a 1,2-H shift, explains the 1,3-diketone formation.
68
Final 1.0, 4/13/2004
H
C 6H 5
C
H
Cb
Ca
O
H
hn
C 6H 5
C 6H 5
H
C
Ca
Cb
O
O
hn
hn
O
C 6H 5
O
O
O
O
Scheme 9.55
9.28. b-Cleavage resulting in loss of a-substituents
A number of a-substituted carbonyl compounds suffer the loss of the a-substituent upon excitation.
The a-substituents that have been established to cleave are acetoxy, sulphonyloxy, phosphate esters, halogens,
N,N-dimethylamino, sulphonium, alkyl sulfide, alkyl sulfoxide and sulfone groups (Scheme 9.56).
The b-
cleavage of phenacyl alkyl sulfides is extremely rapid, kb~108 s-1 and the rate is independent of the nature of the
lowest excited state (np* or pp*). For example, the rates of cleavage for para-cyano phenacyl phenyl sulfide,
para-methoxy phenacyl phenyl sulfide and phenacyl tert-butyl sulfide are nearly the same (~108 s-1).
Depending on the leaving group the cleavage could be either homolytic or heterolytic. One could visualize the
b-cleavage of the above substituents as being facilitated by the overlap of p* orbital of the carbonyl and the s*
orbital of the C—X groups (similar to the one in Scheme 9.53).
O
Ph
O
hn
CH2X
Ph
X
O
Solvent
CH2
Ph
CH3
X = Cl; S(CH3)2 BF4; OCOCH3; OPO(OR)2; SPh;
Scheme 9.55
69
Final 1.0, 4/13/2004
9.29. Benzoin Esters and Related Systems
Although based on the behavior of deoxybenzoins and benzoin ethers, a-acetoxybenzoins (see section
9.25) would be expected to undergo a-cleavage, they preferentially undergo b-cleavage. The b-cleavage is a
general reaction with benzoins having a-substituents that can be easily lost as an anion. Following the release
of the a-sbustituent deoxybenzoin cyclizes to 2-phenylbenzofuran (Scheme 9.56). The extent of 2phenylbenzofuran formation is dependent on the a-substituent. For example, while chloro substituent gives
only 1% of 2-phenylbenzofuran, dimethylamino hydrochloride substituent yields the furan in 54%. Being a
triplet reaction (np* or pp*), the cation that results following anion loss must remain in the triplet state, i.e., the
reaction must be adiabatic in character (Scheme 9.57). Although the mechanism of these reactions has not
been investigated, a triplet a-keto cation has been spectroscopically characterized and chemically trapped with
trifluroethanol during the photolysis of benzoin diethyl phosphate in water (Schemes 9.58 and 9.59). In the
absence of the trapping agents the excited a-keto cation probably cyclizes to yield the benzofuran. This
mechanism for the b-cleavage operates only in water and very polar hydroxylic solvents. The overall
When X can be lost as an
anion b-cleavage occurs.
X
hn
O
O
X = Cl
Better the anion as the
leaving group faster the bcleavage.
1%
X = OCOCH3
15%
X = N(CH3)2. HCl
54%
Scheme 9.56
R
R
Ph
Scheme 9.57
O
Ph
Ph
O
Ph
pp*
pp*
70
Final 1.0, 4/13/2004
O
O
+
O
H2O / CF3CH2OH
P (OEt)2
OH
O
O
OEt
CH2CF 3
hn
P
O
OEt
O
O
CH3CN
+
OEt
P
HO
OEt
Scheme 9.58
O
Ph
O
3
O
hn
Ph
O
ISC 3
A
O = P - OEt
-PO(OEt)2OH
CF3CH2OH
O
H
Ph
Ph
OCH2CF3
H
Ph
Ph
Ph
OEt
O
Ph
Scheme 9.59
.
9. 30. Addition to olefins
Photoaddition of olefins to carbonyl compounds was discovered at the turn of the 20th century.
This
addition generally yields a product known as an oxetane, and the reaction is termed the Paterno-Buchi reaction
to recognize the two chemists who played key roles in its development (Scheme 9.60). These additions are
triggered by the excitation of the carbonyl chromophore to an excited state. The olefin reacts from its ground
state. All three types of ketones - dialkyl, aryl alkyl and diaryl- as well as aldehydes undergo this reaction.
Addition occurs to electron-rich and electron-poor olefins, acetylenes and allenes.
71
Final 1.0, 4/13/2004
O
O
hn
+
Ph
Ph
H
Ph
O
Ph
H
H
H
O
O
H
Ph
Ph
+
C
hn
H
Ph
Ph
Ph
O
Ph
hn
O
hn
+
O
hn
H
H
H
O
O
Ph
H
+
O
Ph
O
H
Scheme 9.60
9. 31. Addition to electron-rich alkenes: Reactive state
Irradiation of acetone in presence of either cis-1-methoxybutene or trans-1-methoxybutene gives four
isomeric oxetanes (Scheme 9.61). An indication that acetone adds to enol ethers from two different excited
states is provided by the observation that the ratio of the isomers is dependent on the concentration of the olefin
used. For example at low concentrations of cis -1-methoxybutene (extrapolated to zero) the ratio of oxetane A
and B is 1.06 and at high concentrations it is 2.5.
The difference in selectivity between high and low
concentrations is an indication that two reactive states with different lifetimes are involved in the addition
(Chapter 8). Lower concentrations trap the state with longer lifetime (T1), while higher concentrations are
required to trap the state with shorter lifetime (S1). While dialkyl ketones add to alkenes from both S1 and T1,
expectedly, aryl substituted ketones and aldehydes react only from T1.
72
Final 1.0, 4/13/2004
CH3O
(CH3)2CO
H
+
C
C
H
C2 H5
hn
CH3
O
CH3
C2 H5
OCH3
H
H
A
O
+
CH3
H
CH3
CH3
CH3
O
+
CH3
H
OCH3
H5 C2 H
B
CH3
H
H
CH3O
O
+
CH3O
C2 H5
C
C2 H5
H
D
hn
H
(CH3)2CO
+
H
C
CH3O
C
C2 H5
Scheme 9.61
9. 32. Addition to electron-rich alkenes: Diradical intermediates
The addition of triplet excited ketones (dialkyl ketones as well as aryl substituted ketones and
aldehydes) to electron rich olefins such as enol ethers and alkyl substituted olefins involves an intermediate as
indicated by several factors.
First, the addition is not stereospecific, meaning there is a step in which the
stereochemistry of the incoming alkene is lost. Second, the recovered olefin is geometrically isomerized,
suggesting that there is an intermediate formed that reverts to starting material with loss of olefin
stereochemistry. Since the triplet energy of enol ethers and alkyl substituted olefins is well above that of
acetone, a triplet-triplet energy transfer mechanism cannot be responsible for the geometric isomerization of the
olefins. Third, with certain olefins, side products are observed. For example, in the case of acetone and
tetramethylethylene, biradical disproportionation products are formed in addition to oxetane (Scheme 9.62).
Yet another observation that supports the involvement of an intermediate is the isolation of a rearranged product
73
Final 1.0, 4/13/2004
during the addition of benzophenone to vinyl cyclopropane (Scheme 9.63). Diradical intermediate accounts
for the observed rearrangement.
O
O
O
+
coupling
20%
n, p*
disproportionation
O
+
O
8%
8%
Scheme 9.62
O
O
Ph2C
O + CH2
hn
C
Ph
Ph
Ph
Ph
H
65%
Ph
O
Ph
Ph
O
Ph
15%
Scheme 9.63
The above results are understandable in terms of a mechanism in which reaction between Tl and an
electron-rich olefin leads to a triplet diradical (3D). Similar diradical mechanism is likely during the addition of
excited singlet dialkyl ketones to electron rich olefins. In this case a singlet diradical (1D) would result. Of the
two diradicals, 3 D is expected to have a longer lifetime and thus would be expected to suffer greater
stereochemical loss compared to 1 D. As a result, oxetane formation is expected to be more stereoselective from
Sl than from T1 . The reaction is unlikley to be stereospecific from both S1 and T1 states since the olefin
74
Final 1.0, 4/13/2004
addition to the n-orbital yields a 1,4-diradical in which the resulting two p-orbitals are perpendicular to one
another (similar to the one obtained during g-hydrogen abstraction) and must undergo bond rotation prior to
ring closure. As indicated above, the ratio of the two oxetanes is dependent on the enol ether concentration and
at higher concentration when the S1 state will be captured by the olefin the addition is more stereoselective. A
confirmation for the involvement of a diradical during the addition of ketones (triplet) to electron rich olefins
comes from flash photolysis studies. A direct detection of the 1,4-diradical has been made during the addition
of benzophenone and xanthone triplets to 1,4-dioxene and benzophenone to tetramethylethylene.
The involvement of diradical as an intermediate also accounts for the exo-endo selectivity observed
during the addition of various aldehydes to the electron rich olefin 2,3-dihydrofuran (Scheme 9.64).
The
reaction occurs mainly from the triplet state and the main product (>98%) is the one predicted based on radical
stability. This product can exist in two arrangements, exo and endo (Scheme 9.64), of which the former less
sterically hindered product is thermodynamically more stable. As illustrated in Scheme 9.64, the endo/exo
ratio depends on the steric properties of the aldehyde. Bulkier aldehydes give higher endo selectivity. How
can a diradical intermediate account for this counter-intuitive results?
R
H
O
hn
+ RCHO
O
O
R
+
benzene
O
H
Endo
R=
H
endo : exo
O
H
Exo
R=
endo : exo
methyl
45 : 55
phenyl
88 :12
ethyl
58 : 42
o-tolyl
93 : 7
isobutyl
67 : 33
mesityl
> 98 : 2
Scheme 9.64
75
Final 1.0, 4/13/2004
R
1
endo
H
O
k ISC A
A
X
3
O
H
H
X
k ISC B
H
3
A
R
1
B
exo
B
Scheme 9.65
A closer look at the triplet diradical that is formed after the initial addition of furan to triplet
benzaldehyde (Scheme 9.65) provides an answer. The two conformations of the triplet diradical are shown in
Scheme 9.65; closure of (B) will yield the thermodynamically more stable exo isomer, while A produces the
endo isomer.
Note that the two p-orbitals of the diradical are perpendicular to each other (as a result of
addition of n-orbital to the p-bond of the olefin) and this geometry as per Salem rules (Chapter 6) is ideal for
intersystem crossing. The precursor diradical B that yields the thermodynamically more stable exo isomer is
sterically more hindered and is expected to be present in a lesser amount in the equilibrium. Since 1 D will
close to the oxetane as soon as it is formed, the final product distribution is a reflection of the distribution of
the conformers in the 3 D state rather than the stability of the final product.
9. 33. Addition to electron-rich alkenes: Involvement of exciplex
Indirect evidences in favor of triplet exciplex during the addition of diaryl ketones to electron-rich
alkenes have been provided: (a) During the addition of benzophenone triplet to cis or trans-2-butene no 2 Hisotope effect was observed. This suggested that the primary photoreaction is not bond formation to give the
1,4-diradical intermediate. (b) The rate of phosphorescence quenching of 4-carboxymethyl-benzophenone
triplet by alkenes showed a linear relationship with the ionization potential of the latter. For example, while 1hexene quenched the triplet at a rate of 7.1x106 M-1s-1, 2,3-dimethyl-2-butene quenched it at a rate of 1.6x109
M-1s-1. The rates of quenching of acetone S1 and T1 by electron rich alkenes correlate linearly with the
76
Final 1.0, 4/13/2004
ionization potential of the alkene, providing additional information that during the acetone–alkene interaction,
the alkene acts as an electron donor and the excited acetone as an acceptor. In highly activated ketones such as
quinones an ion pair intermediate has been detected detected by time resolved CIDNP and time resolved
transient spectroscopy. Thus addition of excited ketones and aldehydes to olefins may result in an exciplex, an
ion pair and/or diradicals.
9. 34. Addition to electron-rich olefins: Regioselectivity
The addition of electron rich olefins to excited np* carbonyls consists of the following steps (Scheme
9.66): (a) The first step is the nucleophilic attack of the filled p-orbital of the electron rich olefin on the excited
carbonyl oxygen (n-orbital) to form an exciplex. (b) The attack results either in full or partial electron transfer
to generate a radical ion pair. (c) The ion pair or exciplex combines to form a C—O bond resulting in a
diradical intermediate. (d) The diradical, if triplet, lives long and undergoes other reactions before crossing to
the singlet state. (e) Finally the singlet diradical closes to yield the oxetane.
O
R
R
O
R
R
O
R
O
R
Exciplex
+
R
R
O
O
R
R
R
+
R
O
R
R
Scheme 9.66
The above addition can be understood on the basis of the orbital interaction diagram provided in
Scheme 9.67. This correlation requires that the filled HOMO of the alkene (p) must interact with the partially
occupied n orbital of acetone. Such an interaction requires that the alkene approach the excited acetone along
77
Final 1.0, 4/13/2004
the n-orbital (Scheme 9.67). This geometry of approach is called the ‘perpendicular’ approach. This has been
supported by the variation in the fluorescence quenching rate between several norbornyl ketones (Scheme
9.68). When the approach to the n-orbital is restricted by the bulky methyl groups, the rate of quenching is
decreased.
Perpendicular approach
Parallel approach
C
C
O
O
n
p*
p
p*
C
C
C
C
C
C
C
C
D
p* LUMO
LUMO
C
C
LUMO p*
p*
A
p HOMO
n
D
HOMO
C
C
HOMO p
C=C
A
D
C=C
A
electron-deficient
alkene
A - electron acceptor
C = O*
np*
electron-rich
alkene
D - electron donor
Scheme 9.67
78
Final 1.0, 4/13/2004
Fluorescence Quenching of 2-Norbornanone
Singlets by trans-DCE and cis-DEE
k qr x 10 -9 [M -1 sec -1]
p-orbital attack
n-orbital attack
NC
EtO
CN
5.1
O
OEt
O
"faces"
"edges"
1.2
OR
O
CN
O
O
FAST
1.0
SLOW
1.5
O
O
0.48
O
OR
O
CN
< 0.03
SLOW
FAST
Schematic of the use of substituent effects on the rate of quenching of norcamphor and its derivatives by electron-rich
(enol ethers) and electron-deficient (cyanoethylenes) to demonstrate "edge" (n-p interaction) and "face" interactions of
the n,p* state and ethylenes.
Scheme 9.68
Regiochemistry of addition is expected to depend upon whether the interaction between the n-orbital of
the carbonyl and the p-orbital of the alkene leads to a diradical or a radical ion pair. Two examples of addition
of electron rich alkenes to acetone provided in Schemes 9.69 and 9.70 highlight this point. Both additions
involve diradical intermediates. However, while the addition of acetone to 2-methylpropene is regioselective
and it can be predicted on the basis of radical stability that to enol ethers is not regioselective. In the latter case,
although isomer A usually predominates, the selectivity is less than what might be expected on the basis of
diradical stability. Obviously, diradical stability is not of paramount importance in this case. It is quite likely
that the regiochemistry of oxetanes is decided prior to formation of diradical intermediate.
Possibly in this
electron rich olefin electron transfer precedes the bond formation. Under such conditions the bond formation
will be dictated by the orbital coefficients of the interacting orbitals of the radical ion pair. The addition may be
considered as a nucleophilic attack by the filled n-orbital of carbonyl oxygen on the singly occupied p-orbital
79
Final 1.0, 4/13/2004
of the olefin radical cation. The orbital coefficients of the olefin radical cation provided in Scheme 9.71 nicely
accounts for the absence of regioselectivity in this case. Thus it is clear that in order to accurately predict the
regioselectivity during oxetane formation one needs to know whether electron transfer or carbon oxygen sbond formation is the primary step. It is important to recognize that there are a number of examples where
excellent regioselectivity has been achieved ( Scheme 9.72).
CH3
O
hu
Ph2CO + (CH3)2C=CH2
CH3
O
Ph
CH3
+
Ph
Ph CH
3
Ph
less stable
more stable
CH3
O
Ph
CH3
O
CH3
+
Ph
Ph CH3
Ph
90%
10%
Scheme 9.69
O
hu
+
n, p*
OR
O
O
OR
E
O
+
OR
OR
D
OR
O
+
O
OR
60%
40%
Scheme 9.70
80
Final 1.0, 4/13/2004
Comparison of Charge Distribution at the Ethylenic Carbons
for the Ground State and Radical Cation of a 1,1-Dialkoxyethylene
(CH3)2C
(CH3)2C
O*
+
CH2
biradicals, etc.
+
C(OR) 2
31
O
[CH2
14
C(OR)2]
34
32
Scheme 9.71
O
Ph
hn
+
Ph
SiMe 3
O
+
Ph
SiMe 3
Ph
SiMe 3
O
Ph
Ph
24 : 1
CH3
O
+
Ph
Ph
hn
CH3
OTMS
O
Ph
+
OTMS
O
OTMS
Ph
Ph CH3
Ph
94 : 6
Ph
SMe
H
O
Ph
+
hn
H
SMe
O
Ph
H
SMe
+
O
H
Ph
Ph H
Ph H
100 : 0
Scheme 9.72
81
Final 1.0, 4/13/2004
9. 35. Addition to electron-deficient alkenes
Results from photocycloaddition of ketones to electron-poor alkenes such as cyanoethylenes (Scheme
9.73) contrast sharply with those for photocycloaddition of ketones to electron-rich ethylenes: (a) Only Sl (np*)
forms oxetanes with cyanoethylenes. (b) Quenching of S1 (np*) does not cause cis-trans-isomerization of the
alkene as a side reaction. (c) Quenching of Tl (np*) sensitizes cis-trans-isomerization of the cyanoethylene but
does not lead to oxetane. (d) Oxetane formation from S1 (np*) is stereospecific. (e) Oxetane formation from S1
(np*) is regiospecific, but the product structure does not conform to that expected from the most stable diradical
rule based on attack on the carbonyl oxygen.
CN
O
(CH3)2C
O
+
CN
S1(n, p*)
CN
stereospecific
CH3
CH3
CN
CH3
O
CN
(CH3)2C
O
+
CH3
S1(n, p*)
CH3
CN
regiospecific
CH3
CN
(CH3)2C
O
T1 (n, p*)
(CH3)2C
T1 (n, p*)
O +
(CH3)2C
+
CN
+
O
CN
CN
cis-transisomerization
CN
(CH3)2C
O
CH3
+
CN
CN
dimerization
Scheme 9.73
Rates of quenching of S1 (np*) of acetone by several electron deficient alkenes generally increases as
the electron affinity increases. The relationship between rate of quenching and the electron affinity of the alkene
suggests that the excited acetone acts as the electron donor and the alkene as the acceptor. Note that the roles
of the excited carbonyl and the alkene are reversed compared to the situation with electron rich alkenes. For an
82
Final 1.0, 4/13/2004
excited carbonyl to act as an electron donor the alkene has to approach the ketone along the p-face. This
approach is called the ‘parallel’ approach.
This geometric preference is supported by the variation in
quenching observed when the p-face of the ketone is blocked (Scheme 9.68). The rate of quenching is
reduced by substituents that block access to the p-face of the carbonyl group. The orbital interaction between
the np* ketone and electron poor alkenes is shown in Scheme 9.67. In this case the interaction occurs
between the p* (LUMO) of the carbonyl and the p* (LUMO) of the alkene.
A number of indirect lines of evidence indicate that exciplexes may act as intermediates during oxetane
formation between acetone and electron-poor alkenes: The fact that np* states (S1) may be completely
quenched by ethylenes but generally lead to products with much less than 100% efficiency is consistent with
the presence of a deactivation channel (an intermediate that can lead to the reactants without bond formation) to
the ground state along the pathway to the product. For example the quantum yield of oxetane formation
between 1 acetone* and 1,2-dicyanoethylene is only 0.1 although the excited singlet is quenched almost at
diffusion controlled rate (5x109 M-1s-1). The fact that the rate constants for quenching are much higher than
those predicted from simple radical addition is inconsistent with the direct primary formation of diradical
intermediates in the quenching step. A linear relationship between the quenching rate constant and the electron
affinity of the alkene suggests a charge transfer interaction between the alkene and the excited ketone. The
above data suggest that a charge transfer complex (exciplex) or a D± (radical ion pair) may precede the product
formation.
Let us consider the regiochemistry of addition of acetone to a-methyl acrylonitrile. Four different
diradicals are possible in the addition of acetone np* singlet to a-methyl acrylonitrile (Scheme 9.74). If
diradical stability controls the regiochemistry, isomer B would be predicted to be formed. But the isolated
isomer is A. Obviously the regiochemistry is decided prior to diradical formation and the stability of diradical
has no role to play in this step. Salem diagram discussed in Chapter 6 correctly predict the regichemistry of
addition.
83
Final 1.0, 4/13/2004
O
CN
E
(CH3)2C
S1(n, p*)
O +
CH3
CN
O
O
CN
O
CN
O
CN
A
CN
B
D
C
O
not formed
CN
F
Scheme 9.74
Salem diagrams for the formation of the two diradicals, precursors to oxetanes E and F (Scheme 9.74)
are shown in Figure 9.15. Correlation diagram is drawn for two approaches, perpendicular and parallel
approaches (Scheme 9.67). The parallel approach applies to electron deficient olefins and perpendicular
approach to electron rich olefins. While addition to carbon is allowed that to oxygen is forbidden from excited
np* state. During the addition to oxygen the energy increases from both np* singet and triplet. On the other
hand addition to carbon smoothly leads the diradical A. Therefore independent of the stability of the two
diradicals A and C, A alone is favored to be formed which explains the formation of the unexpected oxetane
based on the behavior electron rich alkenes. Reaction that is favored from S1 is expected to be inefficient due
to the presence of a ‘hole’ (avoided crossing) in the excited state surface. This prediction is consistent with the
experimental obervation. In spite of all the S1 being quenched by 1,2-dicyanoethylene, only 10% of it yield the
oxetane.
84
Final 1.0, 4/13/2004
Figure 9.15
9. 36. Diastereoselective and enantioselective addition of alkenes
Paterno-Buchi reaction of benzaldehyde under normal conditions would proceed equally from the two
prochiral faces of the carbonyl chromophore. If one wishes to control the addition, the olefin should be able to
to distinguish the two faces. Two approaches have been used to achive this goal. In one a chiral auxiliary is
covalently linked to the alkene and in the other a template is used to block one face of the carbonyl
chromophore. Addition of phenyl glyoxalate to various alkenes serves as an example of how a chiral auxiliary
may influence an oxetane formation. The menthyl derived chiral auxiliaries were localized in the keto ester
part and thus relatively far from the reaction site. In all cases, independent of the structure of cycloalkene and
the ester substituent, exclusively the endo phenyl distereomers were formed (Scheme 9.75). Importantly the
remote chiral auxiliary steered the addition mostly towards a single diasteromer (d.e. in the case of 8-phenyl
menthyl substituted: 96%). Ability for the alkene to distinguish the two faces arises from the steric blocking of
one face by the chiral group (Scheme 9.76).
85
Final 1.0, 4/13/2004
O
O
Ph
COOR*
O
O
hn
+
O
O
Ph
Ph
+
O
O
CO2 R*
R*O2 C
R*
(-)-8-Ph-Menthyl
(-)-Menthyl
O
de
> 96%
57%
Scheme 9.75
One face of carbonyl blocked by the menthyl
group
Ph
O
O
O
Ph
OCH3
Ph
O
O
Scheme 9.76
In the second approach, the alkene is steered to approach the carbonyl preferentially from one face by
the use of external forces. The example shown in Scheme 9.77 illustrates this concept.
The alkene,
dihydropyridone when pre-associated to the carbonyl with the help of hydrogen bonding to the chiral amide the
addition selectively occurs from one face. A diastereomeric ratio of 95:5 is achieved in toluene while that in
acetonitrile is 50:50. Importance of pre-organizing the dihydropyridone prior to exciting the carbonyl is
evident from the fact that when the chiral amide is modified (R=CH3 ) so that it can not form hydrogen bond
with the dihydropyridone the diastereomeric ratio is 50:50.
86
Final 1.0, 4/13/2004
O
O
O
hn
H
O
O
N
+
H
O
NR O
O
O
O
N
H
NR
O
O
N
H
O
NR
O
O
O
R=H
acetonitrile
benzene
toluene
50/50
83/17
95/5
R = CH3
benzene
50/50
H
O
N H
H N
O
O
O
Scheme 9.77
9. 37. Intramolecular photocycloaddition
Similar to intermolecular addition of excited carbonyl to alkene, intramolecular oxetane formation is
also known. The mechanism for intramolecular addition is exactly the same as the ones for intermolecular
addition. Enones where the ‘ene’ and ‘one’ parts are separated by more than two carbons readily undergo
intramolecular oxetane formation without any complications due to side reactions (Scheme 9.78, eqs. 1-3).
Even systems where the alkene and the carbonyl chromophores are separated by 15 atoms (including the aryl
ring) undergo intramolecular oxetane formation. One such example involves the addition of alkene to
benzophenone both connected by a methylene chain (Scheme 9.78, eq. 4).
87
Final 1.0, 4/13/2004
O
O
O
hn
+
(1)
2:5
O
O
hn
O
(2)
O
O
O
(3)
hn
(CH2)9
O
O
hn
C
O
O
(CH2)9
C
O
(4)
O
Ph
Scheme 9.78
9.38. Synthetic applications of photoreactions of carbonyl compounds
Several reactions we have learnt in this chapter have been utilized during synthesis of complex organic
molecules. Without going into the details the reaction involved and the molecule being synthesised are
highlighted with selected examples below.
Intramolecular d-hydrogen abstraction has been used repeatedly with significant success (yiled>65%)
during the synthesis of dodecahedrane (Scheme 9.79). Synthesis of pharmaceutically important estrone has
been achived through the use of Norrish-Yang reaction (Scheme 9.80). In this case the photoenol formed via
88
Final 1.0, 4/13/2004
g-hydrogen abstraction is intramolecularly trapped to build a steroidal skeleton. Overall yield of the
photochemical step is 45%.
O
HO
H CH OPh
2
CH2OH
(1) hn
(2) Li, NH3
R
(3) H+
R
OH
O
hn
dodecahedrane
Scheme 9.79
O
O
hn
OH
O
H
H
MeO
MeO
[61 %]
O
O
H
H
H
OH
H
MeO
H
O
HO
( + )-estrone
H
OH
H
MeO
Scheme 9.80
89
Final 1.0, 4/13/2004
The first total synthesis of (±) asteltoxin, inhibitor of oxidative phosphorylation, makes use of the
Paterno-Buchi reaction between 3,4-dimethylfuran and b-nezyloxypropanol (Scheme 9.81). Syntheses of
several pheromones and insect sex attractants have utilized the Paterno-Buchi reaction. One such examples is
provided in Scheme 9.82. Intramolecular Paterno-Buchi reaction of 2-allylcycloheptanone serves as a simple
route to azulene (Scheme 9.83).
Me
Me
Me
H
OBn
+
O
O
O
OBn
Me
hn
O
H
(63%)
Bn = CH2Ph
OH
OH OH
O
O
O
O
asteltoxin
OMe
Scheme 9.81
H
O
O +
+
H
H
H
H
O
O
H
OH
Fruit Fly Attractant
Scheme 9.82
90
Final 1.0, 4/13/2004
O
O
hn
H
D
OH
+
Scheme 9.83
The oxacarbene generated via Norrish type I cleavage has been utilized during the synthesis of prostaglandins
and analogues (Scheme 9.84), the natural product muscarine (Scheme 9.85), and thromboxane analogues
(Scheme 9.86).
OH
O
OH
O
hn
R'
Wittig
H2O
R
R
OH
HO
R
Prostaglandin F2a
OH
R' =
R=
COOH
OH
Scheme 9.84
Me
OSiMe2tBu
O
hn
Me
CH2Cl2
H
O
OMe
4 steps
Me
O
+
NMe3
-78o
t
BuMe2SiO
HO
Muscarine
Scheme 9.85
91
Final 1.0, 4/13/2004
O
H
H
(CH2)6CO2Me
11 steps
R
HO
CH3
HO
1
R1
O
OR2
Me
hn, MeOH
(CH2)6CO2Me
MeO
O
R1
thromboxane analogue
Scheme 9.86
9.39. Norrish type I reaction utilized in photoimaging
Photoimaging is a technique used for capture and replication of image information which utilize
photons. This technique is employed in photography, office copying, printing business, in the manufacture of
printed circuit boards and printing plates and in the generation of holographic images. Figure 9.16 diagrams
the imaging steps and illsutrates the process application for the preparation of two representative kinds of
images. All photoimaging processes can be reduced to three elementary steps: image capture, image rendition
and image readout. The fundamental photochemistry of the imaging system resides in the image capture step.
A final photoimage will result only if the light-struck regions of the light sensitive medium can be differentiated
from the unexposed regions.
One process used in the imaging technique is photopolymerization.
Photopolymerization is the generic process of converting small molecules into larger ones triggered by light.
The imaging is created with the help of a mask that controls the area that is exposed to light. Once the light
exposed and light unexposed areas are differentiated through monomer-polymer compositions a permanent
image can be created through furtheer processing. Two ingredients play an important role in the imaging
process i.e. monomer and light sensitive initiator. The photoinitaor generates free radicals that initiates
polymerization in the light exposed area.
92
Final 1.0, 4/13/2004
Figure 9.16
Many photoinitiators used in imaging industry are molecules that we have come across (Scheme 9.87)
in this chapter. These molecules undergo a-cleavage upon exposure to light. The primary radicals produced
by a-cleavage or the secondary radicals formed from the primary radicals initiate polymerization of the
monomer coated onto a support.
Initiator is a key component that creates a permanent image although
superior processing and other manipulations lead to a saleable product.
O
OCH3
C
C
hn
O
OCH3
C +
C
O
H3CO
OCH3
OCH3
CH3
O
O
O
+
H
O
H OCH3
CH3
O
O
O
C2H5
CH3
C2H5
O
CH2
O
O
CH3
HO
CH3
H5C2
N
HO
N
CH3
H3C
O
Photoinitiators
Scheme 9.87
93
Final 1.0, 4/13/2004
9.40. Phototriggers and photoprotecting groups: b-Cleavage reaction exploited
The physiological investigation of neuronal circuits and behavior of living brain slices frequently
demand a fast and focal administration of bioactive substances. Traditionally, this has been accomplished with
pressure injections or ionophoresis. During the last few years, photolysis of ‘caged’ compounds has become
an increasingly viable alternative to these traditional methods. Caged compounds are comprised of bioactive
molecules that are covalently bound to a photoabsorbing group that results in a photolabile, inactive ‘caged’
molecule. Upon UV illumination, the photolabile caged compound is cleaved into a free biologically active
molecule and the free caging group. This process is termed triggering. Ideally a phototrigger (photoactive
compound + biactive compound) should be biologically inert and chemically stable prior to photolysis. Once
irradiated, it should react rapidly with a high quantum efficiency and the photocleavage product should also be
biologically inert.
One of the main reactions used in this context is b-cleavge of benzoin esters (Section
9.29). In the examples provided in Scheme 9.88 benzoin esters are used as photoactive compounds to release
biological molecules such as adenosine monophosphate, neurotramsitters such as GABA and glutamate and
oligopeptides. The first step is to link the biological molecule of interest with benzoin (as an ester). Once this
is done the caged molecule can be photolyzed in the medium of interest to release the molecule. Release of
oligopeptides by this process can be utilized to investigate the process of protein folding.
94
Final 1.0, 4/13/2004
NH2
N
O
O O
P
O O
O
N
N
N
N
hn
O O
P
OH2 O
OH
N
O
OH
NH2
N
N
+
O
Ph
cAMP
Desyl "caged" cAMP
NH3+
O
O
hn
O
+
O
NH3
O_
+
O
GABA
Ph
Ac-Val-Gly-Glu-Arg-Gly-OH +
Ac-Val-Gly-Glu-Arg-Gly-O
Ph
hn
Ph
O
O
O
O
CO-Gly-Arg-Nle-Lys-Glu-NH
CO-Gly-Arg-Nle-Lys-Glu-NH2
Scheme 9.88
95
Final 1.0, 4/13/2004
9. 41. A comparison of carbonyl photochemistry with that of thiocarbonyls: Reactions from S2 pp*
state
While discussing the reactivity of carbonyl compounds our attention focussed essentially on the
reactivity of np* excited state. Only in aryl alkyl and diaryl ketones we were concerned to a small degree about
the reactivity of pp* state. Even in these cases we were not sure whether the reactivity is due to ‘pure’ pp*
state or due to mixing with close lying np* state. Thus it is unclear whether a ‘pure’ pp* state of a carbonyl
would undergo hydrogen abstraction, addition to alkenes etc. When one analyzes the excited state reactivity of
thiocarbonyl chromophore, a close analogue of carbonyl, it is clear that even pure pp* state can display many
of the reactions of np* state. In this section we briefly highlight the reactions of thiocarbonyls from S2 (pp*)
state to dispel the notion that pp* state can’t exhibit reactivity similar to a np* state.
Reactions from the
lowest excited np* triplet of thiocarbonyls are similar to that of carbonyls and will not be discussed. The
difference in energy between S1 and S2 in thiones is 20–40 kcal/mole making the two states ‘pure’.
Thioketones, in general, are colored compounds with electronic absorption in the region 200-700 nm
(Figure 9.17). The absorption at the longest wavelength for each of the thiones, is attributed to the spinforbidden S0 Æ T1 (np*; e~1–5) transition. The stronger band in the visible region (with small differences in
band maxima between aromatic, aliphatic and arylalkyl thiones) corresponds to the S0 Æ S1 (np*; e~100)
transition. The strongest absorption band of the aliphatic thiones in the 230-250 nm region has been attributed
to a pÆp* transition. The absorption of substituted thiobenzophenones between 300-375 nm is ascribed to
the pÆp* transition. The thiocarbonyl chromophore possesses several interesting chemical and spectroscopic
properties. Many of the characteristic features of these systems arise from the large energy separating the
S1(np*) and S2(pp*) states when compared to the same in carbonyls. One of the more unusual features is
the observation of fluorescence from the second excited singlet state (Figure 9.18). Thiones displaying
anomalous fluorescence in solution include several diaryl, aryl alkyl, dialkyl and a,b-unsaturated thiones. In
addition to the anomalous emission from S2 , thiones also react from S2 (pp* state). In this section we are
concerned with the reactivity of S2 .
96
Final 1.0, 4/13/2004
Figure 9.17
Figure 9.18
9. 42. Intramolecular hydrogen abstraction
Similar to their carbonyl counterparts thiocarbonyl compounds, have been established to undergo
hydrogen abstraction process. In carbonyl compounds, hydrogen abstraction generally occurs from the np*
state and the partially filled electrophilic n-orbital initiates this process.
In contrast, thiocarbonyls abstract
hydrogen from both the lower np* state and the upper pp* state, and the abstracted hydrogen adds to either
the C or S atom of the thiocarbonyl chromophore.
Aryl alkyl thiones containing saturated hydrocarbon alkyl chains upon excitation to the S2(pp*) state,
yield cyclopentane thiols via a d-hydrogen abstraction from the alkyl chain (Scheme 9.89).
does not occur upon irradiation to the S1(np*) band.
This reaction
Successful quenching of the reaction by singlet
quenchers and unsuccessful triplet sensitization are taken to support S2(pp*) as the reactive state.
97
Final 1.0, 4/13/2004
R
S
R
R
HS .
hu pp*
HS
.
!!
R = CH3 , Ph
R = CH3 , Ph
Scheme 9.89
Aryl alkyl thiones in which the d-carbon is replaced by an ethereal oxygen atom, photochemical
hydrogen abstraction occurs from carbons adjacent (e and/or g) to the oxygen atom (Scheme 9.90) as a result
of activation of the neighboring hydrogens by the heteroatom. e-Hydrogen abstraction leads to six membered
ring thiols, while g-hydrogen abstraction leads to cyclization (cyclobutanethiols) and cleavage (alkene)
products. Whereas the g-hydrogen abstraction can be initiated by light of short and long wavelength, ehydrogen abstraction is wavelength specific and occurs only upon excitation to the S2 state.
O
hu
SH +
pp*
S
O
O
O
+
HS
O
hu
np*
+
O
HS
Scheme 9.90
Bridged bicyclic thiones (e. g., bicycloheptanethiones and bicyclooctanethiones) on irradiation yield binsertion products. This reaction, which occurs only upon excitation to the S2 (pp*) state, is illustrated in
Scheme 9.91 using bicyclic thiones - thiofenchone and 2,2-dipropyl thiofenchone, as examples. In both these
thiones, hydrogen abstraction leading to tricyclic thiols takes place from the carbon b to the thiocarbonyl
group.
Availability of b, g, and d-hydrogens in the alkyl side chain of 2,2-dipropyl thiofenchone does not
98
Final 1.0, 4/13/2004
change the course of reaction. The participation of b-endo-hydrogen during cyclization has been confirmed by
deuterium labeling studies. No analogous reaction is known among structurally similar bicyclic ketones (recall
that fenchone, camphor etc. upon excitation undergo a-cleavage reaction).
hu
pp*
S
SH
hu
+
pp*
S
SH
SH
Scheme 9.91
Monocyclic thiones such as 2,2,5,5-tetraalkyl thiocyclopentanones and 2,2,6,6-tetraalkyl
thiocyclohexanones also react from the S2(pp*) state similar to bicyclic thiones, but the mode of hydrogen
abstraction is dependent on the alkyl side chain (Scheme 9.92).
When the alkyl groups are methyl groups,
the products of hydrogen abstraction are cyclopropyl thiols (b-insertion).
However, irradiation of thiones
with a longer alkyl chain leads to g-insertion as major and b-insertion as minor products; d-insertion pathway
is virtually absent. These reactions which can not be sensitized are believed to originate from S2.
S
HS
hu
pp*
S
HS
hu
pp*
HS
+
(11%)
(61%)
Scheme 9.92
The pp* singlet of thiocarbonyls is established to abstract hydrogens at rate ~108 s–1, a rate higher
than that reported for pp* states of carbonyls and alkenes. For an efficient hydrogen abstraction to occur the
99
Final 1.0, 4/13/2004
C—H bond must lie above or below the p-plane of the thiocarbonyl chromophore or else radiationless decay
or reaction with a solvent molecule occur. The conformation in which the molecule finds itself upon excitation
is clearly of major importance. With a short lifetime of the reactive state from which the thione undergoes
hydrogen abstraction, the relevant hydrogen atom necessarily has to be in the space pertinent to the reaction at
the time of excitation. This is presumably why the endo hydrogen successfully competes with b, g, d
hydrogens for abstraction in bicyclic thiones. In the case of arylakylthiones, the volume of space within which
the hydrogen has to be present is more easily satisfied by the d hydrogen than by the g-hydrogen. The location
of the hydrogen atoms that are abstracted by the pp* excited thiocarbonyl chromophore are thus different from
the corresponding carbonyl compounds.
9.43. Intermolecular hydrogen abstraction
Photochemical behavior of adamantanethione brings out clearly the reactivity of pp* state towards
hydrogen abstraction. Irradiation of adamantanethione in the np* band in cyclohexane gives only the 1,3dithietane dimer and no reduction products are observed. In contrast to the np* state, the pp* state of
adamantanethione is a fairly indiscriminate abstracter of hydrogen atoms. In cyclohexane, solvent insertion
products, sulfide and thiol (Scheme 9.93) along with the 1,3-dithietane dimer are formed. This reduction has
been shown to involve hydrogen abstraction and radical pairs.
The most striking result reported in this
connection is the lack of discrimination among the different types of C—H bonds. Thus primary, secondary
and tertiary hydrogens are abstracted equally efficiently by adamantanethione in its S2 state.
For example,
when 2,4-dimethylbutane is used as the donor, both the primary and tertiary hydrogens are abstracted at almost
the same rate. The indiscriminate hydrogen abstraction process is indicative of low activation energy, an early
transition state and a highly exothermic reaction.
In agreement with this, the kinetic isotope effect for the
abstraction process was determined to be close to unity. The kinetic isotope effect (kH/kD) for triplet
benzophenone hydrogen abstraction is 2.8 while that for adamantanethione in its S2 state is ~1.1. The rates of
quenching of the S2 state of thiones by hydrocarbons have been estimated to be near diffusion limited. Thus
100
Final 1.0, 4/13/2004
thiones in their S2 (pp*) states are clearly much more reactive towards C—H bonds than carbonyls in their
np* states or alkenes in their pp* states.
SH
S
hu / pp*
S
+
S
S
+
Scheme 9.93
An interesting point to note in Scheme 9.93 is that in the pp* state both carbon as well as sulfur of
thiocarbonyl chromophore abstracts hydrogen from cyclohexane. This is consistent with the Salem diagrams
for approach of C—H along the p-plane towards the C=S chromophore. We can make use of the Salem
diagram presented for the addition of carbonyl to alkene along the p-plane (Figure 9.15) to understand the
hydrogen abstarction process. As per this correlation diagram addition to carbon as well as sulfur would be
favored in the pp* state although in the np* state addition only to carbon is allowed.
9. 44. Addition to alkenes
Both diarylthiones as well as dialkylthiones add to alkenes upon excitation to S1 and S2 . Triplet np* is
the reactive state upon long wavelength excitation and excited singlet pp* upon short wavelength excitation.
Thte characteristics of addition from T1 are similar to that of carbonyls and will not be discussed.
Photochemistry of adamantanethione as a representative of the photoaddition of thiocarbonyls (S2 , pp*) to
alkenes is presented. Upon excitation to S2, adamantanethione add to both electron rich and poor alkenes to
yield thietanes. These additions are stereospecific and regioselective (Scheme 9.94). The characteristics of
additions are different from the one occurring from np* triplet state which is nonstereospecific and
regiospecific. Based on sensitization and quenching studies and the nature of products formed the reactive
state has been identified to be the S2 state. Based on quenching data the lifetime of the reactive state was
estimated to be 10-10 sec.
101
Final 1.0, 4/13/2004
S
X
S
X
S
X
+
(X = CN ; OEt )
hn
S
pp*
CN
NC
CN
CN
Scheme 9.94
From the examples presented above it is clear that pp* excited state of thiocarbonyls are as reactive as
np* excited carbonyls. Based on the behavior of thiocarbonyls it should not be a surprise if pp* excited
carbonyls undergo hydrogen abstraction and addition to alkenes.
9.45.
Other related chromophores
In this chapter we have discussed the basic primary chemical processes of excited carbonyl
chromophores: hydrogen abstraction, electron transfer, a and b-clevages and addition to unstaturated systems.
Although the discussion was restricted to ketones and aldehydes, such reactions are expected from carbonyls
present as a part of other chromophores listed in Scheme 9.95. This is illustrated with one example, ester
(Scheme 9.96).
O
O
H3C
H
H
H
H3C
O
CH3
R
O
H
CH3
O
O
R
O
O
CH3
O
N
H
CH3
O
O
O
R
R
O
R
O
O
R
R
N
H
N
H
R
Scheme 9.95
102
Final 1.0, 4/13/2004
O
OH
hu
O
O
H
CH3OH
Reduction via Hydrogen Abstraction
OH
O
hu
O
O
H
Ar2NCH3
Reduction via electron transfer
O
O
O
O
Norrish type II
O
hu
O
R
OH
hu
a-Cleavage
O
R
OH
O
RH + CO2 +
CH4
hu
O
O
b-Cleavage
Scheme 9.96
9.46. Overview
The most common reactive state of the carbonyl chromophore is the np* state. The np* state can be
visualized to be electrophilic along the n-orbital and nucleophilic along the p-face. Upon excitation the
carbonyl chromophore gives rise to several primary reactions depending on the nature of the lowest excited
state (np* or pp*). a-Cleavage and b-cleavage often result in fragmentation of the carbonyl system. The acleavage process is known as the Norrish type I reaction. In the np* excited state the carbonyl chromophore is
capable of abstracting a hydrogen atom or an electron. A consequence of this is the reduction of the carbonyl
103
Final 1.0, 4/13/2004
chromophore. When the hydrogen transfer occurs intramolecularly, specifically from the g-position, the
reaction is known as the Norrish-Yang reaction. The np* excited carbonyl chromophore may interact with a
C=C p system, either via the half occupied n-orbital or through the electron rich p* face. Since the electronic
characteristics of the two faces are different, addition to electron-rich alkenes occurs along the n face and to
electron-poor alkenes via the p-face. Addition of alkenes to excited carbonyl compounds is generally known
as the Paterno-Buchi reaction. Models based on frontier orbital interactions and Salem correlation diagrams
allow one to understand the reactivity of the carbonyl chromophore.
104
Final 1.0, 4/13/2004
References
(1)
Coenjarts, C.; Scaiano, J. C. J. Am. Chem. Soc. 2000, 122, 3635-3641.
(2)
Rajesh, C. S.; Givens, R. S.; Wirz, J. J. Am. Chem. Soc. 2000, 122, 611-618.
(3)
Bach, T.; Bergmann, H.; Harms, K. Angew. Chem. Int. Ed. Engl. 2000, 39, 2302-2304.
(4)
Bassani, D. M.; Darcos, V.; Mahony, S.; Desvergne, J.-P. J. Am. Chem. Soc. 2000, 122, 8795-8796.
(5)
Bach, T.; Bergmann, H. J. Am. Chem. Soc. 2000, 122, 11525-11526.
(6)
Ihmels, H.; Scheffer, J. R. Tetrahedron 1999, 55, 885-907.
(7)
Sun, D.; Hubig, S. M.; Kochi, J. K. J. Org. Chem. 1999, 64, 2250-2258.
(8)
Bach, T.; Bergmann, H.; Harms, K. J. Am. Chem. Soc. 1999, 121, 10650-10651.
(9)
Johnson, B. A.; Garcia-Garibay, M. A. The Spectrum 1998, 11,
(10)
Srivatsava, S.; Yourd, E.; Toscano, P. J. Am. Chem. Soc. 1998, 120, 6173-6174.
(11)
Gamarnik, A.; Johnson, B. A.; Garcia-Garibay, M. A. J. Phys. Chem. A 1998, 102, 5491-5498.
(12)
Rock, R. S.; Chan, S. I. J. Am. Chem. Soc. 1998, 120, 10766-10767.
(13)
Park, C.-H.; Givens, R. S. J. Am. Chem. soc. 1997, 119, 2453-2463.
(14)
Shi, Y.; Corrie, J. E. T.; Wan, P. J. Org. Chem. 1997, 62, 8278-8279.
(15)
Weigel, W.; Wagner, P. J. J. Am. Chem. Soc. 1996, 118, 12858-12859.
(16)
Gudmundsdottir, A. D.; Lewis, T. J.; Randall, L. H.; Scheffer, J. R.; Rettig, S. J.; Trotter, J.; Wu, C.H. J. Am. Chem. Soc. 1996, 118, 6167-6184.
(17)
Gudmundsdottir, A. D.; Lewis, T. J.; Randall, L. H.; Scheffer, J. R.; Rettig, S. J.; Trotter, J.; Wu, C.H. J. Am. Chem. Soc. 1996, 118, 6167-6184.
(18)
Garcia-Garibay, M. A.; Jenks, W. S.; Pang, L. J. Photochem. Photobiol. A : Chemistry 1996, 96, 5155.
(19)
Johnson, B. A.; Gamarnik, A.; Garcia-Garibay, M. A. J. Phys. Chem. 1996, 100, 4697-4700.
(20)
Leigh, W. J.; Lathioor, E. C.; Pierre, M. J. S. J. Am. Chem. Soc. 1996, 118, 12339-12348.
(21)
Cameron, J. F.; Willson, C. G.; Frechet, J. M. J. J. Am. Chem. Soc. 1996, 118, 12925-12937.
(22)
Gee, K. R.; Kueper, I., L. W.; Barnes, J.; Dudley, G.; Givens, R. S. J. Org. Chem. 1996, 61, 12281233.
(23)
Kresge, A. J. Chem. Soc. Rev. 1996, 275-280.
105
Final 1.0, 4/13/2004
(24)
Rock, R. S.; Chan, S. I. J. Org. Chem. 1996, 61, 1526-1529.
(25)
Griesbeck, A. G. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool
and P.-S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 550-559.
(26)
Rubin, M. B. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool and
P.-S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 430-436.
(27)
Roberts, S. M. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool
and P.-S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 408-415.
(28)
Wagner, P. J. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool and
P.-S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 449-470.
(29)
Garcia-Garibay, M. A.; Gamarnik, A.; Bise, R.; Pang, L.; Jenks, W. S. J. Am. Chem. Soc. 1995, 117,
10264-10275.
(30)
Rao, P. V.; Rao, N. B.; Ramamurthy, V. In CRC Handbook of Organic Photochemistry and
Photobiology; W. Horspool and P.-S. Song, Eds.; CRC Press: Boca Raton, 1995; pp 793-802.
(31)
Griesbeck, A. G. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool
and P.-S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 522-535.
(32)
Pirrung, M. C.; Bradley, J., -C. J. Org. Chem. 1995, 60, 1116-1117.
(33)
Carless, H. A. J. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool
and P.-S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 560-569.
(34)
Bohne, C. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool and P.S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 416-422.
(35)
Descotes, G. L. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool
and P.-S. Song, Eds.; CRC Press Boca Raton: Boca Raton, 1995; pp 501-512.
(36)
Bohne, C. In CRC Handbook of Organic Photochemistry and Photobiology; W. M. Horspool and P.S. Song, Eds.; CRC Press, Inc.,: Boca Raton, 1995; pp 423-429.
(37)
Pirrung, M. C.; Huang, C., -Y. Tet. Lett. 1995, 36, 5883-5884.
(38)
Ramamurthy, V.; Rao, N. B.; Rao, P. V. In CRC Handbook of Organic Photochemistry and
Photobiology; W. Horspool and P.-S. Song, Eds.; CRC Press: Boca Raton, 1995; pp 775-792.
(39)
Eckert, G.; Goez, M. J. Am. Chem. Soc. 1994, 116, 11999-12009.
106
Final 1.0, 4/13/2004
(40)
Lipson, M.; Noh, T.; Doubleday, C. E.; Zaleski, J. M.; Turro, N. J. J. Phys. Chem. 1994, 98, 88448850.
(41)
Wagner, P. J.; Pabon, R.; Park, B.-S.; Zand, A. R.; Ward, D. L. J. Am. Chem. Soc. 1994, 116, 589596.
(42)
Pirrung, M. C.; Shuney, S. W. J. Org. Chem. 1994, 59, 3890-3897.
(43)
Garcia-Garibay, M. A.; Gamarnik, A.; Pang, L.; Jenks, W. S. J. Am. Chem. Soc. 1994, 116, 1209512096.
(44)
Griesbeck, A. G.; Mauder, H.; Stadtmuller, S. Acc. Chem. Res. 1994, 27, 70 - 75.
(45)
Bach, T. Tetrahedron Lett. 1994, 35, 5845-5848.
(46)
Sauers, R. R.; Edberg, L. A. J. Org. Chem. 1994, 59, 7061-7066.
(47)
Bach, T.; Jodicke, K. Chem. Ber. 1993, 126, 2457-2466.
(48)
Monroe, B. M.; Weed, G. C. Chem. Rev. 1993, 93, 435-448.
(49)
Davidson, R. S. J. Photochem. Photobiol. A: Chem., 1993, 73, 81-96.
(50)
Noh, T.; Lei, X.-G.; Turro, N. J. J. Am. Chem. Soc. 1993, 115, 3105-3110.
(51)
Noh, T.; Step, E.; Turro, N. J. J. Photochem. Photobiol A 1993, 72, 133-145.
(52)
Givens, R. S.; Athey, P. S.; Matuszewski, B.; Kueper, I., L. W.; Xue, J., -y.; Fister, T. J. Am. Chem.
Soc. 1993, 115, 6001-6012.
(53)
Matsumura, M.; Ammann, J. R.; Sheridan, R. S. Tetrahedron Lett. 1992, 33, 1843-1846.
(54)
Kraus, G. A.; Wu, Y. J. Am. Chem. Soc. 1992, 114, 8705-8707.
(55)
Step, E. N.; Buchachenko, A. L.; Turro, N. J. J. Org. Chem. 1992, 57, 7018-7024.
(56)
Step, E. N.; Buchachenko, A. L.; Turro, N. J. J. ORg. Chem. 1992, 57, 7018-7024.
(57)
Wagner, P. J.; Cao, Q.; Pabon, R. J. Am. Chem. Soc. 1992, 114, 346-348.
(58)
Formosinho, S. J.; Arnaut, L. G. In Adv. Photochem.; D. Volman, G. Hammond and D. Neckers,
Eds.; John Wiley & Sons: NewYork, 1991; Vol. 16; pp 67-.
(59)
Wagner, P. J.; Subrahmanyam, D.; Park, B.-S. J. Am. Chem. Soc. 1991, 113, 709-710.
(60)
Chiang, Y.; Kresge, A. J. Science 1991, 253, 395 - 400.
(61)
Al-Soufi, W.; Eychmuller, A.; Grellmann, K. H. J. Phys. Chem. 1991, 95, 2022-2026.
(62)
Khan, N.; Morris, T. H.; Smith, E. H.; Walsh, R. J. Chem. Soc., Perkin Trans. 1 1991, 865-870.
107
Final 1.0, 4/13/2004
(63)
Devadoss, C.; Fessenden, R. W. J. Phys. Chem. 1991, 95, 7253-7260.
(64)
Gristan, N. P.; Khmelinski, I. V.; Usov, O. M. J. Am. Chem. Soc 1991, 113, 9615-9620.
(65)
Shimamori, H.; Uegaito, H.; Houdo, K. J. Phys. Chem. 1991, 95, 7664-7667.
(66)
Wagner, P.; Park, B.-S. In Organic Photochemistry; A. Padwa, Ed.; Marcel Dekker, Inc.,: New York,
1991; Vol. 11; pp 227-366.
(67)
Sakata, T.; Takahashi, S.; Terazima, M.; Azumi, T. J. Phys. Chem. 1991, 95, 8671-8676.
(68)
Fischer, H.; Baer, R.; Hany, R.; Verhoolen, I.; Walbiner, M. J. Chem. Soc. Perkin Trans. II 1990,
787-798.
(69)
Keefle, J. R.; Kresge, A. J.; Schepp, N. P. J. Am. Chem. Soc. 1990, 112, 4862-4868.
(70)
Dorigo, A. E.; McCarrick, M. A.; Loncharich, R. J.; Houk, K. N. J. Am. Chem. Soc. 1990, 112, 75087514.
(71)
Scaiano, J. C.; Wintgens, V.; Netto-Ferreira, J. C. Pure & Appl. Chem. 1990, 62, 1557-1564.
(72)
Reinsch, M.; Klessinger, M. J. Phys. Org. Chem. 1990, 3, 81-88.
(73)
Tahara, T.; Hamaguchi, H.-O.; Tasumi, M. J. Phys. Chem. 1990, 94, 170-178.
(74)
Weedon, A. C. In The Chemistry of Enols; Z. Rappoport, Ed.; John Wiley & Sons: New York, 1990;
pp 591 - 638.
(75)
Wagner, P. J.; Meador, M. A.; Park, B.-S. J. Am. Chem. Soc. 1990, 112, 5199-5211.
(76)
Sauers, R. R.; Huang, S.-Y. Tetrahedron Lett. 1990, 31, 5709-5712.
(77)
Caldwell, R. A. In Kinetics and Spectroscopy of Carbenes and Biradicals; M. Platz, Ed.; Plenum:
New York, 1990; pp 77-116.
(78)
Baldwin, J. E.; McConnaughie, A. W.; Pratt, A. J.; Shim, S. B. Tetrahedron 1990, 46, 6879-6884.
(79)
Zhou, B.; Wagner, P. J. J. Am. Chem. Soc. 1989, 111, 6796-6799.
(80)
Wagner, P. J. Acc. Chem. Res. 1989, 22, 83 - 91.
(81)
Takuwa, A.; Fujii, N.; Tagawa, H.; Iwamoto, H. Bull. Chem. Soc. Jpn. 1989, 62, 336-338.
(82)
Arbour, C.; Atkinson, G. H. Chem. Phys. Lett. 1989, 159, 520-525.
(83)
Johnston, L. J.; Scaiano, J. C. Chem. Rev. 1989, 89, 521-547.
(84)
Sun, P.-Y.; Sears, D. F. J.; Saltiel, J. J. Am. Chem. Soc. 1989, 111, 706-711.
108
Final 1.0, 4/13/2004
(85)
Turro, N. J.; Gould, I. R.; Liu, J.; Jenks, W. S.; Staab, H.; Alt, R. J. Am. Chem. Soc. 1989, 111, 63786383.
(86)
Koyanagi, M.; Futami, H.; Mukai, M.; Yamauchi, S. Chem. Phys. Lett. 1989, 154, 577-580.
(87)
Paquette, L. A.; Weber, J. C.; Kobayashi, T.; Miyahara, Y. J. Am. Chem. Soc. 1988, 110, 8591-8599.
(88)
LeBlanc, B. F.; Sheridan, R. S. J. Am. Chem. Soc. 1988, 110, 7250-7252.
(89)
Hoshino, M.; Shizuka, H. In Photoinduced Electron Transfer. Part C. Photoinduced Electron
Transfer Reactions : Organic Substrates; M. A. Fox and M. Chanon, Eds.; Elsevier: Amsterdam,
1988; pp 313-371.
(90)
Jent, F.; Paul, H.; Fischer, H. Chem. Phys. Lett. 1988, 146, 315-319.
(91)
Kesselmayer, M. A.; S., S. R. J. Am. Chem. Soc. 1987, 109, 5029-5030.
(92)
Wilson, R. M.; Hannemann, K.; Heineman, W. R.; Kirchhoff, J. R. J. Am. Chem. Soc. 1987, 109,
4743-4745.
(93)
Carless, H. A. J.; Mwesigye-Kibende, S. J. Chem. Soc., Chem. Commun. 1987, 1673-1674.
(94)
Wagner, P. J.; Lindstrom, J. J. Am. Chem. Soc. 1987, 109, 3062-3067.
(95)
Jaegermann, P.; Lendzian, F.; Rist, G.; Mobius, K. Chem. Phys. Lett. 1987, 140, 615-619.
(96)
Dorigo, E.; Houk, K. N. J. Am. Chem. Soc 1987, 109, 2195-2197.
(97)
Tahara, T.; Hamaguchi, H.-O.; Tasumi, M. J. Phys. Chem. 1987, 91, 5875-5880.
(98)
Epstein, W. W.; Garrossian, M. J. Chem. Soc., Chem. Commun. 1987, 532-533.
(99)
Roth, W. R.; Langer, R.; Bartmann, M.; Stevermann, B.; Maier, G.; Reisenauer, H. P.; Sustmann, R.;
Muller, W. Angew. Chem. Int. Ed. Engl. 1987, 26, 256-258.
(100) Reinsch, M.; Howeler, U.; Klessinger, M. Angew. Chem. Int. Ed. Engl. 1987, 26, 238-240.
(101) Gould, I. R.; Baretz, H.; Turro, N. J. J. Phys. Chem. 1987, 91, 925-929.
(102) Scheffer, J. R.; Trotter, J.; Omkaram, N.; Evans, S. V.; Ariel, S. Mol. Cryst. Liq. Cryst. 1986, 134,
169-196.
(103) Hoshi, M.; Shizuka, H. Bull. Chem. Soc. Jpn. 1986, 59, 2711-2715.
(104) Ihmels, H.; Scheffer, J. R. Tetrahedron 1986, 134, 169-196.
(105) Ando, W.; Hayakawa, H.; Tokitoh, N. Tetrahedron Lett. 1986, 27, 6357-6360.
(106) Lim, E. C. J. Phys. Chem. 1986, 90, 6770-6777.
109
Final 1.0, 4/13/2004
(107) Wagner, P. J.; Truman, R. J.; Puchalski, A. E.; Wake, R. J. Am. Chem. Soc. 1986, 108, 7727-7738.
(108) Freilich, S. C.; Peters, K. S. J. Am. Chem. Soc. 1985, 107, 3819-3822.
(109) Pirrung, M. Angew. Chem. Int. Ed. Engl. 1985, 24, 1043-1044.
(110) Shizuka, H.; Hagiwara, H.; Satoh, H.; Fukushima, M. J. Chem. Soc., Chem. Commun. 1985, 14541455.
(111) Wilson, R. M. In Organic Photochemistry; A. Padwa, Ed.; Marcel Dekker, Inc.,: New York, 1985;
Vol. 7; pp 339-466.
(112) Wagner, P. J.; Meador, M. A.; Giri, B. P.; Sciaiano, J. C. J. Am. Chem. Soc 1985, 107, 1087-1088.
(113) Ramamurthy, V. In Organic Photochemistry; A. Padwa, Ed.; Marcell Dekker: New York, 1985; Vol.
7; pp 231-338.
(114) Ferreira, J. C.-N.; Leigh, W. J.; Scaiano, J. C. J. Am. Chem. Soc. 1985, 107, 2618-2622.
(115) Carless, H. A. J.; Fekarurhobo, G. K. Tetrahedron Lett. 1984, 25, 5943-5946.
(116) Carless, H. A. J. In Synthetic Organic Photochemistry; W. M. Horspool, Ed.; Plenum Press: New
York, 1984; pp 425-487.
(117) Alt, R.; Staab, H. A.; Reisenauer, H. P.; Maier, G. Tet. Lett. 1984, 25, 633-636.
(118) Schreiber, S. L.; Satake, K. J. Am. Chem. Soc. 1984, 106, 4186-4188.
(119) Wagner, P. J.; Meador, M. A. J. Am. Chem. Soc. 1984, 106, 3684-3685.
(120) Simon, J. D.; Peters, K. S. Acc. Chem. Res. 1984, 17, 277 - 283.
(121) Shizuka, H.; Kimura, E. Can. J. Chem. 1984, 62, 2041-2046.
(122) Krebs, A.; Cholcha, W.; Muller, M.; Eicher, T.; Pielartzik, H.; Schnockel, H. Tetrahedron Lett. 1984,
25, 5027-5030.
(123) Caldwell, R. A. Pure & Appl. Chem. 1984, 56, 1167-1177.
(124) Grewal, R. S.; Burnell, D. J.; Yates, P. J. Chem. Soc., Chem. Commun. 1984, 759-760.
(125) Orban, I.; Schaffner, K.; Jeger, O. J. Am. Chem. Soc 1983 (reprinted), 85, 3033.
(126) Encina, M. V.; Lissi, E. A.; Lemp, E.; Zanocco, A.; Scaiano, J. C. J. Am. Chem. Soc. 1983, 105,
1856-1860.
(127) Lunazzi, L.; Ingold, K. U.; Scalano, J. C. J. Phys. Chem. 1983, 87, 529-530.
(128) Turro, N. J.; Gould, I. R.; Baretz, B. H. J. Phys. Chem. 1983, 87, 531-532.
110
Final 1.0, 4/13/2004
(129) Quinkert, G.; Stark, H. Angew. Chem. Int. Ed. Engl. 1983, 22, 637-740.
(130) Wagner, P. J. Acc. Chem. Res. 1983, 16, 461-467.
(131) Paquette, L. A.; Balogh, D. W. J. Am. Chem. Soc. 1982, 104, 774-783.
(132) Fessenden, R. W.; Carton, P. M.; Shimamori, H.; Scaiano, J. C. J. Phys. Chem. 1982, 86, 3803-3811.
(133) Wilson, R. M.; Wunderly, S. W.; Walsh, T. F.; Musser, A. K.; Outcalt, R.; Geiser, F.; Gee, S. K.;
Brabender, W.; Yerino, L. J.; Conrad, T. T.; Tharp, G. A. J. Am. Chem. Soc. 1982, 104, 4429-4446.
(134) Mayo, P., -d.; Nakamura, A.; Tsang, P. W. K.; Wong, S. K. J. Am. Chem. Soc. 1982, 104, 68246825.
(135) Scaiano, J. C. Tetrahedron 1982, 38, 819 - 824.
(136) Caldwell, R. A.; Majima, T.; Pac, C. J. Am. Chem. Soc. 1982, 104, 629-630.
(137) Scaiano, J. C. Acc. Chem. Res. 1982, 15, 252-258.
(138) Johnston, L. J.; Mayo, P., -d. J. Am. Chem. Soc. 1982, 104, 307-309.
(139) Rubin, M. B. Tetrahedron Letters 1982, 23, 4615-4618.
(140) Purohit, P. C.; Sonawane, H. R. Tetrahedron 1981, 37, 873-877.
(141) Chapman, O. L.; Gano, J.; West, P. R. J. Am. Chem. Soc. 1981, 103, 7033-7036.
(142) Weiss, D. S. In Organic Photochemistry; A. Padwa, Ed.; Marcel Dekker, Inc.,: New York, 1981; Vol.
5; pp 347-406.
(143) Wagner, P. J.; Stratton, T. J. Tetrahedron. 1981, 37, 3317-3322.
(144) Bigot, B.; Devaquet, A.; Turro, N. J. J. Am. Chem. Soc. 1981, 103, 6-12.
(145) Maharaj, U.; Winnik, M. A. J. Am. Chem. Soc. 1981, 103, 2328-2333.
(146) Das, P. K.; Encinas, M. V.; Scaiano, J. C. J. Am. Chem Soc. 1981, 103, 4154-4162.
(147) Jones, G. I. In Organic Photochemistry; A. Padwa, Ed.; Marcel Dekker, Inc.,: New York, 1981; Vol.
5; pp 1 - 107.
(148) Mar, A.; Winnik, M. A. Chem. Phys. Lett. 1981, 77, 73-76.
(149) Givens, R. S. In Organic Photochemistry; A. Padwa, Ed.; Marcel Dekker, Inc.,: New York, 1981;
Vol. 5; pp 227-331.
(150) Inbar, S.; Linschitz, H.; Cohen, S. G. J. Am. Chem. Soc. 1981, 103, 1048-1054.
(151) Winnik, M. A. Chem. Rev. 1981, 81, 491-524.
111
Final 1.0, 4/13/2004
(152) Turro, N. J.; Farrington, G. L. J. Am. Chem. Soc. 1980, 102, 6051-6055.
(153) Inbar, S.; Linschitz, H.; Cohen, S. G. J. Am. Chem. Soc. 1980, 102, 1419-21.
(154) Lee, E. K. C.; Lewis, R. S. In Adv. Photochem.New York, 1980; Vol. 12; pp 1 - 96.
(155) Scaiano, J. C. J. Am. Chem. Soc. 1980, 102, 7747-7753.
(156) Wagner, P. J. In Rearrangements in Ground and Excited States; P. De Mayo, Ed.; Academic press:
New York, 1980; pp 381.
(157) Turro, N. J.; Farrington, G. L. J. Am. Chem. Soc. 1980, 102, 6056-6063.
(158) Breslow, R. Acc. Chem. Res. 1980, 13, 170 - 177.
(159) Shaefer, C. G.; Peters, K. S. J. Am. Chem. Soc. 1980, 102, 7566-7567.
(160) Jost, P.; Chaquin, P.; Kossanyi, J. Tet. Lett. 1980, 21, 465-466.
(161) Encinas, M. V.; Scaiano, J. C. J. Photochem. 1979, 11, 241-247.
(162) Das, P. K.; Encinas, M. V.; Small, R. D. J.; Scaiano, J. C. J. Am. Chem. Soc. 1979, 101, 6965-6969.
(163) Maier, G.; Pfriem, S.; Schafer, U.; Matusch, R. Angew. Chem. Int. Ed. Engl. 1978, 17, 520-521.
(164) Murai, H.; Jinguji, M.; Obi, K. J. Am. Chem. Soc. 1978, 82, 38-40.
(165) Encinas, M. V.; Scaiano, J. C. J. Am. Chem. Soc. 1978, 100, 7108-7109.
(166) Weiss, D. S. Tetrahedron Lett. 1978, 12, 1039-1042.
(167) Small, R. D. J.; Scaiano, J. C. J. Am. Chem. Soc. 1978, 100, 296-298.
(168) Small, R. D. J.; Scaiano, J. C. J. Phys. Chem. 1978, 82, 2662-2664.
(169) Small, R. D. J.; Scaiano, J. C. Chem. Phys. Lett. 1978, 59, 246-247.
(170) Scaiano, J. C.; Lissi, E. A.; Encina, M. V. Reviews of Chemical Intermediates 1978, 2, 139-196.
(171) Devaquet, A.; Sevin, A.; Bigot, B. J. Am. Chem. Soc. 1978, 100, 2009-2011.
(172) Borer, A.; Kirchmayr, R.; Rist, G. Helv. Chim. Acta 1978, 61, 305-324.
(173) Berger, M.; McAlpine, E.; Steel, C. J. Am. Chem. Soc 1978, 100, 5147-5151.
(174) Denny, M.; Liu, R. S. H. J. Am. Chem. Soc. 1977, 99, 4865-4867.
(175) Carless, H. A. J.; Maitra, A. K. Tetrahedron Letters 1977, 1411-1412.
(176) Yang, N. C.; Hui, M. H.; Shold, D. M.; Turro, N. J.; Hautala, R. R.; Dawes, K.; Dalton, J. C. J. Am.
Chem. Soc. 1977, 99, 3023-3033.
(177) Small, R. D. J.; Scaiano, J. C. J. Phys. Chem. 1977, 81, 2126-2131.
112
Final 1.0, 4/13/2004
(178) Wolf, M. W.; Brown, R. E.; Singer, L. A. J. Am. Chm. Soc. 1977, 99, 526-531.
(179) Weiss, D. S.; Kochanek, P. M.; Lipka, J. J. Tetrahedron Lett. 1977, 14, 1261-1264.
(180) Weiss, D. S.; Kochanek, P. M. Tetrahedron Lett. 1977, 9, 763-766.
(181) Small, R. D. J.; Scaiano, J. C. Chem. Phys. Lett. 1977, 50, 431-434.
(182) Small, R. D.; C., S. J. J. Phys. Chem. 1977, 81, 828-832.
(183) Connors, R. E.; Walsh, P. S. Chem. Phys. Lett. 1977, 52, 436-438.
(184) Scaiano, J. C. J. Am. Chem. Soc. 1977, 99, 1494-1498.
(185) Winnik, M. A. Acc. Chem. Res. 1977, 10, 173-179.
(186) Wagner, P. J. Pure & Appl. Chem. 1977, 49, 259-270.
(187) Topp, M. R. Chem. Phys. Lett. 1976, 39, 423-426.
(188) Yates, P. J. Photochem. 1976, 5, 91-106.
(189) Wife, R. L.; Prezant, D.; Breslow, R. Tetrahedron Lett. 1976, 7, 517-520.
(190) Sammes, P. G. Tetrahedron 1976, 32, 405 - 422.
(191) de Mayo, P. Acc. Chem. Res. 1976, 9, 52-59.
(192) Lawrence, A. H.; Liao, C. C.; de Mayo, P.; Ramamurthy, V. J. Am. Chem. Soc. 1976, 98, 3572-3579.
(193) Lawrence, A. H.; Liao, C. C.; de Mayo, P.; Ramamurthy, V. J. Am. Chem. Soc. 1976, 98, 2219-2226.
(194) Turro, N. J.; Farneth, W. E.; Devaquet, A. J. Am. Chem. Soc. 1976, 98, 7425-7427.
(195) Couture, A.; Ho, K.; Hoshino, M.; de Mayo, P.; Suau, R.; Ware, W. R. J. Am. Chem. Soc. 1976, 98,
6218-6225.
(196) Wagner, P. J. In Topics in Current Chemistry; Springer-Verlag: 1976; Vol. 66; pp 1 - 52.
(197) Wagner, P. J.; Chen, C.-P. J. Am. Chem. Soc. 1976, 98, 239-241.
(198) Salem, L. Science 1976, 191, 822-830.
(199) Grimbert, D.; Salem, L. Chem. Phys. Lett. 1976, 43, 435-439.
(200) Blank, B.; Henne, A.; Laroff, G. P.; Fischer, H. Pure & Appl. Chem. 1975, 41, 475 - 493.
(201) Moule, D. C.; Walsh, A. D. Chem. Rev. 1975, 75, 67-84.
(202) Devaquet, A. Pure & Appl. Chem. 1975, 41, 455-473.
(203) Moniz, W. B.; Poranski, C. F. J.; Sojka, S. A. J. Org. Chem. 1975, 40, 2946-2949.
(204) Lewis, F. D.; Hoyle, C. H.; Magyar, J. G. J. Org. Chem. 1975, 40, 488-492.
113
Final 1.0, 4/13/2004
(205) Yates, P.; Loutfy, R. O. Acc. Chem. Res. 1975, 8, 209-216.
(206) Dauben, W. G.; Salem, L.; Turro, N. J. Acc. Chem. Res. 1975, 8, 41-54.
(207) Lewis, F. D.; Lauterbach, R. T.; Heine, H.-G.; Hartmann, W.; Rudolph, H. J. Am. Chem. Soc. 1975,
97, 1519-1525.
(208) Schore, N. E.; Turro, N. J. J. Am. Chem. Soc. 1975, 97, 2482-2488.
(209) Yates, P.; Tam, J. C. L. J. Chem. Soc., Chem. Commun. 1975, 737-738.
(210) Hamity, M.; Scaiano, J. C. J. Photochem. 1975, 4, 229-232.
(211) Salem, L. Isr. J. Chem. 1975, 14, 89-104.
(212) Salem, L.; Leforestier, C.; Segal, G.; Wetmore, R. J. Am. Chem. Soc. 1975, 97, 479-487.
(213) Givens, R. S.; Strekowski, L. J. Am. Chem. Soc. 1975, 97, 5867-5873.
(214) Charney, D. R.; Dalton, J. C.; Hautala, R. R.; Snyder, J. J.; Turro, N. J. J. Am. Chem. Soc. 1974, 96,
1407-1410.
(215) Blank, B.; Henne, A.; Fischer, H. Helv. Chim. Acta 1974, 57, 920-936.
(216) Morton, D. R.; Turro, N. J. In Adv. Photochem.; J. N. J. Pitts, G. S. Hammond and K. Gollnick,
Eds.; John Wiley & Sons: New York, 1974; Vol. 9; pp 197-309.
(217) Morris, J. M.; Williams, D. F. Chem. Phys. Lett. 1974, 25, 312-314.
(218) Bichan, D.; Winnik, M. Tetrahedron Lett. 1974, 44, 3857-3860.
(219) Carless, H. A. J. J. Chem. Soc., Perkin Trans. II 1974, 834-842.
(220) Lewis, F. D.; Johnson, R. W.; Kory, D. R. J. Am. Chem. Soc. 1974, 96, 6100-6107.
(221) Davidson, R. S. In Molecular Association; R. Foster, Ed.; Academic Press: New York, 1974; Vol. 1;
pp 215-334.
(222) Stohrer, D. W.-D.; Jacobs, P.; Kaiser, K. H.; Wiech, G.; Quinkert, G. In Topics in Current
Chemistry1974; Vol. 46; pp 181 - 236.
(223) Lewis, F. D.; Johnson, R. W.; Johnson, D. E. J. Am. Chem. Soc. 1974, 96, 6090-6099.
(224) Shimizu, N.; Ishikawa, M.; Ishikura, K.; Nishida, S. J. Am. Chem. Soc. 1974, 96, 6456-6462.
(225) Schaffner , K.; Jeger, O. Tetrahedron 1974, 30, 1891-1902.
(226) Heine, H.-G.; Hartmann, W.; Kory, D. R.; Magyar, J. G.; Hoyle, C. E.; McVey, J. K.; Lewis, F. D.
J. Org. Chem. 1974, 39, 691-698.
114
Final 1.0, 4/13/2004
(227) Scaiano, J. C. J. Photochem. 1974, 2, 81 - 118.
(228) Salem, L. J. Am. Chem. Soc. 1974, 96, 3486-3501.
(229) Rayner, D. M.; Wyatt, P. A. H. J. Chem. Soc., Faraday Trans. 2 1974, 70, 945-954.
(230) Quinkert, G.; Jacobs, P. Chem. Ber. 1974, 107, 2473-2490.
(231) Quinkert, G.; Jacobs, P. Chem. Ber. 1974, 107, 2473-2490.
(232) Quinkert, G.; Jacobs, P.; Stohrer, W.-D. Angew. Chem. Internat. Edit. 1974, 13, 197-198.
(233) Quinkert, G.; Kaiser, K. H.; Stohrer, W.-D. Angew. Chem. Internat. Edit. 1974, 13, 198-199.
(234) Porter, G.; Dogra, S. K.; Loutfy, R. O.; Sugamori, S. E.; Yip, R. W. J. Chem. Soc., Faraday Trans. 1
1973, 69, 1462-1474.
(235) Boeckman, R. K. J. J. Am. Chem. Soc. 1973, 95, 6869-6870.
(236) DeBoer, C. D.; Herkstroeter, W. G.; Marchetti, A. P.; Schultz, A. G.; Schlessinger, R. H. J. Am.
Chem. Soc. 1973, 95, 3963-3968.
(237) Chapman, O. L.; Weiss, D. S. In Organic Photochemistry; O. L. Chapman, Ed.; Marcel Dekker, Inc.,:
New York, 1973; Vol. 3; pp 198 - 277.
(238) Friedrich, L. E.; Bower, J. D. J. Am. Chem. Soc. 1973, 95, 6869-6870.
(239) Paul, H.; Fischer, H. Helv. Chim. Acta 1973, 56, 1575-1594.
(240) Pappas, S. P.; Chattopadhyay, A. J. Am. Chem. Soc. 1973, 95, 6484-6485.
(241) Morton, D. R.; Turro, N. J. J. Am. Chem. Soc. 1973, 95, 3947-3957.
(242) Lewis, F. D.; Magyar, J. G. J. Am. Chem. Soc. 1973, 95, 5973-5976.
(243) Carless, H. A. J. Tetrahedron Lett. 1973, 34, 3173-3174.
(244) Laroff, G. P.; Fischer, H. Helv. Chim. Acta 1973, 56, 2011-2020.
(245) Wagner, P. J.; Leavitt, R. A. J. Am. Chem. Soc. 1973, 95, 3669-3677.
(246) Caldwell, R. A.; Sovocool, G. W.; Gajewski, R. P. J. Am. Chem. Soc. 1973, 95, 2549-2557.
(247) Dalton, J. C.; Tremont, S. J. Tetrahedron Lett. 1973, 41, 4025-4028.
(248) Breslow, R.; Baldwin, S.; Flechtner, T.; Kalicky, P.; Liu, S.; Washburn, W. J. Am. Chem. Soc. 1973,
95, 3251-3262.
(249) Cohen, S. G.; Parola, A.; Parsons, G. H. J. Chem. Rev. 1973, 73, 141-161.
(250) Sheehan, J. C.; Umezawa, K. J. Org. Chem. 1973, 38, 3771-3774.
115
Final 1.0, 4/13/2004
(251) Wagner, P. J.; Kemppainen, A. E.; Schott, H. N. J. Am. Chem. Soc. 1973, 95, 5604-5614.
(252) Salem, L. Pure & Appl. Chem. 1973, 33, 317-328.
(253) Closs, G. L.; Doubleday , C. E. J. Am. Chem. Soc. 1973, 95, 2735-2736.
(254) Chen, H. E. C.; Groen, A.; Cocivera, M. Can. J. Chem. 1973, 51, 3032-3038.
(255) Previtali, C. M.; Scaiano, J. C. J. C. S. Perkin II 1972, 1672-1676.
(256) Friedrich, L. E.; Schuster, G. B. J. Am. Chem. Soc. 1972, 94, 1193-1199.
(257) Casey, C. P.; Boggs, R. A. J. Am. Chem. Soc 1972, 94, 6457-6463.
(258) Muller, K.; Closs, G. L. J. Am. Chem. Soc. 1972, 94, 1002-1004.
(259) McDaniel, D. M.; Turro, N. J. Tetrahedron Lett. 1972, 30, 3035-3038.
(260) Yip, R. W.; Loutfy, R. O.; Chow, Y. L.; Magdzinski, L. K. Can. J. Chem. 1972, 50, 3426-3431.
(261) Lewis, F. D.; Johnson, R. W. J. Am. Chem. Soc. 1972, 94, 8914-8915.
(262) Lewis, F. D.; Johnson, R. W.; Ruden, R. A. J. Am. Chem. Soc. 1972, 94, 4292-4297.
(263) Lewis, F. D.; Hilliard, T. A. J. Am. Chem. Soc. 1972, 94, 3852-3858.
(264) Lewis, F. F.; Magyar, J. G. J. Org. Chem. 1972, 37, 2102-2107.
(265) Appleton, T. G.; Chisholm, M. H.; Clark, H. C. J. Am. Chem. Soc. 1972, 94, 8914-8915.
(266) Ledwith, A.; Russell, P. J.; Sutcliffe, L. H. J. Chem. Soc., Perkin II 1972, 1925-1928.
(267) Wagner, P. J.; Kelso, P. A.; Kemppainen, A. E.; Zepp, R. G. J. Am. Chem. Soc. 1972, 94, 75007506.
(268) Wagner, P. J.; Kemppainen, A. E. K. J. Am. Chem. Soc 1972, 94, 7495-7499.
(269) Wagner, P. J.; McGrath, J. M. J. Am. Chem. Soc. 1972, 94, 3849-3851.
(270) Wagner, P. J.; Kelso, P. A.; Zepp, R. G. J. Am. Chem. Soc. 1972, 94, 7480-7488.
(271) Krapcho, A. P.; Waller, F. J. J. Org. Chem. 1972, 37, 1079-1083.
(272) Turro, N. J.; Lee, C. G. Mol. Photochem. 1972, 4, 427-435.
(273) Barltrop, J. A.; Carless, H. A. J. J. Am. Chem. Soc. 1972, 94, 1951-1959.
(274) Coyle, J. D.; Carless, H. A. J. Chem. Soc. Rev. 1972, 465-480.
(275) Cookson, R. C.; Rogers, N. R. J. Chem. Soc., Chem. Commun. 1972, 809-810.
(276) Breslow, R. Chem. Soc. Rev. 1972, 1, 553-580.
116
Final 1.0, 4/13/2004
(277) Turro, N. J.; Dalton, C.; Dawes, K.; Farrington, G.; Hautala, R.; Morton, D.; Niemczyx, M.; Schore,
N. Acc. Chem. Res. 1972, 5, 92 - 101.
(278) Guttenplan, J. B.; Cohen, S. G. J. Am. Chem. Soc. 1972, 94, 4040-4042.
(279) Guttenplan, J. B.; Cohen, S. G. Tetrahedron Lett. 1972, 22, 2163-2166.
(280) Salem, L.; Rowland, C. Angew. Chem. Internat. Edit. 1972, 11, 92-111.
(281) Closs, G. L.; Doubleday, C. E. J. Am. Chem. Soc. 1972, 94, 9248-9249.
(282) Wagner, P. J.; Kelso, P. A.; Kemppainen, A. E.; McGrath, J. M.; Schott, H. N.; Zepp, R. G. J. Am.
Chem. Soc. 1972, 94, 7506-7512.
(283) Pownall, H. J.; Huber, J. R. J. Am. Chem. Soc. 1971, 93, 6429-6436.
(284) Padwa, A. Acc. Chem. Res. 1971, 4, 48-57.
(285) Majeti, S. Tet. Lett. 1971, 27, 2523-2526.
(286) Yang, N. C.; Chen, R. H.-K. J. Am. Chem. Soc. 1971, 93, 530-532.
(287) Den Hollander, J. A.; Kaptein, R.; Brand, P. A. T. M. Chem. Phys. Lett. 1971, 10, 430-435.
(288) Weiner, S. A. J. Am. Chem. Soc. 1971, 93, 425-429.
(289) Dawes, K.; Dalton, J. C.; Turro, N. J. Mol. Photochem. 1971, 3, 71-78.
(290) Lange, G. L.; Bosch, M. Tetrahedron Lett. 1971, 4, 315-316.
(291) Kuntzel, H.; H., W.; Schaffner, K. Helv. Chim. Acta 1971, 54, 868-883.
(292) Wagner, P. J. Acc. Chem. Res. 1971, 4, 168-177.
(293) Buettner, A. V.; Dedinas, J. J. Phys. Chem. 1971, 75, 187-191.
(294) Turro, N. J. Pure & Appl. Chem. 1971, 27, 679-705.
(295) Bryce-Smith, D.; Cox, G. B.; Gilbert, A. J. Chem. Soc., Chem. Commun. 1971, 914-915.
(296) Stephenson, L. M.; Cavigli, P. R.; Parlett, J. L. J. Am. Chem. Soc. 1971, 93, 1984-1988.
(297) Sheehan, J. C.; wilson, R. M.; Oxford, A. W. J. Am. Chem. Soc. 1971, 93, 7222-7228.
(298) Schulte-Elte, K. H.; Willhalm, B.; Thomas, A. F.; Stoll, M.; Ohloff, G. Helv. Chim. Acta 1971, 54,
1759-1767.
(299) Breslow, R.; Scholl, P. C. J. Am. Chem. Soc. 1971, 93, 2331-2333.
(300) Breslow, R.; Kalicky, P. J. Am. Chem. Soc. 1971, 93, 3540-3541.
117
Final 1.0, 4/13/2004
(301) Quinkert, G.; Tabata, T.; Hickmann, E. A. J.; Dobrat, W. Angew. Chem. Internat. Edit. 1971, 10,
199-200.
(302) Yang, N. C.; Eisenhardt, W. J. Am. Chem. Soc. 1971, 93, 1277-1279.
(303) Gagosian, R. B.; C., D. J.; Turro, N. J. J. Am. Chem. Soc. 1970, 92, 4752-4754.
(304) Case, W. A.; Kearns, D. R. J. Chem. Phys. 1970, 52, 2175-2191.
(305) Engel, P. S. J. Am. Chem. Soc. 1970, 92, 6074-6076.
(306) Morton, D. R.; Lee-Ruff, E.; Southam, R. M.; Turro, N. J. J. Am. Chem. Soc. 1970, 92, 4349-4357.
(307) Mori, T.; Yang, K. H.; Kimoto, K.; Nozaki, H. Tetrahedron Lett. 1970, 28, 2419-2420.
(308) Maycock, A. L.; Berchtold, G. A. J. Org. Chem. 1970, 35, 2532-2538.
(309) Zimmerman, H. E.; Hixson, S. S.; McBride, E. F. J. Am. Chem. Soc. 1970, 92, 2000-2007.
(310) Zimmerman, H. E.; Moore, C. M. J. Am. Chem. Soc. 1970, 92, 2023-2027.
(311) Dowd, P. J. Am. Chem. Soc. 1970, 92, 1066-1068.
(312) Zimmerman, H. E.; Flechtner, T. W. J. Am. Chem. Soc. 1970, 92, 6931-6934.
(313) Yang, N. C.; Feit, E. D.; Hui, M. H.; Turro, N. J.; Dalton, J. C. J. Am. Chem. Soc. 1970, 92, 69746976.
(314) Lewis, F. D.; Turro, N. J. J. Am. Chem. Soc. 1970, 92, 311-320.
(315) Lewis, F. D. Tetraherdon Letters 1970, 1373-1376.
(316) Lewis, F. D.; Turro, N. J. J. Am. Chem. Soc. 1970, 92, 311-320.
(317) Wagner, P. J.; Kemppanien, A. E.; Schott, H. N. J. Am. Chem. Soc 1970, 92, 5280-5281.
(318) Wagner, P. J.; May, M. J.; Haug, A.; Graber, D. R. J. Am. Chem. Soc. 1970, 92, 5269-5270.
(319) Turro, N. J.; Lee, T. J. Mol. Photochem. 1970, 2, 185-190.
(320) Dalton, J. C.; Pond, D. M.; Weiss, D. S.; Lewis, F. D.; Turro, N. J. J. Am. Chem. Soc. 1970, 92,
2564-2566.
(321) Turro, N. J.; McDaniel, D. M. J. Am. Chem. Soc. 1970, 92, 5727-5729.
(322) Turro, N. J.; Wriede, P. A. J. Am. Chem. Soc. 1970, 92, 320-329.
(323) Dalton, J. C.; Turro, N. J. Annual Review of Physical Chemistry 1970, 21, 499-560.
(324) Dalton, J. C.; Wriede, P. A.; Turro, N. J. J. Am. Chem. Soc. 1970, 92, 1318-1326.
(325) Cohen, S. G.; Litt, A. D. Tetrahedron Lett. 1970, 11, 837-840.
118
Final 1.0, 4/13/2004
(326) Breslow, R.; Baldwin, S. W. J. Am. Chem. Soc. 1970, 92, 732-734.
(327) Cocivera, M.; Trozzolo, A. M. J. Am. Chem. Soc. 1970, 92, 1772-1774.
(328) Robbins, W. K.; Eastman, R. H. J. Am. Chem. Soc. 1970, 92, 6077-6079.
(329) Robbins, W. K.; Eastman, R. H. J. Am. Chem. Soc. 1970, 92, 6076-6077.
(330) Closs, G. L.; Paulson, D. R. J. Am. Chem. Soc. 1970, 92, 7229-7231.
(331) Turro, N. J.; McDaniel, D. M. J. Am. Chem. Soc. 1970, 92, 5727-5729.
(332) Padwa, A.; Alexander, E.; Niemcyzk, M. J. Am. Chem.Soc 1969, 91, 456-460.
(333) Yang, N. C.; Dusenbery, L. Mol. Photochem. 1969, 1, 159-171.
(334) Yang, N. C.; Elliott, S. P.; Kim, B. J. Am. Chem. Soc. 1969, 91, 7551-7553.
(335) Davis, G. A.; Carapellucci, P. A.; Szoc, K.; Gresser, J. D. J. Am. Chem. Soc. 1969, 91, 2264-2272.
(336) Laird, T.; Williams, H. J. Chem. Soc., Chem. Commun. 1969, 561-562.
(337) Davidson, R. S.; Lambeth, P. F.; Younis, F. A.; Wilson, R. J. Chem. Soc. (C). 1969, 2203-2207.
(338) Turro, N. J. Acc. Chem. Res. 1969, 2, 25-32.
(339) Barltrop, J. A.; Coyle, J. D. J. Chem. Soc., Chem. Commun. 1969, 19, 1081-1082.
(340) Cohen, G. C.; Green, B. J. Am. Chem. Soc. 1969, 91, 6824-6829.
(341) Schenck, G. O.; Koltzenburg, G.; Roselius, E. Z. Naturforschung 1969, 24 (b), 222-224.
(342) Breslow, R.; Winnik, M. A. J. Am. Chem. Soc. 1969, 91, 3083-3084.
(343) Yang, N. C.; Elliott, S. P. J. Am. Chem. Soc. 1969, 91, 7550-7552.
(344) Clark, W. D. K.; Litt, A. D.; Steel, C. J. Am. Chem. Soc. 1969, 91, 5413-5415.
(345) Pitts, J. N.; Burley, J., D. R. J. Am. Chem. Soc 1968, 90, 5900-5902.
(346) El-Sayed, M. A. Acc. Chem. Res. 1968, 1, 8-16.
(347) Zimmerman, H. E.; Hancock, K. G.; Licke, G. C. J. Am. Chem. Soc. 1968, 90, 4892-4901.
(348) Yates, P. Pure & Appl. Chem. 1968, 16, 93-113.
(349) Yang, N. C.; Feit, E. D. J. Am. Chem. Soc. 1968, 90, 504-506.
(350) Yang, N. C.; Dusenbury, R. L. J. Am. Chem. Soc. 1968, 90, 5899-5900.
(351) Agosta, W. C.; Herron, D. K. J. Am. Chem. Soc. 1968, 90, 7025-7030.
(352) Weinshenker, N. M.; Greene, F. D. J. Am. Chem. Soc. 1968, 90, 506.
(353) Davidson, R. S.; Lambeth, P. F. J. Chem. Soc., Chem. Commun. 1968, 511-512.
119
Final 1.0, 4/13/2004
(354) Wagner, P. J.; Kemppanien, A. E. J. Am. Chem. Soc 1968, 90, 5898-5899.
(355) Turro, N. J.; Weiss, D. S. J. Am. Chem. Soc. 1968, 90, 2185-2186.
(356) Iwasaki, S.; Schaffner, K. Helv. Chim. Acta 1968, 51, 557-562.
(357) Collier, J. R.; Hill, J. Chem. Comm. 1968, 700-702.
(358) Hochstrasser, R. M.; Marzzacco, C. J. Chem. Phys. 1968, 49, 971-984.
(359) Arnold, D. R. In Adv. Photochem.; W. A. Noyes, G. S. Hammond and J. N. Pitts, Eds.; John Wiley
& Sons: New York, 1968; Vol. 6; pp 301-423.
(360) Barltrop, J. A.; Coyle, J. D. Tetrahedron Lett. 1968, 28, 3235-3238.
(361) Cohen, S. G.; Chao, H. M. J. Am. Chem. Soc. 1968, 90, 165-173.
(362) Griffin, R. N. Photochem. Photobiol. 1968, 7, 159-173.
(363) Barltrop, J. A.; Coyle, J. D. J. Am. Chem. Soc. 1968, 90, 6584-6588.
(364) Rauh, R. D.; Leermakers, P. A. J. Am. Chem. Soc. 1968, 90, 2246-2249.
(365) Chapman, O. L.; Lenz, G. In Organic Photochemistry; O. L. Chapman, Ed.; Marcel Dekker, Inc.,:
New York, 1967; Vol. 1; pp 283 - 318.
(366) Padwa, A. In Organic Photochemistry; O. L. Chapman, Ed.; Marcel Dekker , Inc.,: New York, 1967;
Vol. 1; pp 91-124.
(367) McIntosh, C. L.; Mayo, P., -d.; Yip, R. W. Tet. Lett. 1967, 1, 37-42.
(368) Yang, N. C.; Loeschen, R.; Mitchell, D. J. Am. Chem. Soc. 1967, 89, 5465-5466.
(369) Yang, N. C.; McClure, D. S.; Murov, S. L.; Houser, J. J.; Dusenbury, R. J. Am. Chem. Soc. 1967, 89,
5466-5468.
(370) Lamola, A. A. J. Chem. Phys. 1967, 47, 4810-4816.
(371) Wagner, P. J. Tetrahedron Lett. 1967, 18, 1753-1756.
(372) Hess, L. D.; Jacobson, J. L.; Schaffner, K.; Pitts, J. N., Jr. J. Am. Chem. Soc. 1967, 89, 3684-3688.
(373) Schaffner, K. Pure & Appl. Chem. 1967, 16, 75-85.
(374) Porter, G.; Suppan, P. Trans. Farad. Soc. 1966, 62, 3375-3383.
(375) Yates, P.; Kilmurry, L. J. Am. Chem. Soc. 1966, 88, 1563-1564.
(376) Wehrli, H.; Lehmann, C.; Keller, P.; Bonet, J. J.; Schaffner, K.; Jeger, O. Helv. Chim. Acta 1966, 49,
2218-2256.
120
Final 1.0, 4/13/2004
(377) Wagner, P. J.; Hammond, G. S. J. Am. Chem. Soc. 1966, 88, 1245-1251.
(378) Kearns, D. R.; Case, W. A. J. Am. Chem. Soc. 1966, 88, 5087-5097.
(379) Hostettler, H. U. Helv. Chim. Acta 1966, 49, 2417-2426.
(380) Hlavka, J. J.; Bitha, P. Tet. Lett. 1966, 32, 3843-3846.
(381) Cohen, S. G.; Aktipis, S. J. Am. Chem. Soc. 1966, 88, 3587-3594.
(382) Yang, N. C.; Nussim, M.; Coulson, D. R. Tetrahedron Lett. 1965, 20, 1525-1528.
(383) Walling, C.; Gibian, M. J. J. Am. Chem. Soc. 1965, 87, 3361-3364.
(384) Beereboom, J. J.; Wittenau, M. S. V. J. Org. Chem. 1965, 30, 1231-1234.
(385) Turro, N. J.; Leermakers, P. A.; Wilson, H. R.; Neckers, D. C.; Byers, G. W.; Vesley, G. F. J. Am.
Chem. Soc. 1965, 87, 2613-2619.
(386) Godfrey, T. S.; Porter, G.; Suppan, P. Discussions Faraday Soc. 1965, 39, 194-199.
(387) Porter, G.; Suppan, P. Pure & Appl. Chem. 1964, 9, 499-505.
(388) Padwa, A. Tetrahedron Lett. 1964, 46, 3465-3469.
(389) Zimmerman, H. E. J. Am. Chem. Soc. 1964, 947-948.
(390) Yang, N. C. Pure & Appl. Chem. 1964, 9, 591-596.
(391) Yang, N. C.; Nussim, M.; Jorgenson, M. J.; Murov, S. Tetrahedron Lett. 1964, 48, 3657-3664.
(392) Jeger, O.; Schaffner, K.; Wehrli, H. Pure & Appl. Chem. 1964, 9, 555-565.
(393) Sheehan, J. C.; Wilson, R. M. J. Am. Chem .Soc. 1964, 86, 5277-5281.
(394) Quinkert, G. Pure & Appl. Chem. 1964, 9, 607-621.
(395) Arnold, D. R.; Hinman, R. L.; Glick, A. H. Tetrahedron Lett. 1964, 22, 1425-1430.
(396) Chapman, O. L. In Adv. Photochem.; W. A. J. Noyes, G. S. Hammond and J. N. J. Pitts, Eds.; John
Wiley & Sons: New York, 1963; Vol. 1; pp 323 - 413.
(397) Orban, I.; Schaffner, K.; Jeger, O. J. Am. Chem. Soc. 1963, 85, 3033-3035.
(398) Ferguson, H. G.; De Mayo, P.; Pattison, F. L. M.; Tabata, T. Can. J. Chem. 1963, 41, 2099-2100.
(399) El-Sayed, M. A. J. Chem. Phys. 1963, 38, 2834-2838.
(400) Yang, N. C.; Morduchowitz, A.; Yang, D.-D. H. J. Am. Chem. Soc. 1963, 85, 1017.
(401) Bell, J. A.; Linschitz, H. J. Am. Chem. Soc. 1963, 85, 528-532.
(402) Beckett, A.; Porter, G. Trans. Farad. Soc. 1963, 59, 2038-2050.
121
Final 1.0, 4/13/2004
(403) Johnson, C. K.; Dominy, B.; Reusch, W. J. Am. Chem. Soc. 1963, 85, 3894-3896.
(404) Srinivasan, R. In Adv. Photochem.; W. A. J. Noyes, G. S. Hammond and J. N. J. Pitts, Eds.; John
Wiley & sons: New York, 1963; Vol. 1; pp 83 - 112.
(405) Hlavka, J. J.; Krazinski, H. M. J. Org. Chem. 1963, 28, 1422-1423.
(406) Quinkert, G.; Opitz, K.; Wiersdorff, W. W.; Weinlich, J. Tetrahedron Lett. 1963, 27, 1863-1868.
(407) Pitts, J. N. J.; Johnson, H. W.; Kuwana, T. J. Phys. Chem. 1962, 66, 2456-2461.
(408) Moore, W. M.; Ketchum, M. J. Am. Chem. Soc. 1962, 84, 1368-1371.
(409) Hammomd, G. S.; Leermakers, P. A. J. Am. Chem. Soc. 1962, 84, 207-211.
(410) Cohen, S. G.; Orman, S.; Laufer, D. A. J. Am. Chem. Soc. 1962, 84, 3905-3912.
(411) Anderson, J. C.; Reese, C. B. Tet. Lett. 1962, 1, 1-4.
(412) Porter, G.; Wilkinson, F. Trans. Farad. Soc. 1961, 57, 1686-1692.
(413) Moore, W. M.; Hammond, G. S.; Foss, R. P. J. Am. Chem. Soc. 1961, 83, 2789-2794.
(414) Hammond, G. S.; Baker, W. P.; Moore, W. M. J. Am. Chem. Soc. 1961, 83, 2795-2799.
(415) Backstrom, H. L. J.; Sandros, K. Acta Chem. Scand. 1960, 14, 48-62.
(416) Ito, M.; Inuzuka, K.; Imanishi, S. J. Am. Chem. Soc 1960, 82, 1317.
(417) Ito, M.; Inuzuka, K.; Imanishi, S. J. Am. Chem. Soc. 1960, 82, 1317-1322.
(418) Pitts, J. N. J.; Letsinger, R. L.; Taylor, R. P.; Patterson, J. M.; Recktenwald, G.; Martin, R. B. J. Am.
Chem. Soc. 1959, 81, 1068-1077.
(419) Yang, N. C.; Yang, D.-D. H. J. Am. Chem. Soc. 1958, 80, 2913-2914.
(420) Schonberg, A.; Fateen, A. K.; Omran, S. M. A. R. J. Am. Chem. Soc. 1956, 78, 1224-1225.
(421) Strachan, A. N.; Blacet, F. E. J. Am. Chem. Soc. 1955, 77, 5254-5257.
(422) Buchi, G.; Inman, C. G.; Lipinsky, E. S. J. Am. Chem. Soc. 1954, 76, 4327-4331.
(423) Schonberg, A.; Mustafa, A. Chem. Rev. 1947, 40, 181-200.
(424) Bergmann, F.; Hirshberg, Y. J. Am. Chem. Soc. 1943, 65, 1429-1430.
(425) Weizmann, C.; Bergmann, E.; Hirshberg, Y. J. Am. Chem. Soc. 1938, 60, 1530-1533.
122