Download Organic Chemistry

Organic
Chemistry
William H. Brown
Christopher S. Foote
Brent L. Iverson
6-1
Reactions
of Alkenes
Chapter 6
6-2
Characteristic Reactions
Descriptive Name(s )
React ion
C C
+
HCl
( HX)
C C
+
H2 O
C C
+
Br2
( X2 )
C C
+
Br2
( X2 )
H
C C
Cl (X)
H
C C
OH
(X) Br
C C
Br (X)
H2 O
HO
C C
Br (X)
Hydrochlorination
(hydrohalogenation)
Hydration
Bromination
(halogenation)
Bromo(halo)hydrin
formation
6-3
Characteristic Reactions
C C
+ Hg(OAc) 2
C C
+
BH3
C C
+
OsO4
C C
+
H2
H2 O
HgOAc
Oxymercuration
C C
HO
C C
H BH2
Hydroboration
C C
HO OH
Diol formation
(oxidation)
C C
H H
Hydrogenation
(reduction)
6-4
Reaction Mechanisms
A
reaction mechanism describes how a reaction
occurs
• which bonds are broken and which new ones are
formed
• the order and relative rates of the various bondbreaking and bond-forming steps
• if in solution, the role of the solvent
• if there is a catalyst, the role of a catalyst
• the position of all atoms and energy of the entire
system during the reaction
6-5
Gibbs Free Energy
free energy change, DG0: a thermodynamic
function relating enthalpy, entropy, and
temperature
DG0 = DH0 –TDS0
 Gibbs
• exergonic reaction: a reaction in which the Gibbs free
energy of the products is lower than that of the
reactants; the position of equilibrium for an exergonic
reaction favors products
• endergonic reaction: a reaction in which the Gibbs free
energy of the products is higher than that of the
reactants; the position of equilibrium for an
endergonic reaction favors starting materials
6-6
Gibbs Free Energy
• a change in Gibbs free energy is directly related to
chemical equilibrium
0
DG = -RT ln Keq
• summary of the relationships between DG0, DH0, DS0,
and the position of chemical equilibrium
DS0 < 0
DH 0 > 0
DH 0 < 0
DG 0 > 0; the
position of equilibrium
favors reactants
At lower temperatures
whenTDS0 < DH0 and
DG 0 < 0, the position of
equilibrium favors
products
DS0 > 0
At higher temperatures
when TDS0 > DH0 and
DG 0 < 0, the position of
equilibrium favors
products
DG 0 < 0; the
position of equilibrium
favors products
6-7
Energy Diagrams
change, DH0: the difference in total
bond energy between reactants and products
 Enthalpy
• a measure of bond making (exothermic) and bond
breaking (endothermic)
of reaction, DH0: the difference in enthalpy
between reactants and products
 Heat
• exothermic reaction: a reaction in which the enthalpy
of the products is lower than that of the reactants; a
reaction in which heat is released
• endothermic reaction: a reaction in which the enthalpy
of the products is higher than that of the reactants; a
reaction in which heat is absorbed
6-8
Energy Diagrams
diagram: a graph
showing the changes in
energy that occur during a
chemical reaction
 Reaction coordinate: a
measure in the change in
positions of atoms during
a reaction
Energy
 Energy
Reaction
coordinate
6-9
Activation Energy
 Transition
state:
• an unstable species of maximum energy formed
during the course of a reaction
• a maximum on an energy diagram
Energy, DG‡: the difference in Gibbs
free energy between reactants and a transition
state
 Activation
• if DG‡ is large, few collisions occur with sufficient
energy to reach the transition state; reaction is slow
• if DG‡ is small, many collisions occur with sufficient
energy to reach the transition state; reaction is fast
6-10
Energy Diagram
• a one-step reaction with no intermediate
6-11
Energy Diagram
A
two-step reaction with one intermediate
6-12
Developing a Reaction Mechanism

How it is done
• design experiments to reveal details of a particular chemical
reaction
• propose a set or sets of steps that might account for the overall
transformation
• a mechanism becomes established when it is shown to be
consistent with every test that can be devised
• this does mean that the mechanism is correct, only that it is the
best explanation we are able to devise
6-13
Why Mechanisms?
• they are the framework within which to organize
descriptive chemistry
• they provide an intellectual satisfaction derived from
constructing models that accurately reflect the
behavior of chemical systems
• they are tools with which to search for new information
and new understanding
6-14
Electrophilic Additions
•
•
•
•
•
hydrohalogenation using HCl, HBr, HI
hydration using H2O in the presence of H2SO4
halogenation using Cl2, Br2
halohydrination using HOCl, HOBr
oxymercuration using Hg(OAc)2, H2O followed by
reduction
6-15
Addition of HX
 Carried
out with pure reagents or in a polar
solvent such as acetic acid
Br H
CH3 CH=CH2
Propene
 Addition
+ HBr
H
Br
CH3 CH-CH2 + CH3 CH-CH2
2-Bromopropane 1-Bromopropane
(not observed)
is regioselective
• regioselective reaction: an addition or substitution
reaction in which one of two or more possible
products is formed in preference to all others that
might be formed
• Markovnikov’s rule: in the addition of HX, H2O, or ROH
to an alkene, H adds to the carbon of the double bond
having the greater number of hydrogens
6-16
HBr + 2-Butene
 A two-step mechanism
Step 1: proton transfer from HBr to the alkene gives a carbocation
intermediate
slow, rate
H
 
determining
CH3 CH=CHCH3 + H Br
CH3 CH-CHCH3 + Br
sec-Butyl cation
(a 2° carbocation
intermediate)
Step 2: reaction of the sec-butyl cation (an electrophile) with
bromide ion (a nucleophile) completes the reaction
+ CH3 CHCH2 CH3
Br
Bromide ion sec-Butyl cation
(a nucleophile) (an electrophile)
fast
Br
CH3 CHCH2 CH3
2-Bromobutane
6-17
HBr + 2-Butene
 An
energy diagram for the two-step addition of
HBr to 2-butene
• the reaction is exergonic
6-18
Carbocations


Carbocation: a species in which a carbon atom has only
six electrons in its valence shell and bears positive
charge
Carbocations are
• classified as 1°, 2°, or 3° depending on the number of
carbons bonded to the carbon bearing the positive
charge
• electrophiles; that is, they are electron-loving
• Lewis acids
6-19
Carbocations
• bond angles about a positively charged carbon are
approximately 120°
• carbon uses sp2 hybrid orbitals to form sigma bonds
to the three attached groups
• the unhybridized 2p orbital lies perpendicular to the
sigma bond framework and contains no electrons
6-20
Carbocation Stability
• a 3° carbocation is more stable than a 2° carbocation,
and requires a lower activation energy for its formation
• a 2° carbocation is, in turn, more stable than a 1°
carbocation,
• methyl and 1° carbocations are so unstable that they
are never observed in solution
6-21
Carbocation Stability
• relative stability
H
H
C+
H
Methyl
cation
(methyl)
H
CH3 C+
H
Ethyl
cation
(1°)
CH3
CH3
CH3 C+
CH3 C+
H
Isopropyl
cation
(2°)
CH3
tert-Butyl
cation
(3°)
Increasing carbocation stability
• methyl and primary carbocations are so unstable that
they are never observed in solution
6-22
Carbocation Stability
• we can account for the relative stability of
carbocations if we assume that alkyl groups bonded to
the positively charged carbon are electron releasing
and thereby delocalize the positive charge of the
cation
• we account for this electron-releasing ability of alkyl
groups by (1) the inductive effect, and (2)
hyperconjugation
6-23
The Inductive Effect
• the positively charged carbon polarizes electrons of
adjacent sigma bonds toward it
• the positive charge on the cation is thus localized over
nearby atoms
• the larger the volume over which the positive charge is
delocalized, the greater the stability of the cation
6-24
Hyperconjugation
• involves partial overlap of the -bonding orbital of an
adjacent C-H or C-C bond with the vacant 2p orbital of
the cationic carbon
• the result is delocalization of the positive charge
6-25
Addition of H2O
• addition of water is called hydration
• acid-catalyzed hydration of an alkene is regioselective;
hydrogen adds preferentially to the less substituted
carbon of the double bond
• HOH adds in accordance with Markovnikov’s rule
CH3 CH=CH2 + H2 O
Propene
CH3
CH3 C=CH2 + H2 O
2-Methylpropene
H2 SO4
OH H
CH3 CH-CH2
2-Propanol
CH3
CH3 C-CH2
HO H
2-Methyl-2-propanol
H2 SO4
6-26
Addition of H2O
• Step 1: proton transfer from H3O+ to the alkene
+
H O H
+
CH3 CHCH 3
:
CH3 CH= CH 2
:
+
slow, rate
determining
+
:O H
A 2o carbocation
intermediate
H
H
• Step 2: reaction of the carbocation (an electrophile)
with water (a nucleophile) gives an oxonium ion
CH3 CHCH 3
:
+
+
: O- H
fast
CH3 CHCH 3
O+
H
:
H
H
An oxonium ion
• Step 3: proton transfer to water gives the alcohol
H
H
+
CH3 CHCH 3 + H O H
: OH
H
:
O:
O+
:
H
:
H
fast
:
CH3 CHCH 3
6-27
Carbocation Rearrangements
 In
electrophilic addition to alkenes, there is the
possibility for rearrangement
 Rearrangement: a change in connectivity of the
atoms in a product compared with the
connectivity of the same atoms in the starting
material
6-28
Carbocation Rearrangements
• in addition of HCl to an alkene
Cl
+ HCl
3,3-Dimethyl1-butene
Cl
+
2-Chloro-3,3-dimethylbutane 2-Chloro-2,3-dimethylbutane
(the expected product; 17%)
(the major product; 83%)
• in acid-catalyzed hydration of an alkene
+ H2 O
3-Methyl-1-butene
H2 SO4
OH
2-Methyl-2-butanol
6-29
Carbocation Rearrangements
• the driving force is rearrangement of a less stable
carbocation to a more stable one
CH3
CH3 C- CHCH3 + : Cl :
:
+
:
Cl :
CH3
:
:
CH3 CCH= CH2 + H
H
3-Methyl-1-butene
slow, rate
determining
H
A 2° carbocation
intermediate
• the less stable 2° carbocation rearranges to a more
stable 3° one by 1,2-shift of a hydride ion
CH3
CH3 C- CHCH3
+
H
fast
CH3
CH3 C- CHCH3
+
H
A 3° carbocation
6-30
Carbocation Rearrangements
• reaction of the more stable carbocation (an
electrophile) with chloride ion (a nucleophile)
completes the reaction
CH 3
:
CH 3 C- CH 2 CH 3 + : Cl :
+
fast
CH 3
:
:
CH 3 C- CH 2 CH 3
: Cl :
2-Chloro-2-methylbutane
6-31
Addition of Cl2 and Br2
• carried out with either the pure reagents or in an inert
solvent such as CH2Cl2
Br Br
CH3 CH=CHCH3
2-Butene
+
Br2
CH2 Cl2
CH3 CH-CHCH3
2,3-Dibromobutane
• addition of bromine or chlorine to a cycloalkene gives
a trans-dihalocycloalkane
Br
+
Br2
Cyclohexene
CH2 Cl2
Br
+
Br
Br
trans-1,2-Dibromocyclohexane
(a racemic mixture)
• addition occurs with anti stereoselectivity; halogen
atoms add from the opposite face of the double bond
• we will discuss this selectivity in detail in Section 6.7
6-32
Addition of Cl2 and Br2
• Step 1: formation of a bridged bromonium ion
intermediate
Br
Br
C
C
Br
Br
C
C
C
Br
C
These carbocations are major
contributing structures
C
C
+ Br
-
The bridged bromonium
ion retains the geometry
6-33
Addition of Cl2 and Br2
• Step 2: attack of halide ion (a nucleophile) from the
opposite side of the bromonium ion (an electrophile)
opens the three-membered ring to give the product
Br
Br
C
C
C
C
Br
Br
-
Anti (coplanar) orientation
of added bromine atoms
C
C
C
C
Br
Br
-
Br
Newman projection
of the product
Br
Br
Br
Br
Anti (coplanar) orientation
of added bromine atoms
Br
Newman projection
of the product
6-34
Addition of Cl2 and Br2
• for a cyclohexene, anti coplanar addition corresponds
to trans diaxial addition
• the initial trans diaxial conformation is in equilibrium
with the more stable trans diequatorial conformation
• because the bromonium ion can form on either face of
the alkene with equal probability, both trans
enantiomers are formed as a racemic mixture
Br
+
Br2
Br
Br
Br
(1S,2S)-1,2-Dibromocyclohexane
Br
Br
Br
Br
(1R,2R)-1,2-Dibromocyclohexane
6-35
Addition of HOCl and HOBr
 Treatment
of an alkene with Br2 or Cl2 in water
forms a halohydrin
 Halohydrin: a compound containing -OH and -X
on adjacent carbons
CH3 CH=CH2 + Cl2 + H2 O
Propene
HO Cl
CH3 CH-CH2
+ HCl
1-Chloro-2-propanol
(a chlorohydrin)
6-36
Addition of HOCl and HOBr
• reaction is both regiospecific (OH adds to the more
substituted carbon) and anti stereoselective
• both selectivities are illustrated by the addition of
HOBr to 1-methylcyclopentene
Br2 / H2 O
OH
Br
1-Methylcyclopentene
+
OH
+ HBr
Br
H
H
2-Bromo-1-methylcyclopentanol
( a racemic mixture )
• to account for the regioselectivity and the anti
stereoselectivity, chemists propose the three-step
mechanism in the next screen
6-37
Addition of HOCl and HOBr
Step 1: formation of a bridged halonium ion intermediate
:
: Br :
: Br :
:
H
R
C
C
H - Br
H
:
: Br :
-
: Br :
C
C
H
H
R
H
bridged bromonium
ion
C
C
H
H
R
H
minor contributing
structure
Step 2: attack of H2O on the more substituted carbon
opens the three-membered ring
:
H O:
C
H
R
C
: Br :
C
H
C
+
H
H
O
:
H
H
R
:
: Br :
H
H
H
6-38
Addition of HOCl and HOBr
• Step 3: proton transfer to H2O completes the reaction
H
R
C
C
H
H
Br
C
+
O
• •
H
R
Br
H
H
H
O
• •
+ H3 O+
C
H
H
O H
 As
H
the elpot map on the next screen shows
• the C-X bond to the more substituted carbon is longer
than the one to the less substituted carbon
• because of this difference in bond lengths, the
transition state for ring opening can be reached more
easily by attack of the nucleophile at the more
substituted carbon
6-39
Addition of HOCl and HOBr
• bridged bromonium ion from propene
6-40
Oxymercuration/Reduction
 Oxymercuration
followed by reduction results in
hydration of a carbon-carbon double bond
• oxymercuration
OH
+ Hg(OAc) 2 + H2 O
1-Pentene
O
+ CH3 COH
HgOAc
An organomercury
compound
Mercury(II)
acetate
Acetic
acid
• reduction
OH
OH
NaBH4
HgOAc
H
2-Pentanol
O
+ CH3 COH + Hg
Acetic acid
6-41
Oxymercuration/Reduction
• an important feature of oxymercuration/reduction is
that it occurs without rearrangement
1 . Hg(OAc) 2 , H2 O
2 . NaBH4
OH
3,3-Dimethyl-2-butanol
3,3-Dimethyl-1-butene
• oxymercuration occurs with anti stereoselectivity
Hg(OAc) 2
H
H
Cyclopentene
H2 O
NaBH4
OH
H
H
HgOAc
(Anti addition of
OH and HgOAc)
OH
H
H
H
Cyclopentanol
6-42
Oxymercuration/Reduction
• Step 1: dissociation of mercury(II) acetate
• Step 2: formation of a bridged mercurinium ion
intermediate; a two-atom three-center bond
6-43
Oxymercuration/Reduction
• Step 3: regioselective attack of H2O (a nucleophile) on
the bridged intermediate opens the three-membered
ring
• Step 4: reduction of the C-HgOAc bond
6-44
Oxymercuration/Reduction
 Anti
stereoselective
• we account for the stereoselectivity by formation of
the bridged bromonium ion and anti attack of the
nucleophile which opens the three-membered ring
 Regioselective
• of the two carbons of the mercurinium ion
intermediate, the more substituted carbon has the
greater degree of partial positive character
• alternatively, computer modeling indicates that the CHg bond to the more substituted carbon of the bridged
intermediate is longer than the one to the less
substituted carbon
• therefore, the ring-opening transition state is reached
more easily by attack at the more substituted carbon
6-45
Hydroboration/Oxidation
 Hydroboration:
the addition of borane, BH3, to an
alkene to form a trialkylborane
H
H B
CH2 CH3
+ 3 CH2 = CH2
H
Borane
 Borane
CH3 CH2 B
CH2 CH3
Triethylborane
(a trialkylborane)
dimerizes to diborane, B2H6
2 BH 3
B2 H6
Borane
Diborane
6-46
Hydroboration/Oxidation
• borane forms a stable complex with ethers such as
THF
• the reagent is used most often as a commercially
available solution of BH3 in THF
2
: O:
+ B2 H6
Tetrahydrofuran
(THF)
2
+ :O BH3
BH3 • THF
6-47
Hydroboration/Oxidation
 Hydroboration
is both
• regioselective (boron to the less hindered carbon)
• and syn stereoselective
+
H
CH 3
1-Methylcyclopentene
BH 3
H
BR2
H3 C
H
(Syn addition of BH3)
(R = 2-methylcyclopentyl)
6-48
Hydroboration/Oxidation
• concerted regioselective and syn stereoselective
addition of B and H to the carbon-carbon double bond
 
H B
H
CH3 CH2 CH2 CH= CH2
B
CH3 CH2 CH2 CH-CH 2
• trialkylboranes are rarely isolated
• oxidation with alkaline hydrogen peroxide gives an
alcohol and sodium borate
R3 B + H2 O2 + NaOH
A trialkylborane
3 ROH + Na3 BO3
An alcohol
6-49
Hydroboration/Oxidation
 Hydrogen
peroxide oxidation of a trialkylborane
• step 1: hydroperoxide ion (a nucleophile) donates a
pair of electrons to boron (an electrophile)
R
R
+
R B
O-O-H
R
A trialkylborane Hydroperoxide ion
(an electrophile) (a nucleophile)
R B O O H
R
• step 2: rearrangement of an R group with its pair of
bonding electrons to an adjacent oxygen atom
R
R B O O H
R
R
R B O
+
-
O-H
R
6-50
Hydroboration/Oxidation
• step 3: reaction of the trialkylborane with aqueous
NaOH gives the alcohol and sodium borate
( RO) 3 B + 3NaOH
A trialkylborate
3ROH + Na3 BO3
Sodium borate
6-51
Oxidation/Reduction
 Oxidation:
the loss of electrons
• alternatively, the loss of H, the gain of O, or both
 Reduction:
the gain of electrons
• alternatively, the gain of H, the loss of O, or both
 Recognize
using a balanced half-reaction
1. write a half-reaction showing one reactant and its
product(s)
2. complete a material balance; use H2O and H+ in acid
solution, use H2O and OH- in basic solution
3. complete a charge balance using electrons, e-
6-52
Oxidation/Reduction
• three balanced half-reactions
OH
CH3 CH= CH2 + H2 O
Propene
CH3 CHCH3
2-Propanol
HO OH
CH3 CH= CH2 + 2 H2 O
Propene
CH3 CH= CH2 + 2 H+ + 2 e Propene
CH3 CHCH2 + 2 H+ + 2 e 1,2-Propanediol
CH3 CH2 CH3
Propane
6-53
Oxidation with OsO4
 OsO4
oxidizes an alkene to a glycol, a compound
with OH groups on adjacent carbons
• oxidation is syn stereoselective
OsO4
O O
Os
O O
A cyclic osmate
OH
NaHSO3
H2 O
OH
cis-1,2-Cyclopentanediol
(a cis glycol)
6-54
Oxidation with OsO4
• OsO4 is both expensive and highly toxic
• it is used in catalytic amounts with another oxidizing
agent to reoxidize its reduced forms and, thus, recycle
OsO4
HOOH
Hydrogen
peroxide
CH3
CH3 COOH
CH3
tert-Butyl hydroperoxide
(t-BuOOH)
6-55
Oxidation with O3
 Treatment
of an alkene with ozone followed by a
weak reducing agent cleaves the C=C and forms
two carbonyl groups in its place
CH3
CH3 C= CHCH2 CH 3
2-Methyl-2-pentene
O
1 . O3
CH3 CCH3
2 . ( CH3 ) 2 S
Propanone
(a ketone)
O
+ HCCH 2 CH3
Propanal
(an aldehyde)
6-56
Oxidation with O3
• the initial product is a molozonide which rearranges to
an isomeric ozonide
CH 3 CH= CH CH 3
2-Butene
O3
O OO
CH 3 CH- CHCH3
A molozonide
H
O
H
O
CH 3 CH
C
C
( CH3 ) 2 S
CH 3
O O
Acetaldehyde
An ozonide
H3 C
6-57
Reduction of Alkenes
 Most
alkenes react with H2 in the presence of a
transition metal catalyst to give alkanes
+ H2
Cyclohexene
Pd
25°C, 3 atm
Cyclohexane
• commonly used catalysts are Pt, Pd, Ru, and Ni
• the process is called catalytic reduction or,
alternatively, catalytic hydrogenation
• addition occurs with syn stereoselectivity
6-58
Reduction of Alkenes
 Mechanism
of catalytic hydrogenation
6-59
Reduction of Alkenes
• even though addition syn stereoselectivity, some
product may appear to result from trans addition
CH3
CH3
H2 / Pt
CH3
1,2-Dimethylcyclohexene
CH3
+
CH3
70% to 85%
cis-1,2-Dimethylcyclohexane
CH3
30% to15%
trans-1,2-Dimethylcyclohexane
(racemic)
• reversal of the reaction after the addition of the first
hydrogen gives an isomeric alkene, etc.
CH3
CH3
1,2-Dimethylcyclohexene
H2 / Pt
H
CH3
H
Pt
H CH3
CH3
CH3
1,6-Dimethylcyclohexene
6-60
DH0 of Hydrogenation
 Reduction
of an alkene to an alkane is
exothermic
• there is net conversion of one pi bond to one sigma
bond
 DH0
depends on the degree of substitution
• the greater the substitution, the lower the value of DH°

DH0 for a trans alkene is lower than that of an
isomeric cis alkene
• a trans alkene is more stable than a cis alkene
6-61
DH0 of Hydrogenation
Ethylene
Structural
Formula
CH 2 =CH2
Propene
CH 3 CH=CH2
Name
DH°
[kJ (kcal)/m ol]
-137 (-32.8)
-126 (-30.1)
1-Butene
-127 (-30.3)
cis-2-Butene
-120 (-28.6)
trans-2-Butene
-115 (-27.6)
2-Methyl-2-butene
-113 (-26.9)
2,3-Dimethyl-2-butene
-111 (-26.6)
6-62
Reaction Stereochemistry
 In
several of the reactions presented in this
chapter, chiral centers are created
 Where one or more chiral centers are created, is
the product
•
•
•
•
one enantiomer and, if so, which one?
a pair of enantiomers as a racemic mixture?
a meso compound?
a mixture of stereoisomers?
 As
we will see, the stereochemistry of the
product for some reactions depends on the
stereochemistry of the starting material; that is,
some reactions are stereospecific
6-63
Reaction Stereochemistry
 We
saw in Section 6.3D that bromine adds to 2butene to give 2,3-dibromobutane
CH3 CH=CHCH3
2-Butene
+
Br2
CH2 Cl2
Br Br
CH3 CH-CHCH3
2,3-Dibromobutane
• two stereoisomers are possible for 2-butene; a pair of
cis,trans isomers
• three stereoisomers are possible for the product; a
pair of enantiomers and a meso compound
• if we start with the cis isomer, what is the
stereochemistry of the product?
• if we start with the trans isomer, what is the
stereochemistry of the product?
6-64
Bromination of cis-2-Butene
• reaction of cis-2-butene with bromine forms bridged
bromonium ions which are meso and identical
6-65
Bromination of cis-2-Butene
• attack of bromide ion at carbons 2 and 3 occurs with
equal probability to give enantiomeric products as a
racemic mixture
6-66
Bromination of trans-2-Butene
• reaction with bromine forms bridged bromonium ion
intermediates which are enantiomers
6-67
Bromination of trans-2-Butene
• attack of bromide ion in either carbon of either
enantiomer gives meso-2,3-dibromobutane
6-68
Bromination of 2-Butene
 Given
these results, we say that addition of Br2
or Cl2 to an alkene is stereospecific
• bromination of cis-2-butene gives the enantiomers of
2,3-dibromobutane as a racemic mixture
• bromination of trans-2-butene gives meso-2,3dibromobutane
 Stereospecific
reaction: a reaction in which the
stereochemistry of the product depends on the
stereochemistry of the starting material
6-69
Oxidation of 2-Butene
• OsO4 oxidation of cis-2-butene gives meso-2,3butanediol
H3 C
H
H
2
C
H
H3 C
2
3
C
C
H
CH3
cis-2-Butene
(achiral)
OsO4
3
C
CH3
HO
OH
(2S,3R)-2,3-Butanediol
ROOH
identical;
a meso
compound
OH
HO
2
C
3
C
H
H
CH3
H3 C
(2R,3S)-2,3-Butanediol
6-70
Oxidation of 2-Butene
 OsO4
oxidation of an alkene is stereospecific
• oxidation of trans-2-butene gives the enantiomers of
2,3-butanediol as a racemic mixture (optically inactive)
H3 C
H
2
3
C
C
H
2
3
C
C
CH3
H3 C
H
trans-2-Butene
(achiral)
OsO4
CH3
H
HO
OH
(2S,3S)-2,3-Butanediol
ROOH
OH
HO
2
C
a pair of
enantiomers;
a racemic
mixture
3
C
CH3
H
H
H3 C
(2R,3R)-2,3-Butanediol
• and oxidation of cis-2-butene gives meso 2,3butanediol (also optically inactive)
6-71
Reaction Stereochemistry
 We
have seen two examples in which reaction of
achiral starting materials gives chiral products
• in each case, the product is formed as a racemic
mixture (which is optically inactive) or as a meso
compound (which is also optically inactive)
 These
examples illustrate a very important point
about the creation of chiral molecules
• optically active (enantiomerically pure) products can
never be produced from achiral starting materials and
achiral reagents under achiral conditions
• although the molecules of product may be chiral, the
product is always optically inactive (either meso or a
pair of enantiomers)
6-72
Reaction Stereochemistry
 Next
let us consider the reaction of a chiral
starting material in an achiral environment
• the bromination of (R)-4-tert-butylcyclohexene
• only a single diastereomer is formed
Br2
(R)-4-tert-Butylcyclohexene
Br
Br
redraw as
a chair
conformation
Br
Br
(1S,2S,4R)-1,2-Dibromo-4-tert-butylcyclohexane
• the presence of the bulky tert-butyl group controls the
orientation of the two bromine atoms added to the ring
6-73
Reaction Stereochemistry
 Finally,
consider the reaction of an achiral
starting material in an chiral environment
• BINAP can be resolved into its R and S enantiomers
PPh2
PPh2
BINAP
(S)-(-)-BINAP
[]D2 5 -223
(R)-(+)-BINAP
[]D2 5 +223
6-74
Reaction Stereochemistry
• treating (R)-BINAP with ruthenium(III) chloride forms a
complex in which ruthenium is bound in the chiral
environment of the larger BINAP molecule
• this complex is soluble in CH2Cl2 and can be used as a
homogeneous hydrogenation catalyst
(R)-BINAP + RuCl3
(R)-BINAP-Ru
• using (R)-BINAP-Ru as a hydrogenation catalyst, (S)naproxen is formed in greater than 98% ee
CH2
COOH
H3 CO
CH3
+ H2
(R)-BINAP-Ru
pressure
COOH
H3 CO
(S)-Naproxen
(ee > 98%)
6-75
Reaction Stereochemistry
• BINAP-Ru complexes are somewhat specific for the
types of C=C they reduce
• to be reduced, the double bond must have some kind
of a neighboring group that serves a directing group
(S)-BINAP-Ru
OH
H2
(E)-3,7-Dimethyl-2,6-octadien-1-ol
(Geraniol)
OH
(R)-3,7-Dimethyl-6-octen-1-ol
(R)-BINAP-Ru
OH
(S)-3,7-Dimethyl-6-octen-1-ol
6-76
Reactions
of Alkenes
End Chapter 6
6-77