Download Applications of Phosphorus, Sulfur, Silicon and Boron Chemistry:

Applications of Phosphorus, Sulfur,
Silicon and Boron Chemistry:
Stereo- and Regioselective Synthesis and Reactions of Alkenes
Semester 1
Dr Andrew Boa, T: 01482 465022, E: [email protected]
Contents Overview
1.
SYNTHESIS OF ALKENES : A QUESTION OF REGIO- AND STEREOCONTROL
2.
SYN ELIMINATIONS - AMINE OXIDE, SULFOXIDE AND SELENOXIDE
ELIMINATIONS; CHUGAEV REACTION
3.
PETERSON OLEFINATION
4.
HORNER-WITTIG REACTION
5.
WITTIG REACTION - UNSTABILIZED AND STABILIZED YLIDS
6.
SCHLOSSER MODIFICATION OF THE WITTIG REACTION
7.
ARBUZOV REACTION
8.
HORNER-WADSWORTH-EMMONS REACTION
9.
SWERN OXIDATION AND RELATED PROCESSES
10. JULIA AND MODIFIED JULIA OLEFINATION
11. HYDROBORATION OF ALKENES AND ALKYNES
12. OXIDATION OF ALKYL AND ALKENYLBORANES
13. PROTONOLYSIS OF ALKYL AND ALKENYLBORANES
14. HALOGENATION OF ALKYLBORANES
15. AMINATION OF ALKYLBORANES
16. FURTHER REACTIONS OF ALKENYLBORANES – CIS ALKENES
17. FURTHER REACTIONS OF ALKENYLBORANES – TRANS ALKENES
18. SILYL ETHERS: HYDROXYL PROTECTING GROUPS
Suggested reading

Organic Chemistry, J. Clayden, N. Greeves, S. Warren and P. Wothers,
Oxford University Press. 1st Edition: Chapters 31, 46 and 47; 2nd Edition:
Chapter 27 and sections of Chapters 11 and 26 (and 17 good for revision).

Organic Synthesis: the Roles of Boron and Silicon, S.E. Thomas, (Oxford
Primer No. 1)

Organosulfur Chemistry, G.H. Whitham, (Oxford Primer No. 33)
Learning outcomes:
At the end of the course you should be able to:
1.
Formulate the P, S or Si product formed from a given set of reagents (as
covered in the course), e.g. synthesis of phosphonates, phosphonium salts,
ylids etc.
2.
Identify the alkene-forming reaction type for a given set of reagents, e.g.
“Peterson olefination” or “Wittig: stabilized ylid”
3.
Work out the structure of the alkene product(s) arising from given reagents
(see LO2)
4.
5.
6.
Predict the stereochemistry of the (major) alkene product (see LO3)
Rationalize your deductions using a mechanistic argument (see LO3 and 4)
Formulate the alkyl- or alkenylborane product arising from reaction of borane,
or a borane derivative, with an alkene or alkyne.
7.
Formulate the product arising from oxidation, protonolysis, halogenation or
amination of an alkyl- or alkenylborane.
8.
Formulate the cis or trans alkene product arising from reaction of
alkenylboranes via a boronate intermediate.
9.
Predict the stereochemistry of the product(s) arising from reactions covered
(see LO6, 7 and 8) using reaction mechanisms to explain the stereochemical
outcome of the transformations.
10. Show how silyl ethers can be used as hydroxyl protecting groups in organic
chemistry.
These notes, self-study workbook problems with answers, and sample past exam paper
questions (some with solutions) are available for download at:
http://www.hull.ac.uk/php/chsanb/teaching.html
Summary of key points
It is important to recognize the structure and names of the new functional groups, in particular
xanthate, phosphine oxide, phosphine, phosphonium salt, phosphite, phosphonate, sulfoxide and
sulfone. By doing so you will be able to spot names and structures and link this quickly to the
subsequent chemistry which will be studied.
Your notes
Summary of key points
It is really helpful use a molecular modelling kit to visualise the molecules in the Newman projection
and for comparison to flat 2D representations on paper (cf. 06520 Y2 S1 “Stereochemistry” course).
Do not get too “hung up” by correctly the identifying the threo and erythro isomers. Just looking at the
structure properly (with or without your model kit) will allow you to work out the answer.
Your notes
Summary of key points
In due course you will need to be sure you fully understand the difference in meaning of the terms
ending “-specific” and “-selective” (e.g. stereoselective vs. stereospecific).
Your notes
Summary of key points
E1 mechanism is two steps, stepwise reaction, cation formation followed by loss of proton. E2 is a
one step, concerted reaction, occurring via the lowest energy anti periplanar conformation. Both of
these have been studied before (cf. 06513 Y1 S2 “Substitution and Elimination” course).
Your notes
Summary of key points
The Ei elimination is a one-step, stereospecific concerted process, and occurs via less stable syn
periplanar conformation. In fact it is a concerted process, as covered in Dr Eames course in this
same module.
Your notes
Summary of key points
The Chugaev reaction is a thermal syn (Ei) elimination involving a xanthate group.
Your notes
Summary of key points
Sulfoxides and selenoxides can be made by the oxidation of the corresponding sulfide/selenide. The
later can be made by SN2 processes (cf. Y1 S2 06513) or enolate chemistry (cf. 06522 Y2 S2
“Bifunctional Chemistry”).
Your notes
Summary of key points
Thermal elimination of sulfoxides and selenoxides are syn–eliminations. Selenoxides with a βhydrogen are thermally unstable and readily undergo this process, sometimes as soon as they are
formed.
Your notes
Summary of key points
The Peterson olefination involves making an alkene by elimination of a β-trialkylsilyl alcohol. Do not
get confused with silyl ethers (slides 26/7) where the O is bonded directly to the Si. (NB olefin is an
old fashioned word for alkene, and so an olefination is a reaction making an alkene).
Your notes
Summary of key points
The synthesis of β-silyl alcohols is the first step of the Peterson reaction. This is basically chemistry
of the carbonyl group (cf. 06512 Y1 S2 “Carbonyl Chemistry”) involving addition of a carbon-based
nucleophile (organo- magnesium or lithium reagent) to a ketone or aldehyde.
Your notes
Summary of key points
For the Peterson elimination step, acidic conditions gives rise to an anti periplanar elimination, and
basic conditions a syn periplanar elimination. The alkene isomer formed [(E) or (Z)] depends on the
starting material isomer AND the conditions employed. You will not be expected to know how to
make a particular (single) isomer of a hydroxysilane.
Your notes
Summary of key points
A single diastereoisomer of the starting β-hydroxysilane gives a single isomer of the alkene, and the
other diastereoisomer will always give the other alkene isomer as product. Thus the elimination step
is stereospecific. The synthesis of the β-hydroxysilane is diastereoselective (mixtures of isomers
may be formed, whether it be 50:50 or 99:1) and so this step controls the (E)/(Z) ratio of the alkene
unless the isomers of the β-hydroxysilane are separated.
Your notes
Summary of key points
The key concepts of the Horner-Wittig reaction are very similar to the Peterson reaction under base
conditions. You will not be expected to know how to make a particular (single) isomer of a βhydroxyphosphine oxide, but may be asked to discuss this in very general terms.
Your notes
Summary of key points
The ‘trick’ to getting a pure alkene isomer is by choosing the best method to make the desired βhydroxy phosphine oxide isomer and, very probably, separation of minor isomers before elimination.
Your notes
Summary of key points
A phosphonium salt gives rise to an ylid upon treatment with a suitable base. These react with
aldehydes to form alkenes. The driving force of the reaction is the formation of the strong P=O bond
(phosphine oxide) in the by-product.
Your notes
Summary of key points
The (E):(Z) ratio of the alkene depends on the R group of the phosphorus ylid and to a lesser extent)
the conditions. The ylid may be described as stabilised or unstabilised (with a few in a few cases
being described as semi stabilised).
Your notes
Summary of key points
The Wittig reaction with an unstabilized ylid (presence of CH2 group next to the C=PPh3, i.e. no
conjugation) leads to the (Z) alkene major isomer via irreversible formation of four-membered
oxaphosphetane intermediate.
Your notes
Summary of key points
Reaction of ylids with ketones leads to lower stereoselectivity (and lower yields).
Your notes
Summary of key points
The Wittig reaction with a stabilized ylid (conjugation of C=P with unsaturation in R) leads to the (E)
alkene as the major product.
Your notes
Summary of key points
The threo betaine gives rise to the (E) alkene (and the erythro betaine the (Z) alkene), but these do
not equilibrate via the ylid. The presence of lithium ions affects the stereoselectivity of a reaction.
Your notes
Summary of key points
Stabilized ylids form (E)-alkenes and unstabilized form (Z)-alkenes, but in the presence of Li+ ions
increasing amounts of the amount of the other isomer may be formed.
Your notes
Summary of key points
The Wittig reaction with Schlosser modification lead to an unstabilised ylid generating the (E) alkene
as the major isomer via isomerisation of the betaine (NB betaine-Li ion complex not shown for clarity,
but presence is inferred).
Your notes
Summary of key points
Reduced yields and selectivity are seen when a tri-substituted alkene is being made (when a ketone
is used). Making tetrasubstituted alkenes by any phosphorus based method is often low yielding.
Your notes
Summary of key points
The Michaelis-Arbuzov reaction used to make phosphonates (phosphite + alkyl halides →
phosphonate).
Your notes
Summary of key points
The Horner-Wadsworth-Emmons (HWE) reaction uses a phosphonate instead of a phosphorus ylid
(Wittig). One advantage of the HWE over the Wittig reaction is the formation of a water soluble
phosphate salt as by-product (can be easily extracted).
Your notes
Summary of key points
HWE olefinations with simple phosphonates (OEt or OMe) generate almost exclusively (E) alkenes.
Other ‘R’ groups may generate a mixture of (E) and (Z) alkenes.
Your notes
Summary of key points
The Swern oxidation is a mild, metal-free oxidation of alcohols to aldehydes/ketones. (Over)oxidation
to the carboxylic acid is not observed.
Your notes
Summary of key points
The most common reagents/conditions for this (type of) reaction are (COCl)2 (oxalyl chloride) and
DMSO (dimethyl sulfoxide) at low T (see slide 14a).
Your notes
Summary of key points
The Julia olefination uses a sulfone in a multi-step (separate flaks for each step) process.
Your notes
Summary of key points
This method makes predominantly the (E) isomer of the alkene.
Your notes
Summary of key points
The Julia-Kocienski olefination uses a heteraromatic sulfone which leads, via a Smiles
rearrangement, directly to the alkene in one step (unlike the multistep Julia reaction).
Your notes
Summary of key points
The alkene isomer ratio depends on the selectivity of the initial addition to the aldehyde and you will
not be expected to predict or work out the alkene isomer ratio, other than the (E) isomer is generally
the major isomer.
Your notes
17a
Boron and borane
Boron is in group 13 of the periodic table and thus can form neutral compounds with 6-electrons in its
outer shell. Borane, BH3, is such an example and due to the empty p-orbital these compounds can act
as Lewis acids (cf. AlCl3)
H
B
H
H
H
H
B
H
H
B
H
H
Due to its electron deficiency borane forms the dimer diborane (B2H6). Two-electron three-centre
bonds (i.e bridging hydrogen atoms) are used to explain the bonding in this species.
Borane is also commercially available in a variety of forms as a 'complex' with an electron pair donator
- i.e. a Lewis base. The coordinate bond is formed between the vacant 2p oribtal of boron and the lone
pair of a small molecule such as an ether - e.g. diethyl ether or THF (tetrahydrofuran).
H
H
H
H B
H
H B
H
H B
H
O
O
S
Me
Me
BH3.OEt2
BH3.THF
BH3.SMe2
Summary of key points
Borane or diborane? In text books, papers (or exam questions!) this reagent may mentioned in either
monomeric or dimeric form, but you can treat it as the same. Also, for the purposes of the “paper
chemistry” in this course, borane complexed with another reagent (e.g. THF) can be considered as
just another source of borane.
Your notes
Summary of key points
Borane reacts with alkenes to form alkyl boranes. The more hindered an alkene the more likely it will
undergo controlled mono- or dihydroboration reaction. In the presence of excess borane, the mono
adduct can be assumed to be the major (only) product formed.
Your notes
Hydroboration of dienes
18a
Borane can also react with dienes to form cyclic boron compounds.
9-borabicyclo[3.3.1]nonane
BH3.THF
0 oC
BH adds across
2nd C=C
intermolecular
BH2
intramolecular
H
B
+
BH
9-BBN
cycloocta-1,5-diene
heat
H
B
9-BBN
BH
9-BBN is another commercially
available important borane which will
be encountered during the course.
Mono alkyl boranes can also react with dienes to form trialkylboranes. Here the examples are reactions
of thexylborane with acyclic dienes:
BH2
B
BH2
B
Summary of key points
Borane can also react with dienes to form cyclic boron compounds (as long as the ring size is
reasonable).
Your notes
Regiochemistry of alkene hydroboration
18b
The regiochemical outcome of the hydroboration reaction is that the boron adds preferentially to the
least hindered carbon of the C=C bond.
BH3.THF
BH2 >>>
0 oC
H
BH2
H
Addition of BH3.THF across simple alkenes is regioselective, but even more so if a more hindered
alkyl borane is used.
B
9- B
N
BN
9 -B
B
99.9 : 0.1
BH
3
Cl
B
98.9 : 1.1
Cl
BH
3
H2 B
H2 B
Cl
60 : 40
94 : 6
Electronic factors also play a role in the regiochemical outcome of the reaction. As can be seen
below, there is build up of positive charge on the more substituted carbon in the transition state.
cf. Markovnikov
addition of HX
to alkenes
+ H
H2B
+
-
H
H2 B
Summary of key points
The addition of a borane across an alkene is regioselective in which the boron atom adds
preferentially to the least hindered carbon of the C=C bond. However there is also an “electronic
factor”, which may be significant when the alkene has an electron withdrawing or donating group
directly attached. If an alkyl borane is used, especially hindered ones, then the regioselectivity is
often much greater.
Your notes
Stereochemistry of alkene hydroboration
19a
The addition of a B-H across a carbon-carbon double (or triple) bond is a concerted process. The
addition has been shown to be syn-stereospecific with the use of deuterated boranes or alkenes.
BH3.THF
BD3.THF
H
H
BH2
H
H
H
D
BD2
D on same side as B
D
BD3.THF
D
BD2
BD2
H
H
H
H
half-chair conformation
viewed side on
D
D
B
D
D
D
H
B
H
D
H
H
Summary of key points
The addition of a B-H across a carbon-carbon double (or triple) bond is a concerted, syn addition
process.
Your notes
Hydroboration of alkenes: examples
H
BH2
Me
H
H
BH2
+
H
BH2
H
BH2
BH3.THF
Me
19b
H
Me
H
H
The addition is syn
stereospecific, but
the borane adds
equally to each face.
BH2
BH2
H
H
A racemic mixture is
produced.
BH3.THF
+
less hindered face
CH3
H
more hindered face
H
BH2
CH3
BH3.THF
H
>
CH3
H
H
BH2
Addition to each
face is different.
Unequal amounts
of diasteroisomers
are produced.
regioselective and diastereoselective addition
Summary of key points
The hydroboration is syn stereospecific. The borane and hydrogen always add to the same face of
the alkene, so I f the alkene has two identical faces then this can lead to a racemic mixture. However,
if the alkene faces are different [e.g. when the alkene contains nearby stereogenic (chiral) centres]
then addition to one face of the alkene may be preferred (diastereoselectivity).
Your notes
Summary of key points
Hydroboration of alkynes is a regioselective and stereospecific syn addition. Monohydroboration of
terminal alkynes occurs smoothly only in presence of excess alkyne, and using borane leads to
polymers (unhindered double addition to the triple bond).
Your notes
Reactions of alkylboranes
20b
The carbon boron bond in alkylboranes may be cleaved in a variety of ways. Coupling the alkene
hydroboration with further reaction provides a range of very useful functional groups interconversions.
Oxidation
R3 B
Examples
H2O2, NaOH
BR2
3 x R-OH
Me
H2O2, NaOH
retention of
configuration
OH
Me
Protonolysis
R3 B
CH3CO2H
BR2
3 x R-H
Me
CH3CO2D
retention
D
Me
Halogenation
R3 B
NaOMe, X2
BR2
3 x R-X
Me
NaOMe, Br2
inversion
Br
Me
Amination
R3 B
NH2Cl
BR2
2 x R-NH2
Me
NH2Cl
retention
NH2
Me
Summary of key points
There are many possible reactions of alkylboranes, and this just covers a few examples. There is no
getting around having to learn the reagents to recognise these processes. Once this is done you will
need to be able to note which proceed with retention of configuration and which with inversion of
configuration.
Your notes
Reactions of alkylboranes - oxidation
21a
The oxidation reaction of alkylboranes proceeds via formation of a boronate complex.
Mechanism
R
B
boronate
NaOH
R H2O2
R
R
O
NaOH
+
HO-OH
HO O
B
R
R
R
R
B R
O
repeat
B
R
O
O
3x
R OH
NaOH
O
H2 O
R
OH
R migrates with its electron
pair. Thus the migratory
aptitude, in general, follows
the trend 1o > 2o > 3o
HO
O
R
O
HO
B
R O
O
R
The alkyl group migrates from B to O with retention of configuration.
Example
R
HO
R
O
B
R
O
R
OH
O
BR2
Me
anti
HO O
BR2
H
NaOH
Me
H
O
H
BR2
H
NaOH
Me
H2 O
OH
Me
anti
Summary of key points
Oxidation of alkylboranes proceeds via formation of a boronate complex. As you will see, many
reactions start this way when the electron poor boron is in the presence of MeO- or HO-.The alkyl
group migrates from B to O with retention of configuration.
Your notes
Summary of key points
Oxidation of alkenylboranes is just like that for alkylboranes, however you need to remember the enol
tautomerisation to the more stable keto form at the end (cf. 06522 Y2 S2 “Bifunctional Chemistry”).
Your notes
Summary of key points
Protonolysis of alkylboranes is a stereospecific process. The alkyl group migrates with its electron
pair so there is no change in spatial orientation in going from the C-B to C-H structures.
Your notes
Summary of key points
Protonolysis of alkenyboranes is also stereospecific, and so the combined hydroboration/protonolysis
sequence is a useful way to make alkenes of fixed geometry.
Your notes
Reactions of alkylboranes - halogenation
23a
Carbon-boron bonds are not usually cleaved as easily as seen in protonolysis. As found in the
oxidation reaction, however activation of the C-B bond can be acheived by making a boronate
complex. This can be seen in the halogenation reactions below.
Example
NaOMe
BH3.THF
BH2
X
X = I, Br
Br
H2B
X2
Mechanism
OMe
OMe
BH2
BH2
Br
OMe
Br
Stereochemical implications - this reaction proceeds with inversion of configuration at the C-B centre.
OMe
BH2
Br2
NaOMe
H
B
H
 H
H
Br

Br
Br
H
inversion of configuration
Summary of key points
Activation of the C-B bond is achieved by making a boronate complex. The reaction proceeds with
inversion of configuration at the C-B centre and so is different from the other reactions looked at.
Your notes
Summary of key points
In amination of alkylboranes the activation of the C-B bond is achieved by forming a boronate-type
complex. The reaction proceeds with retention of configuration in the intramolecular migration step.
With trialkylboranes the reaction stops at the second amination so only 2 moles of amine can be
made.
Your notes
Reactions of alkenylboranes - synthesis of (E)-alkenes
24a
Hydroboration of 1-haloalk-1-ynes, followed by reaction with NaOMe followed by acetic acid gives
rise to (E)-alkenes via a R-B to R-C migration.
Overall
Me
X
1. R2BH
2. NaOMe
3. CH3CO2H
Me
H
H
R
X = halogen
migration occurs with
retention of configuration in
the R group but inversion of
the alkenyl geometry
trans alkene
Mechanism
Me
Me
X
R2BH
Me
C
C
X
syn addition
X
NaOMe
H
B R
boronate formation
B R
R OMe
H
R
OMe
Me
H3COOC
MeO
B
R
H
H
R
trans alkene
Io and 2o R groups
migrate preferentially
MeO R
Me
H
B
H
R
CH3
O
O
MeO
CH3CO2H
Me
B
H
R
R
stereospecific
protonolysis
Summary of key points
Hydroboration of 1-haloalk-1-ynes can be used to make (E)-alkenes. The reaction could be viewed
as the boron being used to link together alkenyl and alkyl fragments in the trans configuration.
Your notes
Summary of key points
The migratory aptitude (3°<2°<1°) of alkyl groups in boronate complexes means that when
unsymmetrical boroalkanes are used control is possible and single products can be made.
Thexylborane is a common starting boroalkane for this reason.
Your notes
Reactions of alkenylboranes - synthesis of (Z)-alkenes
25a
Hydroboration of alk-1-ynes, followed by reaction with NaOH/I2 gives rise to (Z)-alkenes
Overall
Me
H
1. R2BH
2. NaOH, I2
Me
R
H
H
Mechanism
Me
Me
C
C
H
H
Me
H
OH
B R
H
R
H
H
HO
HO
B
R
B R
OH
B R
R
I2
iodonium species
I
R
H
B OH
R
HO
anti elimination
Me
H
I
Me
H
H
OH
B
Me
R
H
R
OH
I
H
OH
B R
R
migration with inversion of
configuration at C
Summary of key points
Hydroboration of alkynes, followed by reaction with NaOH/I2 give rise to (Z)-alkenes.
Your notes
H
H
R
boronate
OH
R
Me
NaOH
R2BH
syn addition
Me
side on view
H
Summary of key points
Using dialkylboranes one R group is wasted. So if using symmetrical dialkylboranes it is best if the R
groups are simple (e.g. cyclohexyl, R = Cy). Otherwise bromoboranes may be used as the bromine
does not migrate.
Your notes
Silyl ethers: temporary hydroxyl protecting groups
26a
Silicon is a versatile element in organic chemistry, as typified by the Peterson reaction seen before.
One ubiquitous application is the use of silyl ethers for the temporary protection of hydroxyl (alcohol/
phenol) groups when the presence of a free alcohol may interfere with a chemical transformation.
alcohol
R1 OH
silyl ether *
R3SiCl
R1 O
Bu4NF
R1 OH
SiR3
protection
deprotection
This protection / deprotection chemistry takes advantage of the particularly strong Si-O and S-F bonds.
The relevant bond dissociation energies are shown below.
C Si
320 kJ / mol
C C
335 kJ / mol
C
O
Si
320 kJ / mol
C F
450 kJ / mol
Si
Si
530 kJ / mol
F
810 kJ / mol
*R1 is now amenable to chemical transformation without interference by the OH group, for example:
protected
O
R3Si
unstablised ylids can act as bases
R = SiR3
CH2=CHPh3
nucleophile
R=H
O
R
O
CH2=CHPh3
basic ylid
O
O
Summary of key points
Silyl ethers can be used for temporary protection of hydroxyl (alcohol/phenol) groups. They can be
added and removed in high yield and under mild conditions.
Your notes
Silyl ethers
26b
The following silyl ethers are commonly used as protecting groups
steric bulk
stability
Ph
Si O
R
Si O
R
Si O
R
Si O
R
Ph
ease of deprotection
t
trimethylsilyl
Me3Si-OR
TMS
butyldimethylsilyl
t
BuMe2Si-OR
TBDMS -or- TBS
t
butyldiphenylsilyl
t
BuPh2Si-OR
triisopropylsilyl
i
Pr3Si-OR
TBDPS
TIPS
Also encountered are triethylsilyl, TES, and dichlorosilanes which can be used for protecting 1,2-diols
HO
O
O
Si
Si
HO
TfO
OTf
O
O
TfO = CF3SO2O (trifluoromethanesulfonate, or triflate)
Summary of key points
The most commonly used protecting groups are TMS, TBDMS (or TBS) and TBDPS. Increasing
steric hindrance leads to greater stability of the silyl ether, this is counterbalanced by requiring more
forcing conditions for the deprotection.
Your notes
Summary of key points
Protection of alcohols as silyl ethers uses a silyl chloride and a base (commonly imidazole, which
also acts as a catalyst). Deprotection of silyl ethers uses either acid, or fluoride ion (Bu4NF also
known as TBAF) as the Si-F bond is very strong.
Your notes
Selective protection using silyl ethers
27b
Silyl chlorides, especially bulky TBDPSCl, TIPSCl and TBDMSCl, can be used to selectively protect
1o alcohols in the presence of 2o or 3o alcohols. This can be illustrated in the following example,
showing how polyfunctional molecules may be selectively manipulated with the correct protection
strategy.
OH O
OH
OH
O
OH
?
2o alcohol
OH
?
1o alcohol
OH
OH
OTMS
TMS-Cl
imidazole
TBDMS-Cl
imidazole
TBDMSO
OTMS
TBDMSO
O
OTMS
[O]
TBAF
e.g. Swern
(but TMS quite labile)
THF / H2O
OH
TBDMSO
O
1 eq. TBAF
[O]
TBAF
THF / H2O
(lose more labile TMS)
e.g. Swern
THF / H2O
O
OH
OH
O
Summary of key points
Judicious choice of silyl ethers means that selective protection (and deprotection) may be achieved.
Bulky silyl chlorides (TBDPSCl, TIPSCl and TBDMSCl) can be used to selectively protect 1° alcohols
in the presence of 2° and 3° alcohols.
Your notes
28a
Reactions of alkylboranes - summary
R1
BR2
R2
stereospecific
Oxidation
R1
R
2
regioselective
Protonolysis
syn addition
OH
R
H
R3
R1
H2O2, NaOH
retention
3
R
2
BR2
CH3CO2D
H
R3
retention
inversion
Br
R2
R3
D
R2
R3
NH2Cl
NaOMe, Br2
R1
R1
retention
reactions involve formation
of a boronate intermediate
Halogenation
R1
NH2
R2
R3
Amination
28b
Reactions of alkenylboranes - summary
R2 B
H
R1
R2
stereospecific
via enol tautomer
O
R1
regioselective if R1< R2
cf. cis hydrogenation
syn addition
H2O2, NaOH
R2B
R2
H
R1
CH3CO2H
R2
if R1 = Hal
1. NaOMe
2.CH3CO2H
H
H
R1
R2
if R1 = H
NaOH, I2
R
R
2
Only one R group migrates
so using thexylborane
prevents wastage. The 3o
thexyl group migrates slower
than a 1o or 2o R group.
thexyl
R
B
H
R
R2
The thexyl group is known
to migrate in this reaction
so there is no advantage in
using unsymmetrical
boranes.