Applications of Boron Chemistry:

Stereo- and Regioselective Reactions of Alkenes

Semester 1
Dr Boa, C120a, a.n.boa@hull.ac.uk

Contents Overview
1.
HYDROBORATION OF ALKENES AND ALKYNES
2.
OXIDATION OF ALKYL AND ALKENYLBORANES
3.
PROTONOLYSIS OF ALKYL AND ALKENYLBORANES
4.
HALOGENATION OF ALKYLBORANES
5.
AMINATION OF ALKYLBORANES
6.
FURTHER REACTIONS OF ALKENYLBORANES CIS ALKENES
7.
FURTHER REACTIONS OF ALKENYLBORANES TRANS ALKENES
8.
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)
Learning outcomes:
At the end of the course you should be able to:
1.
Formulate the alkyl- or alkenylborane product arising from reaction of borane,
or a borane derivative, with an alkene or alkyne.
2.
Formulate the product arising from oxidation, protonolysis, halogenation or
amination of an alkyl- or alkenylborane.
3.
Formulate the cis or trans alkene product arising from reaction of
alkenylboranes via a boronate intermediate.
4.
Predict the stereochemistry of the product(s) arising from reactions covered
(see LO1, 2 and 3) using reaction mechanisms to explain the stereochemical
outcome of the transformations.
5.
Show how silyl ethers can be used as hydroxyl protecting groups in organic
chemistry.
For a full set of notes and sample past paper questions (some with solutions) see
http://www.hull.ac.uk/php/chsanb/teaching.html

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

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 B
H

H B
H

H B
H

Me

S
Me

BH3.OEt2

BH3.THF

BH3.SMe2

17b

Alkylboranes and hydroboration or alkenes

The reactions of borane are dominated by those with alkenes in which the the C-H bond is replaced
with a C-R bond by addition of the B-H across the C=C of the alkene. This is known as hydroboration
of the alkene. You can consider this in simple terms by the replacement of the electron neutral H atom
with a +I alkyl group. With borane and simple unhindered alkenes multiple additions can take place in
which all B-H bonds are replaced with B-C bonds.

BH3

H2C

CH2

borane

BH2

H2C

alkylborane

CH2

H2C

BH

CH2

dialkylborane

trialkylborane

Hindered alkenes may undergo controlled mono- or dihydroboration reactions. Two useful alkylboranes
which will feature later in the course are shown below.

BH3.THF
0 oC

BH3.THF
BH2

thexylborane

0 oC

BH
2
disiamylborane
(Sia)2BH

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

H
B

intramolecular

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

BH2

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

Addition of BH3.THF across simple alkenes is regioselective, but even more so if a more hindered
alkyl borane is used.
B
9- B

BN
9 -B

B
99.9 : 0.1

BH

Cl

B
98.9 : 1.1

Cl
BH

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

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
D

BD2

D on same side as B
D

BD2

BD3.THF

BD2

H
H

half-chair conformation
viewed side on
D

D
B

H
H

Hydroboration of alkenes: examples

H
BH2

Me

BH2

BH2

BH2

BH3.THF

Me

19b

Me

The addition is syn

stereospecific, but
the borane adds
equally to each face.

BH2

BH2

A racemic mixture is
produced.

BH3.THF

less hindered face

CH3
H
more hindered face

H
BH2
CH3

BH3.THF

>

CH3
H
H
BH2

Addition to each
face is different.
Unequal amounts
of diasteroisomers
are produced.

regioselective and diastereoselective addition

Hydroboration of alkynes

20a

Hydroboration reactions of alkynes show the same regio- and sterochemical features
as seen with alkenes.
R

(Sia)2BH

B(Sia)2

9-BBN
C

H
H

R
monohydroboration of
terminal alkynes only occurs
in presence of excess alkyne

syn-stereospecific
B
H

regioselective
H
B

(Sia)2BH

larger

smaller
RL

RS

catecholborane
O
HB
O
regioselective

addition of borane (BH3) to

alkynes can form polymers
by multiple addition.
Et

O
H

9-BBN
O

B
RS

RL
H

Cl

thexylborane
regioselective

B thexyl

BH2
thexylborane

Et

Cl

note regiochemistry: H adds to the C atom stabilised in the transition state by the +I Et (not the -I Cl)

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

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

Reactions of alkylboranes - oxidation

21a

The oxidation reaction of alkylboranes proceeds via formation of a boronate complex.

Mechanism

boronate

NaOH
R H2O2

O
NaOH
+
HO-OH

HO O

R
R

B R

repeat

3x
R OH

NaOH
O

H2 O

OH
R migrates with its electron
pair. Thus the migratory
aptitude, in general, follows
the trend 1o > 2o > 3o

HO
O

O
HO
B
R O
O
R

The alkyl group migrates from B to O with retention of configuration.

Example

HO
R

O
R

OH
O
BR2
Me
anti

HO O

BR2
H

NaOH

Me
H

BR2
H

NaOH

Me

H2 O

OH

Me
anti

Reactions of alkylboranes - protonolysis

22a

The protonlysis of alkyl- and alkenylboranes using acetic acid produces alkanes or alkenes via a
stereospecific reaction with retention of configuration in the migrating R group.
Mechanism
R

R CH3CO2H

R
H3C

O
H3 C

OH

R
B R
O

B
+ H

H3C

AcO

AcO OAc R3
R2

B
O
H3C

R1
O

AcO

repeat

alkyl group migrates

with electron pair

R3
H

stereospecific
protonolysis

R2
R1

OAc

+
3 R

retention of
configuration
also works with
alkenyl boranes
(see slide 22b)

Example
Me

BH2
Me

BH3
THF

syn
Me adddition

H
CH3CO2H

Me (= AcOH)
H

Me

compare with
H2 / Pd-C

Me

Me

syn
hydrogenation

Me

Reactions of alkenylboranes - protonlysis

22b

The stereospecific protonlysis of boranes is a useful method for preparing isotopically labelled
compounds with control over which isomer is produced. This can be illustrated with the following
examples which are protonlysis reactions of alkenylboranes.

Me

BH3

H
Me

Me

BD3

D
Me

Me

BH3

H
Me

Me

BD3

D
Me

BH2

CH3CO2D

H
BD2

CH3CO2H

H
BH2

CH3CO2H

BD2
D

CH3CO2H

Me

Me

Me

Me

etc.

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 = 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

B
H H

NaOMe
H

Br
inversion of configuration

Br

Br

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

1. R2BH
2. NaOMe
3. CH3CO2H

Me

X = halogen

migration occurs with

retention of configuration in
the R group but inversion of
the alkenyl geometry

trans alkene
Mechanism

Me

Me

R2BH
Me

NaOMe

syn addition

B R

B R
R OMe

boronate formation

R
OMe

Me
H3COOC
MeO

MeO R

Io and 2o R groups
migrate preferentially

Me

CH3

Me

stereospecific
protonolysis

trans alkene

MeO

CH3CO2H

Synthesis of (E)-alkenes - continued

24b

This method is extremely useful for making alkenes if an unsymmetrical borane R1-BH-R2 is used and
you can control which R group migrates to the alkenylcarbon atom. With a thexylborane derivative this
is possible as the 3o alkyl thexyl group is less prone to migrate under these reaction conditions.
Synthesis of 1-halogenoalkynes
Br

Br
Br2

n-BuLi
Me

Me

Me

Br

Synthesis of unsymmetrical dialkylboranes

Me
e.g.

Me

BH3.THF
BH2

syn addition

thexyl
syn addition
regioselective

Putting it alltogether

thexyl
B

addition

B
H

thexyl
B

syn

H
Me

Br

Br
Me

thexyl

NaOMe
boronate
formation
and migration

CH3CO2H

B
OMe
Me

stereospecific
protonolysis

Me

Reactions of alkenylboranes - synthesis of (Z)-alkenes

25a

Hydroboration of alk-1-ynes, followed by reaction with NaOH/I2 gives rise to (Z)-alkenes

1. R2BH
2. NaOH, I2

Overall
Me

Me

Mechanism
Me
Me

Me

syn addition

OH

B R

R
R

HO
HO

OH
B R

B R

R
boronate

OH
Me

Me

NaOH

R2BH

side on view

I2
iodonium species

H
B OH
R
HO
anti elimination

OH
B

Me
H

Me
H

Me
R

R
OH

OH

B R

R
migration with inversion of
configuration at C

Synthesis of (Z)-alkenes - continued

25b
1

A before, this method would extremely useful for making alkenes if an unsymmetrical borane R BH-R2 was used and you could control which R group migrates to the carbon atom. Unfortunately
this is not possible as even the 3o thexyl group has been observed to migrate in this reaction. Thus
symmetrical boranes are used - if 'wastage' of one of the R groups can be justified.
t

Bu

H
t

BH3.THF
HB

Bu

NaOH, I2

Bu
H

In this e.g. you can 'afford to

waste' a simple cyclohexane ring

(Cy)2BH

An alternative approach is more 'long winded' going via a monobromo-monoalkylborane. Here only the
alkyl group can migrate thus making this route unambiguous.
Br2BH.SMe2

C11H23

H
C13H27

H
C8H17

housefly pheromone

LiAlH4

C11H23

BBr2
Br

NaOH, I2

C13H27

mono bromoborane
C11H23

cannot migrate
H
syn addition

can
migrate

C8H17

BHBr
+
C8H17

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

Si

320 kJ / mol

C F
450 kJ / mol

Si

Si

530 kJ / mol

810 kJ / mol

*R1 is now amenable to chemical transformation without interference by the OH group, for example:
unstablised ylids can act as bases

protected

R = SiR3

CH2=CHPh3
nucleophile

R3Si

R=H

O
R

CH2=CHPh3
basic ylid

Silyl ethers

26b

The following silyl ethers are commonly used as protecting groups

steric bulk

stability
Ph

Si O

Si O

Si O

Si O

Ph
ease of deprotection
t

trimethylsilyl
Me3Si-OR
TMS

butyldimethylsilyl
t
BuMe2Si-OR

TBDMS -or- TBS

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

Si

Si
HO

TfO

OTf

TfO = CF3SO2O (trifluoromethanesulfonate, or triflate)

Making and cleaving silyl ethers: protection and

deprotection

27a

The protection of alcohols as silyl ethers uses a silyl chloride and a base, commonly imidazole.
active silylating agent
R3Si
HN

Cl
HN

SiR3

imidazole

HO

HN

NH

HN

SiR3

R
R3Si

R3Si

HN

H
Deprotection of silyl ethers uses fluoride ion, commonly Bu4NF which is soluble in organic solvents.
This is also known as 'TBAF' - tetrabutyl ammonium fluoride. TMS and TES ethers are quite labile and
can be easily cleaved using using acids, sometimes too easily in the case of TMS ethers where very
weak acids or bases can lead to deprotection. TBAF is usually required for TBDPS or TIPS ethers.

810 kJ/mol

Bu4NF
SiR3

SiR3
+

SiR3
R

"H+"
work up

OH

F
F
This mechanism is often shown on paper as an SN2 process. The pentacoordinate Si is accessible due
to the longer C-Si bonds and also nucleophile attacks an accessible d orbital, not the C-O * orbital.

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

OTMS

[O]

TBAF

e.g. Swern
(but TMS quite labile)

THF / H2O

OH

TBDMSO

1 eq. TBAF

[O]

TBAF

THF / H2O
(lose more labile TMS)

e.g. Swern

THF / H2O

OH

OH

28a

Reactions of alkylboranes - summary

R1

BR2

R2
stereospecific
Oxidation
R1

regioselective
Protonolysis

syn addition

OH

R3

R1

H2O2, NaOH
retention

BR2

CH3CO2D

H
R3

retention

inversion
Br

R2

R3

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

R1

R2

stereospecific
via enol tautomer
O
R1

regioselective if R1< R2
cf. cis hydrogenation

syn addition

H2O2, NaOH

R2B

R2

R1

CH3CO2H

R2

if R1 = Hal
1. NaOMe
2.CH3CO2H

R1

R2

if R1 = H
NaOH, I2

R
R

Only one R group migrates

so using thexylborane
prevents wastage. The 3o
thexyl group migrates slower
than a 1o or 2o R group.

thexyl

B
H

R2

The thexyl group is known

to migrate in this reaction
so there is no advantage in
using unsymmetrical
boranes.