6. Hydroboration/Oxidation
‹ Hydroboration:
The addition of borane, BH3, to
an alkene to form a trialkylborane.
‹ Borane
dimerizes to diborane, B2H6.
6-1
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.
6-2
Hydroboration/Oxidation
‹ Hydroboration
is both
• regioselective (boron bonds to the less hindered
carbon)
• and syn stereoselective
6-3
Hydroboration/Oxidation
• Concerted regioselective and syn stereoselective
addition of B and H to the carbon-carbon double bond.
• Trialkylboranes are rarely isolated.
• Oxidation with alkaline hydrogen peroxide gives an
alcohol and sodium borate.
6-4
Hydroboration/Oxidation
‹ Hydrogen
peroxide oxidation of a trialkylborane
• Step 1: Hydroperoxide ion (a nucleophile) donates a pair
of electrons to boron (an electrophile).
• Step 2: Rearrangement of an R group with its pair of
bonding electrons to an adjacent oxygen atom.
6-5
Hydroboration/Oxidation
• Step 3: Reaction of the trialkylborane with aqueous
NaOH gives the alcohol and sodium borate.
6-6
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-
6-7
Oxidation/Reduction
• Balanced half-reactions for the hydration, oxidation
and reduction of propene.
6-8
7. Oxidation with OsO4
‹ OsO4
oxidizes an alkene to a glycol, a compound
with OH groups on adjacent carbons.
• Oxidation is syn stereoselective.
6-9
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. Two commonly used oxidizing agents are
6-10
8. 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. In the following
example, the weak reducing agent is
dimethylsulfide, (CH3)2S.
6-11
Oxidation with O3
• The initial product is a molozonide which rearranges to
an isomeric ozonide.
6-12
9. Reduction of Alkenes
‹ Most
alkenes react with H2 in the presence of a
transition metal catalyst to give alkanes.
• Commonly used catalysts are Pt, Pd, Ru, and Ni.
• The process is called catalytic reduction or,
alternatively, catalytic hydrogenation.
• Addition occurs with syn stereoselectivity.
6-13
Reduction of Alkenes
‹ Mechanism
of catalytic hydrogenation.
6-14
Reduction of Alkenes
• Even
though
addition
occurs
with
syn
stereoselectivity, some product may appear to
result from trans addition.
• Reversal of the reaction after the addition of the first
hydrogen gives an isomeric alkene.
6-15
ΔH0 of Hydrogenation
6-16
ΔH0 of Hydrogenation
‹ Reduction
of an alkene to an alkane is
exothermic.
• There is net conversion of one pi bond to one sigma
bond.
‹ ΔH0
depends on the degree of substitution of the
carbon atoms of the double bond.
• The greater the substitution, the lower the value of ΔH°
‹
ΔH0 for a trans alkene is lower than that of an
isomeric cis alkene.
• A trans alkene is more stable than a cis alkene.
6-17
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.
6-18
Reaction Stereochemistry
‹ We
have seen that bromine adds to 2-butene to
give 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?
6-19
Bromination of cis-2-Butene
6-20
Bromination of cis-2-Butene
6-21
Bromination of trans-2-Butene
6-22
Bromination of trans-2-Butene
6-23
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.
6-24
Oxidation of 2-Butene
• OsO4 oxidation of cis-2-butene gives meso-2,3butanediol.
6-25
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).
• And oxidation of cis-2-butene gives meso 2,3butanediol (also optically inactive).
6-26
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).
6-27
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.
• The presence of the bulky tert-butyl group controls the
orientation of the two bromine atoms added to the
ring.
6-28
Reaction Stereochemistry
‹ Finally,
consider the reaction of an achiral
starting material in an chiral environment.
• BINAP [2,2-bis(diphenylphosphanyl)-1,1’-binaphthyl]
can be resolved into its R and S enantiomers.
6-29
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.
• Using (R)-BINAP-RuCl3 as a hydrogenation catalyst,
(S)-naproxen is formed in greater than 98% ee.
6-30
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.
In the following examples, the directing group is the
hydroxyl (OH) group.
6-31
Reactions
of Alkenes
End Chapter 6
6-32