Hydroboration–oxidation reaction

From Wikipedia, the free encyclopedia

In organic chemistry, the hydroboration–oxidation reaction is a two-step organic

reaction that converts an alkene into a neutral alcohol by the net addition of water
across the double bond.[1] The hydrogen andhydroxyl group are added in a syn
addition leading to cis stereochemistry. Hydroboration–oxidation is an anti-
Markovnikov reaction, with the hydroxyl group attaching to the less-substituted
carbon. The reaction was first reported by Herbert C. Brown in the late 1950s[2] and it
was recognized in his receiving the Nobel Prize in Chemistry in 1979.

The general form of the reaction is as follows:

Hydroboration–oxidation

where THF is tetrahydrofuran, the archetypal solvent used for this reaction. In the
first step, borane (BH3) adds to the double bond, transferring one hydrogen from
itself to the adjacent carbon. The second step substitutes the boron group BH2 with
the hydroxyl group, creating the final product.

The reaction described in the original 1957 Brown publication 1-hexene is converted
to 1-hexanol.[3]

Hexanol synthesis from 1-hexene Brown 1957

 Contents
[hide]

• 1 Hydroboration mechanism

• 2 Hydroboration–oxidation

• 3 Alkyne hydroboration

• 4 Organoborane reactions

• 5 References

• 6 External links

[edit]Hydroboration mechanism
Borane exists as a toxic, colorless gas called diborane (B2H6). In diborane, two
hydrogen atoms are each bonded to both boron atoms by single pairs of electrons
("three-center two-electron bonds"). Thisdelocalization satisfies the octet around
each boron and reduces the electrophilicity. That said, even diborane is
intensely Lewis acidic, because of its vacant p orbitals.
Because dimerization happens instantaneously, it is not possible to isolate pure
borane. However, when diborane is treated with an ether or amine, a stable complex
is formed, as the lone pair from the Lewis basic oxygen or nitrogen atom is donated
to the borane. These complexes act chemically like borane. Solutions of
BH3 complexes in THF or diethyl ether are commercially available and more easily
handled than diborane gas, and so are the more common form found in laboratories.
For simplicity in illustration, borane will be used instead of the borane–ether complex
in this article.

Diborane-ether complex

The addition of BH3 to the alkene is a concerted reaction, with multiple bond
formation and breaking occurring simultaneously. The intermediate step can be
visualized more clearly by a theoretical transition state.
 Hydroboration mechanism

Knowing that the group containing the boron will be replaced by a hydroxyl group, it
can be seen that the first step determines the regioselectivity. The hydroborane will
add to the alkene so that the boron always ends up on the lesser substituted carbon.
In the transition state, the more substituted carbon bears a partial positive charge (a
partial carbocation). As a general rule, carbocations that are more substituted
tolerate positive charge better than those that aren't. Had the hydroborane attacked
with the opposite orientation, the lesser substituted carbon would bear the (partial)
positive charge, which is electronically unfavorable. Hydroborane also tends to add
to the lesser substituted carbon because it is less sterically hindered.

Hydroborations are also stereoselective, with the new constituents adding in syn (on
the same face of the alkene). Thus 1-methylcyclopentene reacts with diborane
predominantly to the trans-alkane.[4]

Until all hydrogens attached to boron have been transferred away, the boron group
BH2 will continue adding to more alkenes. This means that one equivalent of
hydroborane will conduct the reaction with three equivalents of alkene. Furthermore,
it is not necessary for the hydroborane to have more than one hydrogen. Therefore,
BH3 can be better represented as R-BH, where R can represents the remainder of
the molecule. A widely used hydroboration reagent is 9-BBN which has just one
hydrogen at boron and the same applies for catecholborane.

[edit]Hydroboration–oxidation

In the second hydroboration–oxidation step, the

nucleophilic hydroperoxide anion attacks the boron atom. Alkyl migration to oxygen
gives the alkyl borane with retention of stereochemistry (in reality, the reaction
occurs via the trialkyl borate B(OR)3, rather than the monoalkyl borinic ester BH2OR).
 Hydroboration-oxidation mechanism

Oxymercuration–reduction is another reaction that converts an alkene into an

alcohol. Unlike hydroboration–oxidation, oxymercuration-reduction is not
stereospecific. Further, oxymercuration–reduction is a Markovnikov reaction.
Therefore, oxymercuration–reduction and hydroboration–oxidation are
complementary because they add with opposite regiochemistry.

[edit]Alkyne hydroboration
A hydroboration reaction also takes place on alkynes. Again the mode of action
is syn and secondary reaction products are aldehydes from terminal alkynes
and ketones from internal alkynes. In order to prevent hydroboration across both the
pi-bonds, a bulky borane like disiamyl (di-sec-iso-amyl) borane is used.[5]

[edit]Organoborane reactions
Amines can be obtained from the intermediate organoborane by action
of chloramine.[6] Reaction with iodine or bromine afford the corresponding alkyl
halides.[7][8] A carboxylic acid simply replaces the borane group by a proton.
[edit]
Grignard reaction
From Wikipedia, the free encyclopedia

The Grignard reaction (pronounced /ɡriɲar/) is an organometallic chemical reaction in which alkyl-
or aryl-magnesium halides (Grignard reagents) act as nucleophiles and attack electrophilic carbon
atoms that are present within polar bonds (e.g. in a carbonyl group as in the example shown below) to
yield a carbon-carbon bond, thus altering hybridization about the reaction center.[1] The Grignard
reaction is an important tool in the formation of carbon-carbon bonds[2][3] and for the formation of
carbon-phosphorus, carbon-tin, carbon-silicon, carbon-boron and other carbon-heteroatom bonds.

The nucleophilic organometallic addition reaction is irreversible due to the high pKa value of the
alkyl component (pKa = ~45). Such reactions are not ionic; the Grignard reagent exists as an
organometallic cluster (in ether).

The disadvantage of Grignard reagents is that they readily react with protic solvents (such as
water), or with functional groups with acidic protons, such as alcohols and amines. In fact,
atmospheric humidity in the lab can dictate one's success when trying to synthesize a Grignard
reagent from magnesium turnings and an alkyl halide. One of many methods used to exclude
water from the reaction atmosphere is to flame-dry the reaction vessel to evaporate all moisture,
which is then sealed to prevent moisture from returning. However, though the reagents still need
to be dry, ultrasound can allow Grignard reagents to form with less stringent regard to the
amount of water in the reaction mix by activating the surface of the magnesium such that it
consumes any water present.[4]

Another disadvantage of Grignard reagents is that they do not readily form carbon-carbon bonds
by reacting with alkyl halides via an SN2 mechanism.

Grignard reactions and reagents were discovered by and are named after the French
chemist François Auguste Victor Grignard (University of Nancy, France) who was awarded the
1912 Nobel Prize in Chemistry for this work.