Page 423 - Advanced Organic Chemistry Part B - Reactions & Synthesis

396 Pd 0 + H 2 Pd H 2 [Pd H] – + H +
II
II
II –
–
II
CHAPTER 5 PhCH OR + [Pd H] [PhCH Pd H] + OR
2
2
II –
Reduction of [PhCH Pd H] PhCH 3 + Pd 0
2
Carbon-Carbon Multiple
Bonds, Carbonyl
Groups, and Other The facile cleavage of the benzyl-oxygen bond has made the benzyl group a
Functional Groups
useful protecting group in multistep syntheses. A particularly important example is the
use of the carbobenzyloxy group in peptide synthesis. The protecting group is removed
by hydrogenolysis. The substituted carbamic acid generated by the hydrogenolysis
decarboxylates spontaneously to provide the amine (see Section 3.5.2).
O O
PhCH OCNHR PhCH 3 + HOCNHR CO 2 + H NR
2
2

5.3. Group III Hydride-Donor Reagents

5.3.1. Comparative Reactivity of Common Hydride Donor Reagents

Most reductions of carbonyl compounds are done with reagents that transfer a
hydride from boron or aluminum. The various reagents of this type that are available
provide a considerable degree of chemo- and stereoselectivity. Sodium borohydride
and lithium aluminum hydride are the most widely used of these reagents. Sodium
borohydride is a mild reducing agent that reacts rapidly with aldehydes and ketones
but only slowly with esters. It is moderately stable in hydroxylic solvents and can
be used in water or alcoholic solutions. Lithium aluminum hydride is a much more
powerful hydride donor, and it rapidly reduces esters, acids, nitriles, and amides, as
well as aldehydes and ketones. Lithium aluminum hydride is strongly basic and reacts
very rapidly (violently) with water or alcohols to release hydrogen. It must be used in
anhydrous solvents, usually ether or tetrahydrofuran. The difference in the reactivity of
these two compounds is due to properties of both the cations and the anions. Lithium
is a stronger Lewis acid than sodium and AlH − is a more reactive hydride donor
4
than BH . Neither sodium borohydride nor lithium aluminum hydride reacts with
−
4
isolated carbon-carbon double bonds. The reactivity of these reagents and some related
reducing reagents is summarized in Table 5.3.
The mechanism by which the Group III hydrides effect reduction involves
activation of the carbonyl group by coordination with a metal cation and nucleophilic
transfer of hydride to the carbonyl group. Hydroxylic solvents also participate in
the reaction, 59 and as reduction proceeds and hydride is transferred, the Lewis acid
character of boron and aluminum becomes a factor.
M + H M + + H
H H M M +
O H B – O R H Al – O
H B – R C H Al – O R R
H H R H H C
H R H H R H R

59
D. C. Wigfield and R. W. Gowland, J. Org. Chem., 42, 1108 (1977).