Page 462 - Advanced Organic Chemistry Part B - Reactions & Synthesis

reactant and reaction conditions. Three broad types of reactions can be recognized 435
and these are discussed separately. They include reactions in which the overall change
involves: (a) net addition of hydrogen, (b) reductive removal of a functional group, SECTION 5.6
and (c) formation of carbon-carbon bonds. Dissolving-Metal
Reductions

5.6.1. Addition of Hydrogen

5.6.1.1. Reduction of Ketones and Enones. Although the method has been supplanted
for synthetic purposes by hydride donors, the reduction of ketones to alcohols in
ammonia or alcohols provides mechanistic insight into dissolving-metal reductions.
The outcome of the reaction of ketones with metal reductants is determined by the
fate of the initial ketyl radical formed by a single-electron transfer. The radical inter-
mediate, depending on its structure and the reaction medium, may be protonated,
disproportionate, or dimerize. 209 In hydroxylic solvents such as liquid ammonia or
in the presence of an alcohol, the protonation process dominates over dimerization.
Net reduction can also occur by a disproportionation process. As is discussed in
Section 5.6.3, dimerization can become the dominant process under conditions in
which protonation does not occur rapidly.

OH O –
protonation R′ e – R′
2
RCH 2 C RCH C
SH
SH
H
O O – O – O –
e – dimerization
RCH 2 C R′ RCH 2 C R′ RCH 2 C C CH R
2
ketyl R′ R′
O – O –
disproportionation + CR′
RCH 2 C R′ RCH
H
-Unsaturated carbonyl compounds are cleanly reduced to the enolate of the
corresponding saturated ketone on reduction with lithium in ammonia. 210 Usually an
alcohol is added to the reduction solution to serve as the proton source.

O O –
O –
R C R R C R –
e – e
C C C C R CH CH C R
2
R H R H S H
As noted in Chapter 1, this is one of the best methods for generating a specific
enolate of a ketone. The enolate generated by conjugate reduction can undergo the
characteristic alkylation and addition reactions that are discussed in Chapters 1 and 2.
When this is the objective of the reduction, it is important to use only one equivalent
of the proton donor. Ammonia, being a weaker acid than an aliphatic ketone, does

209 V. Rautenstrauch and M. Geoffroy, J. Am. Chem. Soc., 99, 6280 (1977); J. W. Huffman and
W. W. McWhorter, J. Org. Chem., 44, 594 (1979); J. W. Huffman, P. C. Desai, and J. E. LaPrade, J.
Org. Chem., 48, 1474 (1983).
210
D. Caine, Org. React., 23, 1 (1976).