Page 670 - Advanced Organic Chemistry Part B - Reactions & Synthesis

reaction depends on the stability of the dilithio adduct that is formed. This intermediate 645
does not break down until hydrolysis, at which point the ketone is liberated. Some
examples of this reaction are shown in Section B of Scheme 7.4. SECTION 7.2
Reactions of
–
O O Li + OH O Organomagnesium and
Organolithium
H + Compounds
–
–
RLi + R′CO Li + R′CO Li + R′COH RCR′
H O
2
R R
A study aimed at optimizing yields in this reaction found that carbinol formation was
a major competing process if the reaction was not carried out in such a way that all
of the lithium compound was consumed prior to hydrolysis. 113 Any excess lithium
reagent that is present reacts extremely rapidly with the ketone as it is formed by
hydrolysis. Another way to avoid the problem of carbinol formation is to quench the
reaction mixture with trimethylsilyl chloride. 114 This procedure generates the disilyl
acetal, which is stable until hydrolysis.
O
1) 4 equiv MeLi
H
CO 2 CCH 3
2) TMS-Cl
O, H +
3) H 2 92%
The synthesis of unsymmetrical ketones can be carried out in a tandem one-pot process
by successive addition of two different alkyllithium reagents. 115
O
R'Li H O
2
–
RLi + CO 2 RCO Li + RCR′
2
H +
N-Methyl-N-methoxyamides are also useful starting materials for preparation of
ketones Again, the reaction depends upon the stability of the tetrahedral interme-
diate against elimination and a second addition step. In this case chelation with the
N-methoxy substituent is responsible.

O – O Li +
R′ O
+ R′Li +
RCNCH 3 H , H O
OCH 3 2
R N RCR′
OCH 3
CH 3
Scheme 7.4 illustrates some of the important synthetic reactions in which
organolithium reagents act as nucleophiles. The range of reactions includes S 2-type
N
alkylation (Entries 1 to 3), epoxide ring opening (Entry 4), and formation of alcohols
by additions to aldehydes and ketones (Entries 5 to 10). Note that in Entry 2, alkylation
takes place mainly at the -carbon of the allylic system. The ratio favoring -alkylation

113 R. Levine, M. J. Karten, and W. M. Kadunce, J. Org. Chem., 40, 1770 (1975).
114 G. M. Rubottom and C. Kim, J. Org. Chem., 48, 1550 (1983).
115
G. Zadel and E. Breitmaier, Angew. Chem. Int. Ed. Engl., 31, 1035 (1992).