Page 696 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

678 The rates for the reaction of several aromatic ketones with alkyllithium reagents
have been examined. The reaction of 2,4-dimethyl-4’-(methylthio)benzophenone with
CHAPTER 7 methyl lithium in ether exhibits the rate expression
Addition, Condensation
and Substitution Rate = k MeLi 1/4 ketone
Reactions of Carbonyl
Compounds
This is consistent with a mechanism in which monomeric methyllithium, in equilibrium
with the tetramer, is the reactive nucleophile. 80 Most other studies have indicated
considerably more complex behavior. The rate data for reaction of 3-methyl-1-phenyl-
1-butanone with s-butyllithium and n-butyllithium in cyclohexane can be fit to a
mechanism involving product formation both through a complex of the ketone with
81
alkyllithium aggregate and by reaction with dissociated alkyllithium. Initial formation
of a complex is indicated by a shift in the carbonyl absorption band in the infrared
spectrum. Complex formation presumably involves a Lewis acid-base interaction
between the lithium ions and carbonyl oxygen in the alkyllithium cluster. In general
terms, it appears likely that alkyllithium reagents have the possibility of reacting
through any of several aggregated forms.
MO modeling (HF/3-21G) of the reaction of organolithium compounds with
carbonyl groups has examined the interaction of formaldehyde with the dimer of
methyllithium. The reaction is predicted to proceed by initial complexation of the
carbonyl group at lithium, followed by a rate-determining formation of the new carbon-
carbon bond. The cluster then reorganizes to incorporate the newly formed alkoxide
ion. 82 The TS is reached very early in the second step with only slight formation of
the C−C bond. This feature is consistent with the fast and exothermic nature of the
addition step.
H H H H
H H H H H H H H
C C C C
H
C O + Li Li H O Li Li H O Li Li Li Li
H C C
C C C O
H H H H H H H H H H
H H H
H H
H

The kinetics of addition of alkyllithium reagents to esters has been studied using a
83
series of ethyl benzoates. The rates show a rather complex dependence on both alkyl-
lithium concentration and the nature of aryl substituents. The rapid formation of an
initial ester-alkyllithium complex can be demonstrated. It is believed that product can
be formed by reaction with aggregated or monomeric alkyllithium reagent. N,N,N,N-
Tetramethylethylenediamine greatly accelerates the reaction, presumably by dissoci-
ating the organometallic aggregate (see Section 6.1).

.
(RLi) n + n TMEDA n/2 [(RLi) TMEDA]
2
OR'
.
.
+.
[(RLi) TMEDA] + PhCO R' Ph O Li RLi (TMEDA)
–
2
2
R
80
S. G. Smith, L. F. Charbonneau, D. P. Novak, and T. L. Brown, J. Am. Chem. Soc., 94, 7059 (1972).
81
M. A. Al-Aseer and S. G. Smith, J. Org. Chem., 49, 2608 (1984).
82 E. Kaufmann, P. v. R. Schleyer, K. N. Houk, and Y.-D. Wu, J. Am. Chem. Soc., 107, 5560 (1985).
83
M. A. Al-Aseer, B. D. Allison, and S. G. Smith, J. Org. Chem., 50, 2715 (1985).