Page 669 - Advanced Organic Chemistry Part B - Reactions & Synthesis

644 force for cyclization is the formation of an additional C–C -bond and the formation
2
3
of a more stable (sp versus sp ) carbanion.
CHAPTER 7
Li
Organometallic
2
Compounds of Group I Li(CH 2 )nC C X (CH )n C C
and II Metals X
X = Ph, TMS; n = 2,3
(CH ) CH 3
2 3
) C C(CH ) CH C
Li(CH 2 4 2 3 3
Li
An alternative to preparation of organometallic reagents followed by reaction
with a carbonyl compound is to generate the organometallic intermediate in situ in
the presence of the carbonyl compound. The organometallic compound then reacts
immediately with the carbonyl compound. This procedure is referred to as the Barbier
reaction. 109 This technique has no advantage over the conventional one for most cases
for magnesium or lithium reagents. However, when the organometallic reagent is very
unstable, it can be a useful method. Allylic halides, which can be difficult to convert to
Grignard reagents in good yield, frequently give better results in the Barbier procedure.
Since solid metals are used, one of the factors affecting the rate of the reaction is the
physical state of the metal. Ultrasonic irradiation has been found to have a favorable
effect on the Barbier reaction, presumably by accelerating the generation of reactive
sites on the metal surface. 110
OH CH
CH 3 3
Mg
(CH ) CHCH CH O + CH 2 CCH Cl ether (CH ) CHCH CHCH C CH 2
3 2
2
2
2
3 2
2
92%
7.2.2.2. Reactions of Organolithium Compounds. The reactivity of organolithium
reagents toward carbonyl compounds is generally similar to that of Grignard reagents.
The lithium reagents are less likely to undergo the competing reduction reaction with
ketones, however.
Organolithium compounds can add to

-unsaturated ketones by either 1,2- or
1,4-addition. The most synthetically important version of the 1,4-addition involves
organocopper intermediates, and is discussed in Chap 8. However, 1,4-addition is
observed under some conditions even in the absence of copper catalysts. Highly
reactive organolithium reagents usually react by 1,2-addition, but the addition of small
amounts of HMPA has been found to favor 1,4-addition. This is attributed to solvation
of the lithium ion, which attenuates its Lewis acid character toward the carbonyl
oxygen. 111

Li Li HMPA
+
O O
R
R –

One reaction that is quite efficient for lithium reagents but poor for Grignard
reagents is the synthesis of ketones from carboxylic acids. 112 The success of the

109
C. Blomberg and F. A. Hartog, Synthesis, 18 (1977).
110
J.-L. Luche and J.-C. Damiano, J. Am. Chem. Soc., 102, 7926 (1980).
111 H. J. Reich and W. H. Sikorski, J. Org. Chem., 64, 14 (1999).
112
M. J. Jorgenson, Org. React., 18, 1 (1971).