Page 662 - Advanced Organic Chemistry Part B - Reactions & Synthesis

CH 3 CH 3 637

CH 3 MgBr + (CH O) SO 2 CH 3 CH 3 SECTION 7.2
2
3
Reactions of
CH 3 CH 3 Organomagnesium and
52–60% Organolithium
Ref. 88
Compounds

7.2.2. Reactions with Carbonyl Compounds

7.2.2.1. Reactions of Grignard Reagents. The most important reactions of Grignard
reagents for synthesis involve addition to carbonyl groups. The TS for addition of
Grignard reagents is often represented as a cyclic array containing the carbonyl group
and two molecules of the Grignard reagent. There is considerable evidence favoring
this mechanism involving a termolecular complex. 89
R′ R R′ O Mg R R′
C O Mg R′ R′ C O Mg R + MgX 2
R′ R Mg X R
X
X

When the carbonyl carbon is substituted with a potential leaving group, the tetrahedral
adduct can break down to regenerate a C=O bond and a second addition step can occur.
Esters, for example are usually converted to tertiary alcohols, rather than ketones, in
reactions with Grignard reagents.
O OMgX O
RMgX + R′COR″ R C OR″ RCR′ + R″OMgX
R′
O OMgX OH
fast H O
2
RCR′ + RMgX R CR′ R 2 CR′
2
Grignard reagents add to nitriles and, after hydrolysis of the reaction mixture, a
ketone is obtained, with hydrocarbons being the preferred solvent for this reaction. 90

NMgX O
H 2 O
RMgX + R′C N RCR′ RCR′

Ketones can also be prepared from acyl chlorides by reaction at low temperature using
an excess of acyl chloride. Tetrahydrofuran is the preferred solvent. 91 The reaction
conditions must be carefully controlled to prevent formation of tertiary alcohol by
addition of a Grignard reagent to the ketone as it is formed.

88 L. I. Smith, Org. Synth., II, 360 (1943).
89
E. C. Ashby, R. B. Duke, and H. M. Neuman, J. Am. Chem. Soc., 89, 1964 (1967); E. C. Ashby, Pure
Appl. Chem., 52, 545 (1980).
90 P. Canonne, G. B. Foscolos, and G. Lemay, Tetrahedron Lett., 21, 155 (1980).
91
F. Sato, M. Inoue, K. Oguro, and M. Sato, Tetrahedron Lett., 4303 (1979).