Ketones with Grignard reagents

The great synthetic utility of the reaction of alkyllithium and Grignard reagents with ketonic functions has been well documented.105 These reactions take place via the intermediacy of alkoxy derivatives formed by addition of the M—C bond across the C=0 function. Hence ketones, aldehydes and formaldehyde will lead to tertiary, secondary and primary alkoxides, respectively. This type of reactivity is known for a number of other carbanionic metal alkyl derivatives, both main group and transition metals, although the synthetic utility of the reactivity has in most cases not been well documented. 

This is a tertiary alcohol any one of the three alkyl groups might be added in the form of a Grignard reagent. We can propose three combinations of Grignard reagents with ketones ... 

Because of the considerable technical difficulties encountered when monitoring reaction mixtures of Grignard reagents with ketones (the reaction of methylmagnesium bromide and acetone was almost complete within 10 sec, even at — 15°C), it took a while before reports on such investigations appeared regularly. 

Ashby, E. C. A detailed description of the mechanism of reaction of Grignard reagents with ketones. Pure Appi. Chem. 1980, 52, 545-569. 

C-Alkylation of ketones. Fauvarque and Fauvarque1 found that the reaction of alkyl Grignard reagents with ketones in HMPT results in formation of magnesium enolates with elimination of the alkane. The enolates thus formed are readily... 

The final area that can be discussed involves the kinetics and mechanism of reactions of Grignard reagents with ketones, nitriles, Schiff bases, and weak acids. This area is intimately tied to the problem of the structure of the organomagnesium reagent itself and this in turn centers around the values of the equilibrium constants for the processes... 

Reductions in reaction yields by PEG and 18-crown-6 were observed by Yamazaki and coworkers for borohydride reductions of aldehydes and ketones in tetrahydrofuran and for the reaction of Grignard reagents with ketones and nitriles in benzene. The deleterious effect on the borohydride reductions was especially interes- 2 ting because of previous observations of enhancement by crown ethers. Yamazaki and coworkers found 18-crown-6 and PEG to have comparable... 

The adducts of allylic Grignard reagents with ketones can undergo isomerization to less hindered isomers by a reversal of the addition step. ... 

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