Regioselective α-Alkylation of Ketones via Magnesium Enamides

ketones - alkylation - magnesium enamides - imines

Significance

Alkylation of ketones via their metal enolates is one of the fundamental C-C bond-forming reactions in organic chemistry. However, the scope and selectivity of this process is often not satisfactory. The authors report herein a great improvement of this reaction, allowing to use usually unreactive primary and secondary alkyl chlorides and fluorides as electrophiles, with excellent regio- and often good stereoselectivity. Use of enantiopure benzyl halides afforded products with good enantioselectivities.

Comment

This elegant approach is based on the formation of highly nucleophilic magnesium enamides with inner coordination N-Mg bond. The imines are prepared by the usual way from the corresponding ketones. A large variety of electrophiles are now suitable for the alkylation. The reaction of α-phenylethyl chloride proceeds mostly with inversion, though racemization may take place under harsh conditions. Probably, an enantioselective version of this reaction can be developed using a chiral amine auxiliary.