Alkylation of Magnesium Enamides with Alkyl Chlorides and Fluorides

Significance

This is an excellent novel approach to an old reaction - the alkylation of enolate anions. The starting enamines are easily prepared. Usually, a high regioselectivity in the deprotonation of an imine can be achieved. Even unreactive alkyl fluorides can be used as alkylating agents. The introduction of a coordinating nitrogen atom into the molecule of an enamide greatly improved its reactivity compared to the formerly known N-cyclohexyl- or N-phenyl magnesium enamides. The diethylaminoethyl moiety was found to be the optimal for the process. In the shown cases, the regioselectivity is good, although the diastereoselectivity is rather moderate. Alkyl chlorides, including secondary ones are sufficiently active as alkylating agents, and even primary fluorides can be used. The reaction is an S_N2 process, and in case of a chiral α-phenethyl chloride (>99% ee) a good enantioselectivity was achieved, which is determined rather by the stability of the alkylating reagent toward epimerization.