MEMORY OF CHIRALITY

The chiral ketone 1 was treated with potassium hydride and a series of alkyl halides in the presence of 18-crown-6 to furnish chiral alkylated ketones 2 in 48 approximately 73% ee without any external chiral source. These findings contravene the accepted view that chirality at the alpha-carbon to carbonyl groups is lost in the corresponding enolates because the enolates themselves are achiral. To explain this phenomenon, we propose the novel concept that chirality at the alpha-carbon to the carbonyl group is memorized as dynamic axial chirality with respect to the C1-C2 bond in the intermediate enolate, and is then regenerated as central chirality in the reaction products (memory of chirality). This mechanism was supported by trapping the enolate as a methyl enol ether 11 of 65% ee. The present concept was successfully applied to the development of the asymmetric alpha-alkylation reactions of alpha-amino acids. Thus, phenylalanine derivative 22 was found to undergo asymmetric alpha-alkylation in up to 88% ee when treated with lithium 2,2,6,6-tetramethylpiperidide followed by alkyl halides.