Asymmetric Alkylation of Malonic Diester Under Phase-Transfer Conditions

An enantioselective phase-transfer catalytic alkylation of α-monosubstituted malonic diester has been developed. The alkylation of α-monosubstituted tert-butyl methyl malonate in the presence of N-(9-anthracenylmethyl)cinchoninium chloride afforded α,α-disubstituted products in high yields and with high enantioselectivities. Moreover, a successful gram-scale (10 mmol) experiment using the cinchona catalyst indicates the potential for practical applications of this methodology. To demonstrate the utility of this method, product with a quaternary chiral carbon was converted to both (R)- and (S)-α,α-dialkylated amino acids through alternative chemoselective transformation of the two ester groups.