Enantioselective synthesis of chiral α-azido and α-aryloxy quaternary stereogenic centers via the phase-transfer-catalyzed α-alkylation of α-bromomalonates, followed by SN2 substitution

Abstract

A new efficient synthetic method for chiral alpha-azido-alpha-alkylmalonates and alpha-aryloxy-alpha-alkylmalonates was developed. The enantioselective alpha-alkylation of diphenylmethyl tert-butyl alpha-bromomalonate under phase-transfer catalytic conditions [(S,S)-3,4,5-trifluorophenyl-NAS bromide, 50% KOH, toluene, and -40 degrees C) provided the corresponding alpha-bromo-alpha-alkylmalonates in high chemical yields (<= 98%) and high optical yields (<= 99% ee). The resulting alpha-alkylated products were converted to alpha-azido-alpha-alkylmalonates <= 97% ee) and alpha-aryloxy-alpha-alkylmalonates (<= 79%, <= 93%, ee) by S(N)2 substitution with sodium azide and aryloxides, respectively.