Highly Enantioselective Synthesis of α,α-Dialkylmalonates by Phase-Transfer Catalytic Desymmetrization

A novel enantioselective synthetic method for the construction of a quaternary carbon center from malonates via phase-transfer catalytic (PTC) alkylation has been developed. The asymmetric α-alkylation of diphenylmethyl tert-butyl α-alkylmalonates with alkylating agents under phase-transfer catalysis conditions (aq 50% KOH, toluene, 0 °C) in the presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide (8) as PTC catalyst afforded the corresponding α,α-dialkylmalonates in high chemical (up to 99%) and optical yields (up to 97% ee) which could be readily converted to versatile chiral intermediates. Notably, the direct double α-alkylations of diphenylmethyl tert-butyl malonate also provided the corresponding α,α-dialkylmalonates without loss of enantioselectivity. The synthetic potential of this method has been demonstrated by the preparation of α,α-dialkylamino acid and oxindole systems.