Highly Enantioselective Conjugate Addition of Nitroalkanes to Alkylidenemalonates Using Efficient Phase-Transfer Catalysis of N-Spiro Chiral Ammonium Bromides

Abstract
Highly enantioselective conjugate addition of nitroalkanes to alkylidenemalonates has been accomplished for the first time by the utilization of efficient phase-transfer catalysis of N-spiro C2-symmetric chiral quaternary ammonium bromide 1. For instance, simple mixing of nitropropane (2, R 1 = Et), diisopropyl benzylidienemalonate (3, R 2 = Ph), Cs2CO3 (1 equiv), and (S,S)-1 (1 mol %) in toluene at 0 °C for 2.5 h gave rise to the desired conjugate addition product 4 (R1 = Et, R2 = Ph) quantitatively (anti/syn = 86:14) with 97% ee (anti isomer). The applicability of this procedure has been demonstrated with other representative alkylidenemalonates and nitroalkanes. Since 4 can be readily transformed into the corresponding γ-amino acid hydrochloride 5 without loss of diastereo- and enantioselectivity, the present method provides a new and practical access to various optically active γ-amino acid derivatives.