Direct Asymmetric α‐C Addition of Glycinate to Nitroalkenes by Pyridoxal/Nd Dual Catalysis

Abstract

Direct enantioselective α‐C Michael addition of NH2‐unprotected glycinate to nitroalkenes is a significant organic transformation, which may provide a highly efficient strategy to make bioactive chiral γ‐nitro‐α‐amino acid esters. However, it is extremely challenging to achieve this reaction due to the interference of the reactive NH2 group, potential [3+2] cycloaddition side reaction and complicated stereoselective control. Carbonyl catalysis is an effective strategy to activate glycinate by forming an imine to facilitate the conjugate addition. With a pyridoxal/Nd dual catalytic system, direct asymmetric α‐C conjugate addition of glycinate to nitroalkenes has been successfully developed for the first time, producing a broad range of chiral γ‐nitro‐α‐amino acid esters in high yields with excellent stereoselectivities (up to 98% yield, >20:1 dr, 98% ee). The products can be easily converted into various biologically significant chiral molecules maintaining the same enantiopurity.