Direct Asymmetric α-C Addition of Glycinate to Nitroalkenes by Pyridoxal/Nd Dual Catalysis
Shibo Si1, Qingfang Wang1, Yiming Lv1
1The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, 200234, China.
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.
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