Ru‐Catalyzed Direct Asymmetric Reductive Amination of Bio‐Based Levulinic Acid and Ester for the Synthesis of Chiral Pyrrolidinone

Abstract

AbstractDirect asymmetric reductive amination of bio‐based levulinic acid (LA) to the enantioenriched 5‐methylpyrrolidinone is achieved by using a readily available chiral Ru/bisphosphine catalyst with excellent enantioselectivity (up to 96 % ee) and high isolated yield (up to 89 %). Methyl levulinate (ML), a byproduct from the industrial production of 2,5‐furandicarboxylic acid (FDCA), can be used instead of LA with similar reactivity and selectivity. Mass spectrometry and isotope labelling studies indicate that the chiral lactam is formed via imine‐enamine tautomerization/cyclization followed by asymmetric hydrogenation of the cyclic enamide.