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

Abstract

Direct 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.