Stereodivergent Synthesis of Enantioenriched 2-Pyrrolidones via Diastereoselective Hydrogenation of α,β-Unsaturated γ-Lactams

Abstract

Synthesis of optically enriched racetam analogues was achieved via highly remote diastereocontrolled and enantiocontrolled Pd/C-catalyzed hydrogenation of α,β-unsaturated γ-lactams. Various mono-and disubstituted 2-pyrrolidones were obtained in excellent yields and stereoselectivities, and a concise and large-scale synthesis of brivaracetam was developed from inexpensive L-2-aminobutyric acid. Surprisingly, stereodivergent hydrogenation was observed by modifying remote functionalized stereocenters and additives, which would provide alternative stereochemical options of chiral racetams synthesis.