Affiliation:
1. Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering East China University of Science and Technology 130 Meilong Road Shanghai 200237 China
Abstract
Abstractβ‐Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, the efficient asymmetric synthesis of this motif still remains a significant challenge. Herein, we disclose a cobalt‐catalyzed enantioselective reductive addition reaction of ketimine using α‐chloro carbonyl compound as a radical precursor, providing expedient access to a diverse array of enantioenriched β‐quaternary amino acid analogues. This protocol exhibits outstanding enantioselectivity and broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out the possibility of Reformatsky‐type addition and confirm the involvement of radical species in stereoselective addition process. The synthetic utility has been demonstrated through the rapid assembly of iterative amino acid units and oligopeptide, showcasing its versatile platform for late‐stage modification of drug candidates.