Nickel/Enamine Cooperative Catalysis Enables Highly Enantioselective Allylic Alkylation of α-Branched Aldehydes
Wenqian Zhang, Hong‐Cheng Shen
Abstract
All-carbon quaternary stereocenters constitute a significant portion of natural products and bioactive compounds. Here we disclose a nickel and chiral amine cooperative catalysis to enable a highly enantioselective allylic alkylation reaction between α-branched aldehydes and a wide scope of allyl esters, allowing the all-carbon quaternary stereocenter to be accessed with excellent enantioselectivity (up to 98% ee) and structural diversity. The general synthetic applicability has been showcased by the enantioselective synthesis of key chiral building blocks to access (+)-eptazocine, (−)-aphanorphine, and other two bioactive compounds.
Topics & Concepts
Enantioselective synthesisStereocenterTsuji–Trost reactionEnamineAlkylationCatalysisChemistryAllylic rearrangementCombinatorial chemistryOrganic chemistryOrganocatalysisAsymmetric Synthesis and CatalysisAlkaloids: synthesis and pharmacologyChemical synthesis and alkaloids