Nickel/Enamine Cooperative Catalysis Enables Highly Enantioselective Allylic Alkylation of α-Branched Aldehydes

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 alpha-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.

Automated summary

All-carbon quaternary stereocenters are important components of natural products and bioactive compounds, and a nickel and chiral amine cooperative catalysis has been disclosed to enable highly enantioselective allylic alkylation reactions. This method allows for the synthesis of diverse compounds with excellent enantioselectivity, and has been demonstrated in the synthesis of key chiral building blocks for bioactive compounds such as (+)-eptazocine and (-)-aphanorphine.