Stereodivergent Synthesis of Allylic All-Carbon Quaternary Centers by Bimetallic Iridium/Magnesium-Catalyzed Allylic Alkylation

Stereodivergent synthesis of the structural motif bearing vicinal stereocenters is highly important for complete evaluation of their physiological activities. Branched- and enantioselective allylic alkylation using synergistic dual catalysis has emerged as a powerful strategy to access multiple molecular stereoisomers with precise control of the absolute and relative configuration. Despite impressive progress in this field, the stereodivergent allylic alkylation by employing trisubstituted allylic electrophiles to construct allylic quaternary stereocenters remains an unsolved challenge. Herein, we report a combination of iridium and magnesium catalysis for stereodivergent allylic alkylation of α-benzothiazyl acetamide by using challenging trisubstituted allylic carbonates. Such a stereodivergent process gives a range of all four stereoisomers of α-allylated acetamide products containing congested allylic quaternary and vicinal tertiary stereocenters in good yields with excellent diastereo- and enantioselectivities. The synthetic utility of this methodology is demonstrated through the preparation of key intermediates for a number of natural products. Particularly, stereodivergent synthesis of an analgesic drug derivative Me-tapentadol has been achieved, exhibiting significantly enhanced μ-opioid receptor agonistic activity compared to its parent compound.