Asymmetric Bimetallic Catalysis Enabled Alkenyl Z/E Mutual Isomerization

Abstract

Olefins are fundamental functional groups present in numerous molecules, and the geometrical configuration of the C═C bonds often plays a critical role in determining the properties of these compounds. Alkenyl geometrical isomerization is, in principle, one of the most efficient approaches for accessing stereodefined olefins. While some progress has been made in achieving unidirectional Z → E or E → Z conversion via olefin geometrical isomerization, there remains a strong demand for controllable, bidirectional geometrical isomerization of C═C bonds. Herein, we present a method for Z/E mutual isomerization of alkenyl groups by using a Pd/Cu catalytic system. This process involves Pd-mediated π–σ–π interconversion followed by selective trapping of the π-allyl-Pd intermediates with N-metalated azomethine ylides generated by a chiral Cu-catalyst. The reaction enables the synthesis of chiral non-natural amino acid derivatives bearing Z- and E-alkenyl groups in an enantio- and Z/E-divergent manner, achieving yields of up to 92%, > 20:1 Z/E or E/Z, and >99% ee. Furthermore, the reaction is scalable to gram quantities, and the resulting products can be transformed into valuable molecules adorned with Z- or E-alkenyl groups. Computational studies show that the bimetallic catalytic system better distinguishes among eight stereoisomers of π-allyl-Pd intermediates than the monometallic system, which results in exceptional Z/E-selectivity of the products. This method offers a robust protocol for synthesizing Z- or E-trisubstituted olefins bearing a chiral motif utilizing a readily available Z/E-mixture of substrates.