Enantioselective Borylcupration/Cyclization of Alkene‐Tethered Oxime Esters

Abstract

A copper‐catalyzed enantioselective synthesis of borylated 1‐pyrrolines from γ,δ‐unsaturated oxime esters is reported. Twenty‐four novel 1‐pyrroline derivatives are reported in yields ranging from 26% to 96% and enantioselectivities from 74.5:25.5 er to 99:1 er. Examples derived from α‐unsubstituted, non‐fluorinated oxime esters are reported. The hydroxyl group following oxidation of the Bpin moiety acts as a directing group in highly diastereoselective reductions of the pyrrolines to the corresponding prolinol derivatives. Additionally, the Bpin group can be retained in the products following a simplified, chromatography‐free workup procedure. DFT supports a reaction mechanism which proceeds through the formation of an (R)‐benzylic copper intermediate, followed by stereoretentive cyclization with respect to the configuration at the metalated carbon. The conclusions of the computational data are corroborated through control experiments and deuterium‐labelling studies.