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.