Palladium-catalysed Tsuji–Trost-type vinyl epoxide cross-coupling with umpolung hydrazones

Abstract

Selective functionalisation of synthetically useful vinyl epoxides via carbon–carbon (C–C) bond formation has been a major challenge for many years due to its unique inherent chemical reactivity. Non-stabilised carbanions in the form of organometallic reagents have been shown to be robust and versatile reagents in C–C bond formation; however, they are employed in superstoichiometric quantities, require the protection of active functional groups, and generate copious amounts of metallic waste. Therefore, the development of mild carbanion sources as simple alternatives is highly desired. In this work, we report a highly chemo- and regioselective palladium-catalysed vinyl epoxide cross-coupling utilising hydrazones as organometallic equivalents (HOME). Hydrazones, generated from carbonyl-containing renewable feedstocks, enable a more sustainable reaction, and provide an alternative to highly reactive and sensitive unstabilized organometallic reagents. A broad substrate scope, with high functional group tolerance, is demonstrated along with the late-stage functionalisation of natural product derivatives.