Single-Flask Multicomponent Palladium-Catalyzed α,γ-Coupling of Ketone Enolates: Facile Preparation of Complex Carbon Scaffolds

Abstract

A three-component palladium-catalyzed reaction sequence has been developed in which γ-substituted α,β-unsaturated products are obtained in a single flask by an α-alkenylation with either a subsequent γ-alkenylation or γ-arylation of a ketone enolate. Coupling of a variety of electronically and structurally different components was achieved in the presence of a Pd/Q-Phos catalyst (2mol %), usually at 22 C with yields of up to 85 %. Most importantly, access to these products is obtained in one simple operation in place of employing multiple reactions. Building bridges: The title reaction was developed for the construction of γ-substituted α,β-unsaturated ketones under mild reaction conditions. High levels of regioselectivity and control of incorporation of reaction components are exhibited, thus producing complex scaffolds in a single-flask procedure. dba=dibenzylideneacetone, THF=tetrahydrofuran, Q-Phos=1-di-tert-butylphosphino-1′,2′,3′,4′,5′-pentaphenylferrocene.