Ligand-Enabled Nondirected and Regioselective Arylation of Internal Alkenes with Simple Arenes

Abstract

Regioselective functionalization of internal alkenes has become a highly efficient approach for preparing stereochemically defined multi-substituted olefins. Unlike traditional methods that require directing groups, activating groups, or active chemical bonds (e.g., halide, pseudo halide, organometallic reagent, etc.), there remains a strong demand for nondirected and selective functionalization of unactivated alkenes with simple coupling partners, both in academic research or industrial applications. Herein, we report the development of a pyridone-oxazoline (Pyoox) type ligand that combines the features of both pyridone and pyridine-oxazoline in assisting Pd-catalyzed olefination. This ligand enables the activation of simple (hetero) arenes and internal alkenes within a single reaction system. A nondirected and regioselective arylation from simple raw materials has been achieved, providing a straightforward route to various trisubstituted olefins in moderate to excellent yields, with excellent regio-/stereocontrol. Experimental and computational studies on mechanisms offer insight into the distinctive properties and performance of this ligand-promoted catalysis. The synthetic utility of this method is further demonstrated by the simplified synthesis and late-stage diversification of bioactive molecules.