Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins

Abstract

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.