Palladium-Catalyzed Modular and Enantioselective cis-Difunctionalization of 1,3-Enynes with Imines and Boronic Reagents.

Abstract

Here we report that a palladium(0) complex can mediate the unprecedented intermolecular coupling reaction of 1,3-enynes and N-sulfonylimines regio- and stereoselectively, and the resultant palladium(II) species undergo a cascade Suzuki reaction with organoboronic reagents. The substrate scope is substantial for the asymmetric three-component process, and the enantioenriched all-carbon tetra-substituted alkene derivatives are efficiently constructed in a modular and cis-difunctionalized manner. Control experiments and density functional theory (DFT) calculations support the idea that the palladium(0) acts as a π-Lewis base catalyst by chemoselectively forming η2-complexes with the alkene moiety of 1,3-enynes, thus increasing the nucleophilicity of the alkyne group based on the principle of vinylogy, to attack imines enantioselectively. The preferable formation of aza-palladacyclopentene intermediates, via a 90° single bond rotation from the resultant π-allyl complex, guarantees the formal cis-carbopalladation of alkyne group. In addition, a palladium(0)-catalyzed enantioselective reductive coupling of 1,3-enyne and imine is realized by using formic acid as hydrogen transfer reagent.