Enantioselective palladium/copper-catalyzed C-C σ-bond activation synergized with Sonogashira-type C(sp3)-C(sp) cross-coupling alkynylation

Abstract

The Sonogashira-type cross-coupling reaction is one of the most significant alkynylation transformations in organic chemistry. However, highly enantioselective alkynylation via the Sonogashira-type cross-coupling reaction is rather limited, mainly due to the difficulties in matching the stereoselective induction of chiral ligands with the combinational behavior of Pd/Cu-based bimetallic catalysts. We herein report novel enantioselective palladium/copper-catalyzed alkyl alkynylation of cyclobutanones with terminal alkynes via tandem C-C bond activation/Sonogashira-type cross coupling reaction, in which a novel chiral TADDOL-derived phosphoramidite ligand bearing fluorine and silicon-based bulky groups simplified as TFSi-Phos is found to be an efficient ligand for both C(sp2)-C(sp3) bond cleavage and new C(sp3)-C(sp) bond formation. A wide range of chiral alkynylated indanones bearing an all-carbon quaternary stereocenter are obtained efficiently with up to 97.5:2.5 er.