Highly enantio- stereoselective Ni-catalyzed reductive cyclization for cyclopentanes with chiral quaternary center of trisubstituted allylic siloxane

Abstract Construction of chiral quaternary carbon stereocenters is a significant challenge of asymmetric synthesis. Catalytic synthesis of these structures with trisubstituted allylic alcohols is highly important. However, most of reported methodologies required precious transition-metal catalyst. Herein we reported the first highly asymmetric stereoselective synthesis of cyclopentanes bearing chiral quaternary carbon stereocenters of trisubstituted allylic siloxanes by reductive cyclization of all carbon 1,6-alkynones with the earth-abundant Nickel catalysis Ni(cod)2 and P-chiral monophosphine ligand (S)-BIDIME. Various multi-substituted functionalized cyclopentanes were obtained in high yield (96%), excellent enantioselectivity (>99% ee) and perfect stereoselectivity (>99:1 E/Z). Thirty-two all carbon 1,6-alkynones were synthesized and successfully applied. Clarified mechanism study was investigated first time by detailed React-IR and DFT calculations to anticipate and confirm the ligand-control for the excellent enantioselectivity and stereoselectivity. Gram scale reaction and control experiments was carried out. New reaction design was proposed for further application of this methodology.