Ni-catalyzed, enantioselective three-component radical relayed reductive coupling of alkynes: Synthesis of axially chiral styrenes

Abstract

Axially chiral styrenes are of great interest because they could serve as a class of novel chiral ligands in enantioselective synthesis. However, only recently have strategies been developed for their enantioselective preparation. Herein, we have developed a Ni-catalyzed, enantioselective, three-component radical relayed reductive coupling to rapidly construct axially chiral styrene. This three-component radical relayed reductive coupling strategy utilizes a chiral nickel/pyridine-oxazoline system to facilitate the challenging three-component, enantioselective difunctionalization of alkynes with high efficiency and excellent enantioselectivity. The mild conditions allow for broad substrate scopes as well as good functional-group toleration. We performed computational mechanistic studies to gain insights into the mechanism and origin of the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be easily transformed into 1-(1-phenylvinyl)naphthalene phosphine ( ( s )-SJTU-PHOS-1 ) with high stereoselectivities, which showed great promise as a new type of styrene ligand. • Three-component radical relayed reductive coupling to construct axial chiral styrene • Broad substrate scope with excellent enantioselectivity and regioselectivity • Axially chiral styrenes transformed into chiral ligand • Computational studies to gain insights into the chemo- and enantioselectivity Axially chiral styrene has recently attracted considerable attention from chemists because of its widespread use in biological active compounds, chiral catalysts, and ligands. In this article, we develop a radical relayed reductive coupling to construct axially chiral styrene with high efficiency and excellent enantioselectivity via highly active sp 2 center radicals. The resulting axially chiral styrenes could be easily transformed into a new type of potential styrene ligand. Mechanistically, we conducted detailed computational mechanistic studies to understand the chemo- and enantioselectivity of this reaction. We anticipate that this enantioselective three-component radical relayed reductive coupling protocol will have important implications for the construction of axially chiral styrene. Zhang and co-workers have developed a novel radical relayed reductive coupling to construct axial chiral styrene with high efficiency. A weak coordination effect, found to be crucial in nickel-catalyzed three-component cross-coupling reactions, is not required in this system. The authors performed computational studies to gain insights into the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be transformed into chiral ligand ( s )-SJTU-PHOS-1 , which showed great promise as a new styrene ligand.