New axially chiral biaryl quinoline ligands specifically partnered with AgOTf enabled an enantioselective aza-Friedel–Crafts reaction

Abstract

A new class of axially chiral biaryl pyridine ligands have been rationally designed and concisely prepared in two steps by Skraup–Doebner–Miller synthesis. Their proof-of-concept application in an enantioselective aza-Friedel–Crafts reaction between 2-methylindoles and isatin N-Boc ketimines has been evaluated. Specifically partnered with AgOTf, the new ligands effectively catalysed the reaction with excellent enantioselectivities (up to 96% ee) and 71–94% yields, and a series of multifunctional chiral 3-indolyl 3-amino-oxindoles were successfully obtained. Compared with other noble metals and chiral ligands, this Ag(I)-B1 partner is highly stable, cost-effective, facile and easily available. This work has successfully demonstrated the good performance of a new kind of axially biaryl quinoline ligands and is the first example of a silver-catalysed enantioselective aza-Friedel–Crafts reaction between 2-methylindoles and isatin N-Boc ketimines, and has thus enriched the application of silver salts in asymmetric catalysis.