Organocatalytic intramolecular (4 + 2) annulation of enals with ynamides: atroposelective synthesis of axially chiral 7-aryl indolines

Abstract

Catalytic enantioselective transformation of alkynes has become a powerful tool for the synthesis of axially chiral molecules. Most of these atroposelective reactions of alkynes rely on transition-metal catalysis, and the organocatalytic approaches are largely limited to special alkynes which act as the precursors of Michael acceptors. Herein, we disclose an organocatalytic atroposelective intramolecular (4 + 2) annulation of enals with ynamides. This method allows the efficient and highly atom-economical preparation of various axially chiral 7-aryl indolines in generally moderate to good yields with good to excellent enantioselectivities. Computational studies were carried out to elucidate the origins of regioselectivity and enantioselectivity. Furthermore, a chiral phosphine ligand derived from the synthesized axially chiral 7-aryl indoline was proven to be potentially applicable to asymmetric catalysis.