Atroposelective Synthesis of Axially Chiral 4-Aryl α-Carbolines via N-Heterocyclic Carbene Catalysis

The first catalytic asymmetric construction of axially chiral 4-aryl alpha-carboline skeletons has been accomplished through an N-heterocyclic carbene (NHC)-catalyzed atroposelective formal [3 + 3] annulation of 4-nitrophenyl 3-arylpropiolates with 2-sulfonamidoindolines. The synthetic utility of the title compounds has been demonstrated by the diverse late-stage structural modifications. Density functional theory calculations were also conducted to illuminate the key factors for controlling the origin of the enantioselectivity. This strategy not only provides an efficient pathway to access axially chiral alpha-carboline atropisomers but also offers a novel catalytic enantioselective mode for the construction of axially chiral heterobiaryls by using NHC-bound alkynyl acylazoliums.

Automated summary

A novel NHC-catalyzed method was developed to efficiently synthesize axially chiral 4-aryl alpha-carboline skeletons, which were demonstrated to be synthetically useful through late-stage structural modifications.