Axially chiral arylpyrroles are a promising class of compounds with broad applications in catalysis, medicinal chemistry, and materials science. Herein, we report a copper-catalysed dynamic kinetic asymmetric (4 + 1) cyclization for the atroposelective synthesis of arylpyrroles bearing a single stereogenic axis or 1,2-diaxes from 1,3-enynes and amines. This dynamic kinetic asymmetric transformation employs a chiral Cu/Pybox complex, with air as the oxidant and DABCO serving as both a base and a proton shuttle. A key feature is the reversibility of the aza-Michael addition, which enables the dynamic formation/cleavage of distal C–N bonds. The 5-endo-dig cyclization serves as both the rate-determining and stereodetermining step, ensuring precise stereocontrol of the proximal stereocenters by the catalyst. This strategy overcomes long-standing challenges in the stereocontrol of distal C–N bond formation and enables the synthesis of atropisomeric DMAP catalysts with two stereogenic axes. DFT calculations provide insights into the mechanism of stereocontrol. Axially chiral arylpyrroles hold significant promise in catalysis, medicinal chemistry and materials science. Here, the authors report a copper-catalyzed dynamic kinetic asymmetric (4 + 1) cyclization enabling atroposelective synthesis of arylpyrroles with single stereogenic axes or 1,2-diaxes from 1,3- enynes and amines.
Zhong et al. (Wed,) studied this question.