Copper-Catalyzed Cyclization/Dimerization of Tryptamines with O₂/Air as the Sole Oxidant: Direct Access to Complex Bispyrrolidino[2,3-<i>b</i>]indoline

Abstract

The first transition metal catalytic one-step synthesis of the 3a, 3a'-bispyrrolidino [2,3-<i>b</i>] indoline scaffold via tandem cyclization/dimerization of tryptamines has been realized with the environmentally friendly O₂/air as the sole oxidant. Different from the traditional direct oxidation of indole "N-H" group by excess amount of metal salts, a copper-catalyzed oxidative cyclization reaction is developed for the formation of the radical pyrrolidinoindoline intermediate in the current strategy. The robustness and practicality of this methodology is demonstrated by the step-economic, divergent total synthesis of natural products (±)-folicanthine and <i>meso</i>-folicanthine.