Copper-Catalyzed Oxygenative Skeletal Rearrangement of Tetrahydro-β-carbolines Using H2O and O2 as Oxygen Sources

Herein, we report an unprecedented skeletal rearrangement reaction of tetrahydro-beta-carbolines enabled by copper-catalyzed single-electron oxidative oxygenation, in which H2O and O-2 act as oxygen sources to generate a unique 2-hydroxyl-3-peroxide indoline intermediate. The synthetic reactivity of 2-hydroxyl-3-peroxide indoline species was demonstrated by a unique multi-step bond cleavage and formation cascade. Using a readily available copper catalyst under open-air conditions, highly important yet synthetically difficult spiro[pyrrolidone-(3,1-benzoxazine)] products were obtained in a single operation. The synthetic utility of this methodology is demonstrated by the efficient synthesis of the natural products donaxanine and chimonamidine, as well as the 3-hydroxyl-pyrroloindoline scaffold, in just one or two steps.

Automated summary

In this study, we reported an unprecedented skeletal rearrangement reaction of tetrahydro-beta-carbolines enabled by copper-catalyzed single-electron oxidative oxygenation. The reaction utilized H2O and O-2 as oxygen sources to generate a unique 2-hydroxyl-3-peroxide indoline intermediate, which underwent a multi-step bond cleavage and formation cascade. By using a readily available copper catalyst under open-air conditions, highly important spiro[pyrrolidone-(3,1-benzoxazine)] products were obtained in a single operation. This methodology demonstrated synthetic utility by efficiently synthesizing natural products and the 3-hydroxyl-pyrroloindoline scaffold in only one or two steps.