Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

Wen-Jun Zhou,Zhe-Hao Wang,Yuan-Xu Jiang,Tao Ju,Yiwen Li,Ke-Gong Cao,Da-Gang Yu,Guang-Mei Cao,Li-Li Liao

doi:10.1038/s41467-020-17085-9

Abstract

Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transition-metal catalysis via two electron transfer. Herein, we report a strategy of visible-light photoredox-catalyzed successive single electron transfer, realizing dearomative arylcarboxylation of indoles with CO2. This strategy avoids common side reactions in transition-metal catalysis, including ipso-carboxylation of aryl halides and β-hydride elimination. This visible-light photoredox catalysis shows high chemoselectivity, low loading of photocatalyst, mild reaction conditions (room temperature, 1 atm) and good functional group tolerance, providing great potential for the synthesis of valuable but difficultly accessible indoline-3-carboxylic acids. Mechanistic studies indicate that the benzylic radicals and anions might be generated as the key intermediates, thus providing a direction for reductive couplings with other electrophiles, including D2O and aldehyde.

Highlights

Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transitionmetal catalysis via two electron transfer
If one electrophile is tethered with the unsaturated bond, a ring could be constructed via intramolecular cyclization[7,8,9]
Many methods have been developed in this field[17,18,19,20,21,22,23,24,25], the dearomative reductive coupling of indoles with two electrophiles is still challenging due to the stability of carbon–carbon double bond within aromaticity and slow migratory insertion rate

Summary

Introduction

Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transitionmetal catalysis via two electron transfer. The transition-metal catalysis with two-electron transfer process (Fig. 1a) is powerful in tuning the reactivity and selectivity, there are still some challenges in the tandem reductive cyclization/cross-coupling.

Results

Conclusion