Photoredox/HAT-Catalyzed Dearomative Nucleophilic Addition of the CO2 Radical Anion to (Hetero)Aromatics

The radical anion of CO2 (CO2 center dot-) is a strongly nucleophilic radical species with rapidly emerging applications in contemporary organic chemistry. This radical species exhibits high reactivity in single-electron reduction reactions due to the concomitant release of stable CO2, or Giese-type reactions, especially for electron-deficient alkenes and styrene derivatives. In contrast to previous reports, we herein disclose the development of a robust method for the introduction of CO2 center dot-, which can be generated from cesium formate under photoredox/hydrogen atom transfer (HAT) catalysis, into stable heteroaromatics such as benzofuran, benzothiophene, and indole derivatives to afford synthetically useful alpha-oxy, alpha-thio, and alpha-amino acid derivatives in moderate to high yield. In addition, when using electron-deficient naphthalene derivatives, both single-electron reduction and Giese-type nucleophilic addition occur simultaneously to produce carboxylated tetrahydronaphthalene derivatives in good yield. Moreover, one of the tetrahydronaphthalenes that bear a cyano group was transformed into the corresponding gamma-butyrolactam via reduction of the cyano functionality through hydrogenation followed by cyclization. To the best of our knowledge, these dearomative carboxylation reactions with metal formates under photoredox/HAT conditions are unprecedented, thus providing a synthetic option for the introduction of a C1 source into stable (hetero)aromatics.

Automated summary

The radical anion of CO2 is a highly nucleophilic radical species with many potential applications in organic chemistry. In this study, a robust method for introducing CO2 center dot- into stable heteroaromatics was developed. The resulting reactions produced synthetically useful alpha-oxy, alpha-thio, and alpha-amino acid derivatives, as well as carboxylated tetrahydronaphthalene derivatives. These dearomative carboxylation reactions are unprecedented and provide a synthetic option for introducing a C1 source into stable (hetero)aromatics.