Visible-light photoredox-catalyzed umpolung carboxylation of carbonyl compounds with CO2

Guang-Mei Cao,Jason J Chruma,Si-Shun Yan,Li Gong,Xin-Long Hu,Lei Song,Da-Gang Yu,Li-Li Liao

doi:10.1038/s41467-021-23447-8

Guang-Mei Cao, Jason J Chruma + Show 6 more

Open Access

https://doi.org/10.1038/s41467-021-23447-8

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Abstract

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds with CO2 remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2 by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO2 (to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.

Highlights

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds
In addition to direct single electron transfer (SET) reduction of carbonyls[4], the photocatalytic proton-coupled electron transfer (PCET)[5] approach represents a powerful tool for SET reduction of unactivated carbonyls to generate ketyl radicals (Fig. 1a), which could undergo diverse transformations, including ketyl-olefin/alkyne coupling[6,7,8,9,10], ketylketyl homocoupling[11], and other couplings[12,13,14,15,16]
Significant progress has been achieved in recent decades to generate α-hydroxycarboxylic acids with CO218–20,40–43, most of these methods suffer from the utilization of stoichiometric amounts of metal reductants, low functional group tolerance, limited substrate scope, and/or competitive side reactions, especially the pinacol coupling and reduction, hampering industrial application

Summary

Introduction

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. We report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2 by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. Significant progress has been achieved in recent decades to generate α-hydroxycarboxylic acids with CO218–20,40–43, most of these methods suffer from the utilization of stoichiometric amounts of metal reductants, low functional group tolerance, limited substrate scope, and/or competitive side reactions, especially the pinacol coupling and reduction, hampering industrial application. We show a general and practical reductive carboxylation of carbonyl compounds, such as alkyl aryl ketones, diaryl ketones, α-ketoamides, α-ketoesters, and aryl aldehydes, with CO2 to give valuable αhydroxycarboxylic acids (Fig. 1c)

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