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. 2024 Dec 25;146(51):35035-35042.
doi: 10.1021/jacs.4c14421. Epub 2024 Dec 12.

Alkene Carboxy-Alkylation via CO2•

Y Dang  1 , Jimin Han  1 , Alyah F Chmiel  1 , Sara N Alektiar  1 , Myriam Mikhael  2 , Ilia A Guzei  1 , Charles S Yeung  2 , Zachary K Wickens  1
Affiliations

Alkene Carboxy-Alkylation via CO2•

Y Dang et al. J Am Chem Soc. .

Abstract

Herein, we introduce a new platform for alkene carboxy-alkylation. This reaction is designed around CO2•- addition to alkenes followed by radical polar crossover, which enables alkylation through carbanion attack on carbonyl electrophiles. We discovered that CO2•- adds to alkenes faster than it reduces carbonyl electrophiles and that this reactivity can be exploited by accessing CO2•- via hydrogen atom transfer from formate. This photocatalytic system transforms vinylarenes and carbonyl compounds into a diverse array of substituted γ-lactone products. Furthermore, indoles can be engaged through dearomative carboxy-alkylation, delivering medicinally relevant C(sp3)-rich heterocyclic scaffolds. Mechanistic studies reveal that the active photocatalyst is generated in situ through a photochemically induced reaction between the precatalyst and DMSO. Overall, we have developed a three-component alkene carboxy-alkylation reaction enabled by the use of formate as the CO2•- precursor.

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Conflict of interest statement

The authors declare no competing financial interest.

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