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. 2023 Feb 8;145(5):2773-2778.
doi: 10.1021/jacs.2c12699. Epub 2023 Jan 31.

Polarity Transduction Enables the Formal Electronically Mismatched Radical Addition to Alkenes

Subhasis Paul  1   2 , Dario Filippini  1   2 , Mattia Silvi  1   2
Affiliations

Polarity Transduction Enables the Formal Electronically Mismatched Radical Addition to Alkenes

Subhasis Paul et al. J Am Chem Soc. .

Abstract

The formation of carbon-carbon bonds via the intermolecular addition of alkyl radicals to alkenes is a cornerstone of organic chemistry and plays a central role in synthesis. However, unless specific electrophilic radicals are involved, polarity matching requirements restrict the alkene component to be electron deficient. This limits the scope of a fundamentally important carbon-carbon bond forming process that could otherwise be more universally applied. Herein, we introduce a polarity transduction strategy that formally overcomes this electronic limitation. Vinyl sulfonium ions are demonstrated to react with carbon-centered radicals, giving adducts that undergo in situ or sequential nucleophilic displacement to provide products that would be inaccessible via traditional methods. The broad generality of this strategy is demonstrated through the derivatization of unmodified complex bioactive molecules.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a) Polarity Matching Requirements in Radical Addition to Alkenes; (b) Polarity Transduction Strategy to Access Polarity-Mismatched Products; (c) Design of the Photocatalytic System
Scheme 2
Scheme 2. Reaction Scope
Preformed captopril dianion was used as limiting reagent (see Supporting Information for full details). After nucleophile addition, the reaction was sealed and heated to 120 °C. Diphenyl vinyl sulfonium triflate 9a, KOtBu, catalytic 3CzClIPN were used and irradiation was performed at 0 °C. Reaction stoichiometry: 10a (2.0 equiv), 9c (2.2 equiv), 4CzIPN (10 mol %), and nucleophile (1.0 equiv). 0.1 mmol scale. After nucleophile addition, the reaction was sealed and heated to 100 °C. Reactions were performed in a 0.2 mmol scale, using 10 (1 equiv), 9c (1.5 equiv), 4CzIPN (5 mol %), and nucleophile (typically 2.5 equiv), in CH3CN unless otherwise stated; see Supporting Information for full experimental details.Cz: carbazolyl.
Scheme 3
Scheme 3. In Situ Generation of the Vinyl Sulfonium
Reaction performed in a 0.2 mmol scale, using 10a (1 equiv), 13 (1.5 equiv), 4CzIPN (5 mol %) and mercaptoethanol (2.5 equiv); see Supporting Information for details.
See this image and copyright information in PMC

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