Thioethers, often found in pharmaceuticals and natural compounds, typically involve metal cross-coupling reactions, high temperatures, and the use of disagreeable thiols for their synthesis. Here we present a straightforward, thiol-free organocatalytic protocol that uses mild conditions to stitch together inexpensive alcohols and aryl chlorides, yielding a diverse array of aryl alkyl thioethers. Central to this approach was the discovery that tetramethylthiourea can serve as a simple sulfur source upon intercepting photochemically generated aryl radicals. To form radicals, we used a readily available indole thiolate organocatalyst that, when excited with 405 nm light, gained a strongly reducing power, enabling the activation of typically unreactive aryl chlorides via single-electron transfer. Radical trapping by the thiourea, followed by an alcohol attack via a polar path, resulted in the formation of thioether products.

Photochemical Organocatalytic Synthesis of Thioethers from Aryl Chlorides and Alcohols / Wu, Shuo; Wong, Thomas Hin-Fung; Righi, Paolo; Melchiorre, Paolo. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 146:5(2024), pp. 2907-2912. [10.1021/jacs.3c13900]

Photochemical Organocatalytic Synthesis of Thioethers from Aryl Chlorides and Alcohols

Righi, Paolo
Penultimo
Supervision
;
Melchiorre, Paolo
Ultimo
Funding Acquisition
2024

Abstract

Thioethers, often found in pharmaceuticals and natural compounds, typically involve metal cross-coupling reactions, high temperatures, and the use of disagreeable thiols for their synthesis. Here we present a straightforward, thiol-free organocatalytic protocol that uses mild conditions to stitch together inexpensive alcohols and aryl chlorides, yielding a diverse array of aryl alkyl thioethers. Central to this approach was the discovery that tetramethylthiourea can serve as a simple sulfur source upon intercepting photochemically generated aryl radicals. To form radicals, we used a readily available indole thiolate organocatalyst that, when excited with 405 nm light, gained a strongly reducing power, enabling the activation of typically unreactive aryl chlorides via single-electron transfer. Radical trapping by the thiourea, followed by an alcohol attack via a polar path, resulted in the formation of thioether products.
2024
Photochemical Organocatalytic Synthesis of Thioethers from Aryl Chlorides and Alcohols / Wu, Shuo; Wong, Thomas Hin-Fung; Righi, Paolo; Melchiorre, Paolo. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 146:5(2024), pp. 2907-2912. [10.1021/jacs.3c13900]
Wu, Shuo; Wong, Thomas Hin-Fung; Righi, Paolo; Melchiorre, Paolo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/956233
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