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. 2025 Aug 1;27(30):8338-8343.
doi: 10.1021/acs.orglett.5c02611. Epub 2025 Jul 24.

Unexpected Reactivity of Nitrones: Catalytic Insertion of CS2

Marcos López-Aguilar  1 , Nicolás Ríos-Lombardía  1 , Daniel Barrena-Espés  1 , Miguel Gallegos  1 , Joaquín García-Álvarez  1 , Carmen Concellón  1 , Vicente Del Amo  1
Affiliations

Unexpected Reactivity of Nitrones: Catalytic Insertion of CS2

Marcos López-Aguilar et al. Org Lett. .

Abstract

A new reactivity mode for nitrones is reported, consisting of the chloride-catalyzed insertion of CS2 to afford thioamides. This reaction proceeds under metal-free and mild conditions, tolerates a broad family of substrates, and is robust and easily scalable, being successfully applied to the synthesis of the HIV-1 reverse transcriptase inhibitor UC-781. Mechanistic studies, supported by DFT calculations, have revealed the role of chloride anions in the activation of CS2 and its subsequent insertion into nitrones.

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Figures

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1. State of the Art for the Synthesis of Thioamides
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2. Synthesis of 4-Chloro-N-phenylbenzothioamide (3a) from CS2 and Nitrone 1a, Catalyzed by TBACl
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Reaction energy profile from Z -1b to IV (3b).
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3. Chloride-Catalyzed Synthesis of Thioamides 3a–3ah by Insertion of CS2 in Nitrones 1a-1ah
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4. Scalability and Synthetic Application of the Insertion of CS2 in Nitrones
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