Cascade Hydrothiolation and Hydroamidation of Alkynes to Regioselectively Afford 1,2-Disubstituted Alkane Derivatives under Photocatalysis

Abstract

Herein, we report a visible-light-mediated chemo- and regio-selective installation of N and S groups onto alkynes to afford 1,2-disubstituted alkane derivatives through sequential thiol-yne click chemistry and hydroamidation of alkynes with arylthiophenols and sulfonyl azides. This transformation proceeds efficiently under mild conditions with broad substrate scope, accommodating both aromatic and aliphatic alkynes. Central to this approach is the selective activation of the aryl vinyl thioether intermediate with the excited photocatalyst via triplet-triplet energy transfer (EnT) strategy to reach its excited state, which subsequently undergoes hydrogen atom transfer (HAT) with C⁴−H bond of Hantzsch ester (HE) to result in a benzyl radical intermediate and the corresponding HE^• radical. Afterwards, these two radical species could react with sulfonyl azides, respectively, to individually yield the desired product of double hydrofunctionalization of alkynes. The afforded HE^• radical species could involve in the radical chain mechanism to furnish the product according to a combined experimental and computational study. The origins of selectivity for this reaction are also rationalized. This work establishes an alternative photocatalytic approach to tackling the challenges in selectively realizing the difunctionalization of alkynes to access 1,2-diheteroatom-substituted alkanes under mild conditions.

Keywords

Alkyne difunctionalization / Photocatalysis / Vinyl thioether / Sulfonyl azide / H-atom transfer / Radical chain mechanism / Selectivity / DFT calculation

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2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH