Visible-Light-Induced Organophotocatalytic Difunctionallization: Open-Air Hydroxysulfurization of Aryl Alkenes with Aryl Thiols

Abstract

Herein, we report a regioselective visible-light-induced organophotoredox catalytic difunctionalization method to prepare β-hydroxysulfides using aryl alkenes and aryl thiols as substrates. The reaction provides a wide substrate scope of aryl alkenes (from simple styrene to complex bioactive compounds) and aryl thiols (from diverse heteroaromatic thiols to nonhetero­aromatic thiols) (total 45 examples, up to 88% yield). Based on the combined experimental and computational studies, we demonstrate that in situ generated hydroperoxyl radicals from O2 in air react with benzylic radicals, which restrains the reaction between benzylic radicals and the acidic form of thiols in a classical thiol–ene radical reaction. We show that difunctionalization is possible due to the choice of bases, diluted substrate concentrations, increment in catalyst loading, and selection of suitable aryl thiols under aerobic conditions. Considering the biological importance of heteroaromatic thiols and the lack of methods to install them, our approach offers a platform to derive various β-hydroxysulfides that contain aromatic elements.

Visible light-induced organophotoredox-catalyzed difunctionalization of alkenes and alkynes

“…In 2022, Park et al 61 reported a visible light-induced organophotocatalytic hydroxysulfenylation of alkenes 43a using heteroaromatic or non-heteroaromatic thiols ( 43b ) to synthesize a bunch of β-hydroxysulfides with up to 74% yield within 24 h (Scheme 43). However, the difunctionalization required 10 mol% 9-mesityl2,7-dimethyl-10-phenylacridinium tetrafluoroborate (C) as the organophotocatalyst and K 2 CO 3 as the base in acetone solvent under the irradiation of blue LED and ambient air at room temperature.…”

Recent Advances in Photoredox-Catalyzed Difunctionalization of Alkenes

“…Mechanistic studies have demonstrated that the photocatalyst-promoted radical formation from H donors was the key process in this transformation. In 2022, Park and co-workers [87] developed a -Mes-2,7-diMe-AcrPhBF4-catalyzed difunctionalization of aryl alkenes to prepare various β-hydroxysulfides. The reaction is applicable in converting a wide scope of substrates to the corresponding β-hydroxysulfides products (45 examples, 25-88% yield), including various aryl alkenes (from simple styrene to complex bioactive compounds) and structurally diverse aryl thiols (from diverse heteroaromatic thiols to nonheteroaromatic thiols).…”

Asymmetric Radical-Type 1,2-Alkoxy-Sulfenylation of Benzoxazole-2-Thiols to Vinylarenes Catalyzed by Chiral Vanadyl Complexes

“…25 In particular, Prof. Yoyan Park and co-workers have demonstrated photocatalytic 1,2-hydroxy-sulfenylation by Nphenyl-acridinium tetrafluoroborates as photocatalysts in acetone. 26 During this study, unique resonance electronwithdrawing (REW) heteroarene-thiols, including 2-mercapto-tetrazoles, thia-diazoles, and (benzo)thiazoles/oxazoles, were utilized. Notably, this system led to unique racemic products that were so far not accessible through the reactions of olefins with thiosulfonium ions, presumably due to their intrinsic instabilities exerted by the REW heteroaryl moieties.…”

“…Analogous β-hydroxy arenethiols can be synthesized by reductive workup of the corresponding β-peroxy-sulfides (by PPh 3 or 3° amines) from direct radical type addition of arenethiols to alkenes followed by oxygen trapping under thermal, photolytic, − electrolytic, or catalytic treatment of t -butyl hydroperoxide (TBHP) (Scheme A) . In particular, Prof. Yoyan Park and co-workers have demonstrated photocatalytic 1,2-hydroxy-sulfenylation by N -phenyl-acridinium tetrafluoroborates as photocatalysts in acetone . During this study, unique resonance electron-withdrawing (REW) heteroarene-thiols, including 2-mercapto-tetrazoles, thia-diazoles, and (benzo)­thiazoles/oxazoles, were utilized.…”