Hydrosulfonylation of Alkenes with Sulfonyl Chlorides under Visible Light Activation

Abstract

Sulfonyl chlorides are inexpensive reactants extensively explored for functionalization, but never considered for radical hydrosulfonylation of alkenes. Herein, we report that tris(trimethylsilyl)silane is an ideal hydrogen atom donor enabling highly effective photoredox-catalyzed hydrosulfonylation of electron-deficient alkenes with sulfonyl chlorides. To increase the generality of this transformation, polarity-reversal catalysis (PRC) was successfully implemented for alkenes bearing alkyl substituents. This late-stage functionalization method tolerates a remarkably wide range of functional groups, is operationally simple, scalable, and allows access to building blocks which are important for medicinal chemistry and drug discovery.

Keywords: alkenes; hydrosulfonylation; photochemistry; radicals; sulfonyl chlorides.

Scheme 1

A) Selected routes to functionalized sulfones. B) Photoredox‐catalyzed hydrosulfonylation of alkenes using sulfonyl chlorides (this work).

Scheme 2

Substrate scope. Reaction conditions: 1 a–o (1.25 mmol), 2 a–x (0.5 mmol), (TMS)₃SiH (1.0 mmol), fac‐Ir(ppy)₃ (0.5 mol %), MeCN (3.0 mL), blue LED irradiation (λ _max=450 nm), room temperature, 1 h. Yields of isolated products. [a] The isomers were separated by silica flash column chromatography. [b] The minor isomer was not isolated. [c] 16 h reaction time.

Scheme 3

Further applications of the hydrosulfonylation of cyclobutene derivatives. Yields of isolated products. [a] Reaction conditions: see Supporting Information. [b] The diastereoisomers were separated by silica flash column chromatography. [c] Stereochemistry was assigned by single‐crystal X‐ray diffraction analysis.

Scheme 4

Scope of other alkenes. Reaction conditions: 1 a (1.25 mmol), 7 a–j (0.5 mmol), (TMS)₃SiH (1.0 mmol), 4‐mercaptophenol (0.1 mmol), fac‐Ir(ppy)₃ (0.5 mol %), MeCN (3.0 mL), blue LED irradiation (λ _max=450 nm), room temperature, 16 h. Yields of isolated products. [a] Without thiol catalyst.

Scheme 5

A–F) Mechanistic investigations. Yields of isolated products. [a] Yield determined by ¹⁹F NMR using α,α,α‐trifluorotoluene as internal standard.

Scheme 6

A) Stern–Volmer fluorescence quenching experiments. B) Proposed mechanism for the hydrosulfonylation of alkenes.