A facile, catalyst- and additive-free, and scalable approach to the photochemical preparation of disulfides from organosulfenyl chlorides

Abstract

A novel, clean and efficient protocol for the preparation of disulfides has been developed through the photochemical radical homo- and cross-coupling reaction of sulfenyl chlorides under LED irradiation and without the use of any catalyst and additive. The representative photochemical homo-coupling of trichloromethyl sulfenyl chloride has been successfully conducted on kilogram-scale in a continuous flow mode. The solvent and the main byproduct can be recovered in high yields, which makes the approach be highly atom economical.

Fig. 1. Representative disulfides and their applications.

Scheme 1. Approaches for the synthesis of disulfides.

Scheme 2. Substrate scope of symmetrical disulfides. ^a Reaction conditions: substrate (5 mmol), cyclohexane (5.3 mL), LED 405 nm, 35 °C, 15 minutes. ^b Isolated yield. ^c Determined by GCMS. ^d Determined by HPLC (254 nm) area normalization method. ^e Determined by HPLC (210 nm) area normalization method.

Scheme 3. Cross coupling between trichloromethyl sulfenyl chloride (1a) and different sulfenyl chlorides.^{a,b a} Reaction conditions: substrate (1 mmol), 1a (2 mmol), cyclohexane (3.3 mL), LED 405 nm, 35 °C, 15 minutes. ^b Isolated yield base on the aryl sulfenyl chloride (R–SCl).

Scheme 4. Cross coupling between phenyl sulfenyl chloride (1b) and other aryl sulfenyl chlorides^a,b. ^a Reaction conditions: 1b (2 mmol), aryl sulfenyl chloride (1 mmol), cyclohexane (3.3 mL), LED 405 nm, 35 °C, 15 minutes. ^b Isolated yield base on R–SCl.

Scheme 5. Control experiments.

Scheme 6. A plausible mechanism.