An Iodide-Mediated Transition-Metal-Free Strategy towards Unsymmetrical Diaryl Sulfides via Arylhydrazines and Thiols

Abstract

A mild, scalable iodine-mediated oxidative cross-coupling reaction of arylhydrazines and thiols for construction of thioethers (sulfides) in the absence of any transition metals or photocatalysts is disclosed. A variety of unsymmetrical diaryl sulfides with broad substrate scope both on thiols and hydrazines were synthesized in high yields in water at room temperature. Furthermore, to demonstrate the utility of the protocol, the above C–S bond formation was applied in the synthesis of the key structure of vortioxetine as an antidepressant drug. The gram-scale outcome also added to the potential utility of this protocol.

A review on the latest progress of C‐S cross‐coupling in diaryl sulfide synthesis: Update from 2012 to 2021

“…They utilized TBHP as an oxidant and KI as an additive in this reaction (Scheme 46). [70] Joussef et al reported the synthesis of diaryl sulfides through C (sp 2 )-H bond sulfenylation of (hetero)arenes using a KIO 3 /ethylene glycol catalytic system. Several of the sulfurated (hetero)arenes revealed a high percent of AChE inhibition, revealing their potential anti-Alzheimer activity.…”

Recent Advances in the Synthesis of Sulfides, Sulfoxides and Sulfones via C-S Bond Construction from Non-Halide Substrates

“…It is interesting that pentafluorobenzoic acid was dithiolated under the optimal condition. In 2019, the Jafarpour group reported a simple procedure for the synthesis of unsymmetrical diaryl sulfides from arylhydrazines and aryl thiols (Scheme 25) [45]. The reaction proceeded at room temperature in the presence of TBHP, KI, and Cs 2 CO 3 in water, providing the corresponding sulfides in good yields.…”

Environmentally Benign Large-Scale Synthesis of a Precursor to Vortioxetine

“…Treatment of the benzyne generated in situ from 2-(trimethylsilyl)phenyl triflate (using excess CsF) with N-Boc-protected 1-[(2,4-dimethylphenyl)thio]piperazine in DME as solvent, followed by deprotection led to the formation of vortioxetine. In 2020, Jafarpour et al 7 reported an iodine-mediated oxidative cross-coupling reaction of arylhydrazines and thiols for construction of thioethers in the absence of any transition metals or photocatalysts and this method was applied in the synthesis of the key structure of vortioxetine.…”