Thiuram Disulfide Mediated Copper-Catalyzed C–S Cross-Coupling: Synthesis of S-Thiocarbamate Compounds

Abstract

Thiuram disulfides undergo a Cu(I)-catalyzed C–S cross-coupling with aryl iodides through Cu(OAc)₂·H₂O-assisted desulfurization to produce the S-thiocarbamate ester compounds efficiently. Various aryl iodides containing diverse substituents underwent a smooth reaction with a series of cyclic and acyclic secondary amine-based thiuram disulfides under an open-air atmosphere. A probable mechanistic pathway has been suggested based on control experiments and reports from the literature.

Key words

thiuram disulfides - thiocarbamates - C–S cross-coupling - copper catalysis - dithiocarbamates

• References and Notes

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• 11 Thiuram Disulfides (2);⁶ General Procedure The appropriate secondary amine (20 mmol, 2 equiv) was added to a 50 mL round-bottomed flask equipped with a stirrer bar and containing DMF (30 mL). The mixture was stirred for 5 min, then CS₂ (10 mmol, 1 equiv) was added under ice-cold conditions. CBr₄ (10 mmol, 1 equiv) was then added, and the resulting solution was stirred for 1.5 h at r.t. The solution was then poured into ice-cold H₂O (100 mL) and the resulting mixture was extracted with EtOAc. The extracts were dried (Na₂SO₄) and then concentrated in a rotatory evaporator to give the white crystalline thiuram disulfide.
• 12 S-Phenyl Piperidine-1-carbothioate (3b) PhI (1a; 51 mg, 0.25 mmol, 1 equiv), Cu(OAc)₂·H₂O (200 mg, 1 mmol, 4 equiv), CuI (10 mg, 20 mol%), K₂CO₃ (276 mg, 2 mmol, 8 equiv), and a 5–6 M solution of THBP in decane (0.5 mmol, 2 equiv) were added to a solution of thiuram disulfide 2a (160 mg, 0.5 mmol, 2 equiv) in DMSO (2 mL), and the mixture was stirred for 8–10 h at 110 °C in an oil bath under open air. The mixture was then extracted with EtOAc and the extracts were dried (Na₂SO₄). The product was isolated by column chromatography [silica gel, hexane–EtOAc (95:5)] to give a white solid; yield: 42 mg (76%). ¹H NMR (300 MHz, CDCl₃): δ = 7.53–7.47 (m, 2 H), 7.41–7.35 (m, 3 H), 3.56–3.52 (m, 4 H), 1.70–1.60 (m, 6 H). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 165.5, 135.9, 129.1, 128.9, 128.8, 45.4, 25.8, 24.5.