A Direct Preparation of Functionalized Aryl and Heteroaryl Disulfides from Functionalized Zinc Organometallics by Using Sulfur Monochloride (S₂Cl₂)

Abstract

A range of functionalized aryl and heteroaryl disulfides has been prepared from zinc organometallics by using sulfur monochloride (S₂Cl₂). The zinc reagents were obtained by transmetalation from magnesium or lithium reagents with ZnBr₂.

zinc organometallic reagents - sulfur monochloride - aryl disulfides - heteroaryl disulfides - functionalized arylmagnesium halides

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12

Typical Procedure. Preparation of the Functionalized Indolyl Disulfide 2k.
A dry and nitrogen flushed 25 mL Schlenk flask, equipped with a rubber septum and a magnetic stirring bar, was charged with dry THF (5.0 mL) and 3-iodo-1-(phenyl-methyl)-1H-indole-2-carboxylic acid ethyl ester (403 mg, 0.99 mmol). The solution was cooled to -20 °C and
i-PrMgCl (1.12 mL, 1.00 mmol, 0.9 M in THF) was added slowly. The reaction mixture was stirred at that temperature until the I/Mg-exchange was complete (0.5 h, checked by GC), cooled to -40 °C, ZnBr₂ (0.64 mL, 1.09 mmol, 1.7 M in THF) was added and the white suspension was stirred for 30 min at that temperature. The heterogeneous mixture was cooled to -80 °C and S₂Cl₂ (67 mg, 0.50 mmol) was added dropwise. After 10 min the reaction mixture was quenched with sat. NH₄Cl solution (50 mL), extracted with Et₂O (3 × 50 mL), the combined organic layers were washed with brine (50 mL), dried over MgSO₄ and concentrated in vacuo. Flash chromatographic purification on silica gel (pentane-Et₂O = 3:1) furnished 2k as a light yellow solid (193 mg, 0.31 mmol, 62%, mp >240 °C decomposition).