Fe-Mediated S–S Bond Cleavage and Its Application in the Synthesis of α-Arylthio Carbonyl Compounds

Abstract

In the presence of iron dust, diaryl disulfides react with α-bromo carbonyl compounds to obtain α-arylthio carbonyl compounds in good yield at 90 o C under N 2 atmosphere, using commercial DMF as solvent. The possible reaction mechanism is that the disulfide is reduced by iron dust to give ArSFeSAr, and then reacted with α-bromo carbonyl compounds to give product α-arylthio carbonyl compounds and FeBr 2 .Organic sulfur compounds have become of increasing importance in organic synthesis.As important difunctional compounds and attractive synthetic intermediates in organic synthesis, α-arylthio carbonyl compounds have received considerable attentions. [1][2][3][4] The general method for their preparation is via the reaction of thiols with α-halo carbonyl compounds, but this requires the use of the toxic and odorous thiols as starting Downloaded by [New York University] at 16:14 31 May 2015 2materials. [5][6][7][8][9] It is well known that diaryl disulfides, which are air-stable, low-toxicity and free of smell, have been in great demand as intermediates to synthesis of organic sulfur compounds. Many approaches for reducing disulfides have been reported.Previously, some of the more common reducing agents such as NaBH 4 , [10] LiAlH 4 , [11] K(i-PrO) 3 BH, [12,13] LiAlH(NR 2 ) 3 , [14] Li(t-BuO) 3 AlH, [15] PPh 3 , [16] P(n-Bu) 3 , [17,18] have been used to reductively cleave the S-S bond. Recently, some metals such as In, [19,20] Sn, [21] La, [22] or some metal halides such as InI, [23] or a combination of samarium and a metal halide such as Sm/NiCl 2 , [24] and Sm/CoCl 2 , [25] were reported to cleave S-S bonds efficiently. Iron (Fe) is an abundant, inexpensive, and nontoxic metal in nature. It has been widely used in organic synthesis as a high-efficient reducing agent. [26][27][28][29][30][31][32] So far, Fe-mediated cleavage of S-S bond has been not reported. In this paper we report the results and its application in synthesis of α-arylthio carbonyl compounds.Firstly, the reaction of diphenyl disulfide (0.5 mmol) and α-bromo ethyl ester (1.0 mmol) was used as model, and the results showed that no product can be obtained in commercial tetrahydrofuran (THF) in the presence of iron dust (3.0 mmol) at room temperature under N 2 atmosphere for 12 h. When the temperature was increased to 60 o C, the reaction occured with 16% yield. To obtain the best experimental conditions, the effects of solvents and temperature as well as time on the reaction were systematically investigated (Table 1). It can be seen that the reaction can hardly occur in dichloromethane at room temperature (Table 1, entry 3), with toluene or 1,4-Dioxane showing very low efficiency Downloaded by [New York University] at 16:14 31 May 2015 3 (Table 1, entry 4-5). When commercial DMF was used as solvent, we afforded compound 3a in the yield of 67% at 70 o C for 12 h (Table 1, entry 6). Furthermore, we also investigated the effect of time and temperature on the reaction. The optimal conditions were using commercial DMF as solvent at 90 o C for 15 h with 8...