The reactivity of N-thiophthalimides with silyl chalcogenides is described. Treatment of N-thiophthalimides with bis(trimethylsilyl) sulfide [(Me3Si)2S] leads to the formation of a mixture of the corresponding disulfides and trisulfides. On the other hand, N-thiophthalimides react with bis(trimethylsilyl) selenide [(Me3Si)2Se] under TBAF catalysis to smoothly give variously substituted diaryl, divinyl, and dialkyl disulfides; formation of a selenotrisulfide (dithiaselane, RSSeSR) is rationalized as an intermediate. Exploiting the different chemical behavior of silyl chalcogenides, we have disclosed a novel, selective, and operationally simple method to access disulfides in good yields under mild conditions.

A new methodology for the synthesis of small molecules containing the S-Se bond is reported. Aryl-and alkyl-selenols react smoothly with N-thiophthalimides to afford the corresponding selenenylsulfides through a clean S N 2 path occurring at the sulfur atom. The reaction proceeds under very mild conditions in DMF in absence of catalysts for most of the substrates. The scope of the reaction was found to be broad, allowing a wide series of selenols and N-thiophtalimides to be efficiently employed in this procedure. Owing to the instability of the S-Se bond, selenenylsulfides exhibited a remarkable tendency to disproportionate to the corresponding symmetric diselenides and disulfides. Preliminary evaluation of the catalytic antioxidant properties of novel selenenylsulfides showed their behaviour as GPx mimics.Catalysts 2019, 9, 333 2 of 11 a second equivalent of GSH, to reform the selenol, together with oxidized glutathione GSSG. The selenenylsulfide, containing the Se-S bridge, represents the key intermediate for the activity of the enzyme [7,[16][17][18][19]. Taking into account the importance of this process, several synthetic approaches to obtain selenated small molecules as enzyme mimics have been developed. However, to the best of our knowledge, a limited number of methods are reported for the preparation of selenenylsulfides. These methods typically exploited the reactivity of diselenides in thiol-diselenide exchange or foresee the reaction of sulfenyl derivatives with thiols [16,17,[20][21][22].It is well established that the Se-S bridge is unstable and undergoes disproportionation reaction to afford diselenides and disulfides. Some examples are reported on selenenylsulfides stabilized by sterically bulky groups or by intramolecular Se . . . Het (N, O) interactions [23].Owing to the interest in these selenium containing compounds, the search for novel procedures to prepare small molecules containing the Se-S unit is of great interest.Our long-dated interest in the chemistry of silyl chalcogenides allowed to disclose novel procedures to access a plethora of sulfur and selenium containing molecules exploiting the nucleophilic behaviour of the chalcogen atom towards various electrophiles [24][25][26][27][28][29]. Recently we reported the reaction of bis(trimethylsilyl)selenide (HMDSS) with N-thiophtalimides as a mild, general metal free procedure for the synthesis of variously substituted disulfides [30].Indeed, despite the interest in the reactivity of selenols as nucleophilic selenium transfer reagents, their use has been critically limited by their instability. However, HMDSS was efficient in the opening of ring strained heterocycles, namely epoxides, episulfides and aziridines, leading to a wide range of β-functionalized selenols, which were stable enough to react with electrophiles under controlled catalytic conditions [31]. Differently substituted stable aryl selenols were also prepared by reduction of the parent diselenides to explore their activity as enzyme inhibitors [32].On the basis of our findings ...