Iron-catalyzed tandem reaction of C–Se bond coupling/selenosulfonation of indols with benzeneselenols

An iron-catalyzed tandem reaction of C–Se bond coupling/selenosulfonation was developed. Starting from sample indols and benzeneselenols versatile biologically active 2-benzeneselenonyl-1H-indoles derivatives were efficiently synthesized. The reaction mechanism was studied by the deuterium isotope study and in situ ESI-MS experiments. This protocol features mild reaction conditions, wider substrate scope and provides an economical approach toward C(sp2)–Se bond formation.

and additive, which produced the product 3a with an 83% yield (entry 14). It was also noted that the product yield was decreased when the reaction temperature was less or greater than 80 C (entries 15 and 16). Furthermore, the results also show that the reaction yield of 1,4-dioxane as a solvent is higher than that of other solvents (entries 17 and 18). In particular, those reactions had to be carried out under a strict anhydrous condition. The presence of water would reduce the Fe 3+ concentration, and reduced the catalytic activity (entry 19). Thus, the optimum reaction condition was determined as the 1a and 2a ratio of 1 : 1.5 in the presence of FeCl 3 (5 mol%), DBU (2 equiv.), at 80 C for 10 hours (Table 1, entry 14).
Next, the reaction scope was been screened, a wide array of indols 1 with benzeneselenols 2 were subjected to this reaction and given the products 3 in good to excellent yields (Table 2, 65-92% yield). It was found that both the electron-donating and electron-withdrawing indols derivatives 1 reacted smoothly with benzeneselenols 2. Furthermore, indols 1 bearing electronwithdrawing groups showed better activity than bearing electron-donating groups. Benzeneselenols 2 bearing electrondonating groups showed better activity than bearing electronwithdrawing groups. To our delight, despite the electronwithdrawing effect of -NO 2 and -CF 3 group is so strong, the corresponding products 3h and 3r were still obtained in 75% and 69% yield (entries 8 and 9).
Furthermore, we next focused on evaluating the generality of tandem reaction of C-Se bond coupling/selenosulfonation by using a series of pyrroles. To our delight, N-methylpyrrole 4 with benzeneselenols 2 successfully provided the corresponding products 5 (Table 3, 59-79% yield). For both substrates, this reaction was amenable when electroneutral group (entry 1), electron donating group (entries 2 and 3), electron-withdrawing group (entry 4-8), Moreover, the triuoromethyl substituted delivered the product 5h exclusively in 59% yield which bearing of strong electron-withdrawing group. Furthermore, reactants with more complex substituents also perform smoothly (entry 9). Both the results demonstrated the good generality and high functional group tolerance of this method.
To obtain the preliminary data of the mechanism, some addition reactions were been done (Scheme 1). At rst, the model reaction (Scheme 1I) was conducted in two separate steps: the C-Se cross coupling reaction of 6 with 2a given a product 7 (Scheme 1II, 85% yield). 11 Next, 7 was reacted under our standard conditions, the reaction successfully obtained the target product 3a (Scheme 1III 79% yield), indicating that the intermediate 7 was involved in the reaction mechanism.
Next, we used isotope experiments to further study the reaction mechanism, as shown in Scheme 2. The kinetic deuterium isotope effects 12 observed in the control experiments were indicated that the C(sp 2 )-H cleavage being the ratelimiting step (k H /k D ¼ 1.3, for detail information please see ESI †). Additionally, the model reaction mixture 13 was subjected to the in situ ESI-MS analysis which the detection temperature was enacted at 120 C (Scheme 3). The positive-ion mode ESI-MS showed a peak at 296.0 (m/z) which corresponding to [C 14 H 11 -NNaSe] + . The peak at 328.0 was assigned to [C 14 H 11 NNaO 2 Se] + (Scheme 3a). Meanwhile, using the 18 O 2 deuterium labeling study gave a peak at 331.9 was assigned to [C 14 H 11 NNa 18 O 2 Se] +

Conclusions
In summary, we have reported an iron-catalyzed tandem reaction of C-Se bond coupling/selenosulfonation. Starting from sample indols and benzeneselenols versatile biologically active 2-benzeneselenonyl-1H-indoles derivatives were efficiently synthesized. The reaction mechanism was studied by the deuterium isotope study and in situ ESI-MS experiments. This protocol features mild reaction conditions, wider substrate scope and provides an economical approach toward C(sp 2 )-Se bond formation.

Conflicts of interest
There are no conicts to declare.