Synergistic Dual Role of [hmim]Br-ArSO2Cl in Cascade Sulfenylation–Halogenation of Indole: Mechanistic Insight into Regioselective C–S and C–S/C–X (X = Cl and Br) Bond Formation in One Pot

Bifunctionalized indoles are an important class of biologically active heterocyclic compounds and potential drug candidates. Because of the lack of efficient synthetic methods, one pot cascade synthesis of these compounds is rare and remains a challenge. To expand this field, we herein disclose a step-economical and temperature tunable strategy wherein the synergistic effect between [hmim]Br-ArSO2Cl leads exclusively to the formation of 3-arylthio indole via sulfenylation of indole at room temperature, while heating the reaction mixture at 50 degrees C provided an unexpected 2-halo-3-arylthio indole with construction of C-S and C-S/C-X (X = Cl and Br) bonds without addition of any external halogenating agent via cascade sulfenylation-halogenation reactions under metal-oxidant-base-free conditions. Further, insight into the reaction mechanism provides an unprecedented observation wherein the synergistic interaction between [hmim]Br-ArSO2X in the presence of a catalytic amount of water generates arylsulfonic anhydride (ArSO2)(2)O in situ as a new sulfur source along with the formation of [hmim]PTS as probed by NMR, ESI-MS, DART-MS, and HPLC studies. Notably, the mixture of bifunctionalized 2-halo(Br/Cl)-3-arylthio indole was smoothly diversified with privileged heterocycle triazole to provide 2-(1H-triazole-1-yl)-3-arylthio indole, which is an analogue of the potent indole-based anticancer agent.