AcBr/DMSO Mediated Sulfenylation of Pyrrolo[2,1-a]isoquinolines

Abstract

We have developed a mild sulfenylation of pyrrolo[2,1-a]isoquinolines with acetyl bromide and dimethyl sulfoxide. A wide range of functionalized pyrrolo[2,1-a]isoquinolines could be prepared efficiently through the formation of a C–S bond with thiophenols (27 examples, 36–94% yields). The current strategy can also be utilized for functionalization of pyrrolo[1,2-a]quinolines and indole.

POCl3/Sulfoxide and AcCl/Sulfoxide Mediated Chlorination of Pyrrolo[2,1-a]isoquinolines

“…Interestingly, as shown in Scheme 5, thioether 6 has been isolated in excellent yield through aromatic nucleophilic substitution reaction by heating a mixture of chloride 3p with 3 equiv of thiophenol in PhCl at 120 °C for 18.2 h. 16 To probe the mechanism proposal, we have conducted several experiments as shown in Scheme 6. No reaction occurred in the absence of sulfoxide 2a, suggesting that sulfoxide should be essential for the generation of "Cl + " species (eq 1).…”

“…Known compound . White solid, 46.6 mg, 93%; Purified by a silica gel flash chromatography (Hexane/EtOAc = 49:1); 1 H NMR (400 MHz, CDCl 3 ) δ 8.27 (d, J = 7.5 Hz, 1H), 7.67–7.61 (m, 2H), 7.56 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.39–7.33 (m, 3H), 7.25–7.19 (m, 1H), 7.07–7.00 (m, 4H), 6.91 (d, J = 7.5 Hz, 1H), 3.66 (s, 3H), 2.27 (s, 3H).…”

“…We failed to chlorinate pyrroloisoquinoline with FeCl 3 , and only chlorinated polysubstituted pyrroles were obtained instead . On the basis of recent achievements and our studies, − we hypothesized that chloronium intermediate might be generated in situ by choosing a suitable chlorine source and activator for sulfoxide. To the best of knowledge, the chemistry of pyrrolo­[2,1- a ]­isoquinoline has not been fully stressed as that of indole, pyrrole, and isoquinoline.…”

“…Bromodimethylsulfonium was proposed as the real brominating agents according to our results and previous reports. Interestingly, the addition of thiophenol to the AcBr/DMSO reaction system led to a chemoselective sulfenylation reaction . In contrast, the combination of AcCl and DMSO resulted in a cascade methylenation sequence .…”

“…Interestingly, the addition of thiophenol to the AcBr/ DMSO reaction system led to a chemoselective sulfenylation reaction. 16 In contrast, the combination of AcCl and DMSO resulted in a cascade methylenation sequence. 17 We failed to chlorinate pyrroloisoquinoline with FeCl 3 , and only chlorinated polysubstituted pyrroles were obtained instead.…”