Metal- and base-free syntheses of aryl/alkylthioindoles by the iodine-induced reductive coupling of aryl/alkyl sulfonyl chlorides with indoles

Abstract

An Iodine-catalysing process for an efficient and scalable sulfenylation protocol for indoles employing aryl-/ alkyl sulfonyl chlorides has been developed. A series of sterically and electronically divergent aryl-/ alkyl sulfonyl chlorides were participated in the sulfenylation of C(sp 2 )-H bonds, resulting in a high to excellent yield of indole 3-sulfenylether molecules. It is noteworthy that indole-3thiomethyl ether is efficiently generated with methanesulfonyl chloride as an electrophile, indicating the potential of this methodology.

Synergistic Cooperative Effect of Sodium borohydride‐Iodine Towards Cascade C−N and C−S/Se Bond Formation: One‐pot Regioselective Synthesis of 3‐Sulfenyl/selenyl Indoles and Mechanistic Insight

“…In general, two synthetic routes have been known in the literature for synthesis of chalcogenylated indoles (Scheme ) in which the first route involves direct chalcogenylation of an existing indole ring with sulfenylating agents whereas other route involves cascade electrophilic cyclization and coupling reactions of various designer aniline derivatives (such as 2‐alkynyl aniline or 2‐vinyl aniline) followed by subsequent chalcogenylation. Despite the fact that there are a wide range of sulphur sources (such as arylsulfenyl/sulfonyl halides, and arylsulfonium salts which contribute immensely in the first route during direct chalcogenylation of pre‐existing indoles with C−S bond formation (Scheme , Route – 1), however, many commercially available indole derivatives are either expensive or possessing limited scope in structural diversity besides some of sulphur sources requires some additional step to prepare or are sensitive to moisture. Against this milieu, the second cascade route offers advantage in a way to design a mild, efficient and diversified method for the simultaneously constructing the substituted indole nucleus and subsequent chalcogenylation with C−N and C−S bond formation in one manoeuvre (Scheme , Route – 2).…”

“…With remarkable success towards synthesis of sulfenylating agent. (Table , 29 examples of 3‐sulfenylated indoles), now our attention turned towards further widening the scope and compatibility of commercially available other sulfenylating agents– (such as sulfonylhydrazide, sulfonylchlorides, sulfinate and disulfide derivatives) in optimized reaction condition (Scheme ). Among them, sulfonylhydrazide provided 3 e in poor yield (29%) whereas p ‐tolyl disulfide appears as an effective sulphur source which successfully reacts with 1 a to provide the desired product 3 e in 67% yield (Scheme ) which is comparable in respect to yield of 3 e as obtained using thiophenol (68%, Table ) as a sulfenylating agent.…”

Sustainable and Site‐Selective C−H Sulfenylation of Aromatic Compounds with Thiol using Catalytic Graphene Oxide and NaI

“…Considering the toxicity as well as a high cost of various transition‐metal‐based catalysts, metal‐free approaches have also been developed. The most common is to use iodine in the presence of thiol, or other sulfur‐based reagents like disulfide, sulfinate, sulfonyl chloride, sulfonyl hydrazide . However, most of these conditions using thiols require the presence of an oxidant, such as tert ‐butyl hydroperoxide (TBHP), hydrogen peroxide (H 2 O 2 ), or DMSO –.…”

“…However, most of these conditions using thiols require the presence of an oxidant, such as tert ‐butyl hydroperoxide (TBHP), hydrogen peroxide (H 2 O 2 ), or DMSO –. Moreover, the use of different sulfur‐based reagents other than thiol generate by‐products resulting in lower atom economy of the reaction as well as difficulty in separation . Although the use of aromatic thiols in the regioselective sulfenylation appears to be atom‐economic, the presence of strong oxidants limits for their versatile applications .…”

Efficient C3-alkylsulfenylation of indoles under mild conditions using Lewis acid-activated 8-quinolinethiosulfonates.

“…Coordination of a Lewis acid to the quinoline nitrogen indeed enhances the electrophilicity of the sulfur compared to standard thiosulfonates. Phtal-SR 0.9 indole, 0.5% MgBr2, DMAc, 90°C [6a] Me,,Et, cHex, iPr MBT-SR 0.9 indole, 10% CuI, DMSO, rt [11] Et, Bz RSO2Cl 2 indole, 10 % I2, 80°C, 1,4-dioxane [12] 0.5 indole, 1.5 TBAI, 60°C, DMF [10b] Me, Bn, n-Bu Et, i-Pr RSO2H 0.8 indole, 1 TBAI, 0.3 TsOH, 110 W, 70°C [13] Me, n-Oct RSO2Na 0.8 indole, 8% I2, 2 H2O2, 2.6 diethylphosphite, PEG400, 100W, 70°C [10c] 0.5 indole, 5% I2, 1.5 DMSO, 1 diethylphosphite, 100°C, anisole under argon [10d] Me Me ,Et, Pr RS-SR 1 indole, 5% I2, 3 DMSO, 100 W, 80°C [9] Et, Bn RSO2SR…”