Sulfenylation Of Indoles Research Articles

Efficient Synthesis of 3-Mercaptoindoles via HI-Promoted Sulfenylation of Indoles with Sodium Sulfinates.

A new direct sulfenylation method of indoles by sodium sulfinates and hydroiodic acid was developed giving variety of 3-sulfenylindoles in high yields under mild conditions without using any catalysts or other additives. In situ-generated RS-I species are supposed to be mainly responsible for the key electrophilic alkyl- or aryl-thiolation process.

Synthesis of novel indole‐oxadiazole molecular hybrids by a regioselective C‐3 sulfenylation of indole with 1,3,4‐oxadiazole‐2‐thiols using iodine‐dimethyl sulfoxide and their anticancer properties

AbstractNovel indole‐oxadiazole molecular hybrids have been synthesized by a regioselective C‐3 sulfenylation of indoles with 1,3,4‐oxadiazole‐2‐thiols for the first time using iodine as a catalyst and DMSO as a co‐oxidant. No other regioisomeric products were formed when the 3‐position of the indole is substituted. The method is mild and highly efficient with good substrate tolerance in both components. The indole‐oxadiazole hybrid compounds are tested for their antiproliferative activities against human breast carcinoma cell line MCF‐7 and a set of hybrids is identified as having moderate growth inhibition with IC50(10–25 μM). The indole‐oxadiazole hybrid3gcshowed the most significant cell proliferative activity against the MCF‐7 cell line with IC5010 μM.

Iodine‐catalyzed Regioselective Electrophilic (Fluoroalkyl) Sulfenylation of Indoles with (RSO2)2O via Deoxygenative Reduction

AbstractA method for electrophilic C−H sulfenylation by deoxygenative reduction from less expensive and easily available sulfonic anhydrides is reported. This C−S bond‐forming reaction allows a general access to sulfenyl electrophiles, including important trifluoromethyl, perfluoroalkyl and aryl derivatives that are otherwise difficult to afford. Under metal‐free conditions, the reaction yielded 3‐arylthio (Fluoroalkylthio) indoles in good to excellent yields. The catalytic technique tolerates a wide range of functional groups.

S-Protected Cysteine Sulfoxide-Enabled Tryptophan-Selective Modification with Application to Peptide Lipidation.

Lipidation of peptides is a promising means of modification that can improve the therapeutic character of biologically active peptides. Here, a novel lipidation protocol for peptides is described. The C-H sulfenylation of indole in peptides using S-p-methoxybenzyl cysteine sulfoxide under acidic conditions in the presence of ammonium chloride, anisole, and triisopropylsilane enables late-stage tryptophan-selective peptide lipidation. This developed protocol has been used successfully for the lipidation of glucagon-like peptides. Oral glucose tolerance tests in wild-type mice indicated that the resulting lipidated peptides stimulate insulin secretion and exhibit a more long-lasting blood-glucose-lowering effect than a parent nonlipidated peptide.

XtalFluor‐E Enabled Regioselective Synthesis of Di‐Indole Sulfides by C3−H Sulfenylation of Indoles

AbstractA simple, regioselective synthesis of di‐indole sulfides by electrophilic aromatic substitution of the C3‐position of indoles was achieved using Xtalfluor‐E as the sulfenylating reagent. The addition of amine bases was found to have a significant effect on the reaction outcome, with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) switching off the reactivity of XtalFluor‐E, while the hindered base 2,6‐ditertbutyl‐4‐methylpyridine (DBP) led to the formation of two di‐indole‐sulfur containing products, one S(II) and one S(IV). The optimal base for accessing the di‐indole sulfides in high yield proved to be Hünigs base, EtNiPr2. While this amine formed a Lewis adduct with XtalFluor‐E, adduct formation did not completely quench electrophilic reactivity indicating reversible coordination to the sulfur center. This is the first report utilizing XtalFluor‐E in electrophilic aromatic substitution to form C−S bonds to our knowledge, and this process is applicable to a wide range of functionalized indoles and does not require N1‐protection.

Direct Access to Fluorinated Sulfonylhydrazides and Study of Their Reactivity in Thiolation Reaction on Indoles

AbstractA new family of fluorinated sulfonyl hydrazides has been easily prepared from accessible and cheap sulfinates and azodicarboxylates. In addition, trifluoromethylsulfonyl hydrazide (Tf(Boc)N−NHBoc) is an effective source of SCF3 in the sulfenylation of indoles.

Catalytic Electrophilic C–H Sulfenylation of Indoles with Disulfides under Ball Milling

Inspired by mechanic force induced S–S bridge activation in a protein context, we have developed the first mechanochemical electrophilic C–H sulfenylation of indoles in combination with iodine cata...

Recyclable Cellulose-Derived Fe3O4@Pd NPs for Highly Selective C–S Formation by Heterogeneously C–H Sulfenylation of Indoles

An efficient and convenient method was developed for the preparation of 3-sulfenylindoles via a cellulose-derived Fe3O4@Pd NPs catalyzed heterogeneously C–H sulfenylation of indoles. This approach provides an effective synthetic route to an important class of indoles derivatives and features high efficiency, easy operation, good practicality, and environmental friendliness. The recoverable catalyst was separated from the reaction mixture using an outside magnetic field and can be recycled five times without huge loss of catalytic performance. An efficient method was developed for the preparation of 3-sulfenylindoles via cellulose-derived Fe3O4@Pd NPs catalyzed heterogeneously C–H sulfenylation of indoles.

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 °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)2O 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-(1 H-triazole-1-yl)-3-arylthio indole, which is an analogue of the potent indole-based anticancer agent.

Accounting for Different Reactivities of Sulfinate and Thiosulfate Salts in Regioselective Azetidine Coupling via C–H Sulfenylation of Indoles

The regioselective incorporation of azetidines into heteroaromatic compounds is reported via a formal C–H sulfenylation reaction. While sodium sulfinate salts undergo C3 sulfenylation of electron-rich indoles only, the corresponding thiosulfate salts have proved to be more generally useful. A mechanistic hypothesis for the different reactivities of sulfinate and thiosulfate salts is provided.

Photocatalytic direct C–S bond formation: facile access to 3-sulfenylindoles via metal-free C-3 sulfenylation of indoles with thiophenols

An efficient and convenient photocatalytic direct C-3 sulfenylation of indoles with thiophenols has been developed for the construction of 3-sulfenylations.

Silver-Mediated Sulfenylation of Indoles and Benzimidazoles with Di(hetero)aryl Disulfides

Silver-Mediated Sulfenylation of Indoles and Benzimidazoles with Di(hetero)aryl Disulfides

ChemInform Abstract: Microwave‐Assisted Synthesis of 3‐Sulfenylindoles by Sulfonyl Hydrazides Using Organic Ionic Base‐Broensted Acid.

AbstractSulfenylindoles are prepared via a DBU‐based ionic liquid‐promoted sulfenylation of indoles using sulfonyl hydrazides as thiol surrogate.

Cooperative catalysis by bovine serum albumin-iodine towards cascade oxidative coupling-C(sp(2))-H sulfenylation of indoles/hydroxyaryls with thiophenols on water.

Cooperative cascade catalysis by bovine serum albumin (BSA)-iodine allows for the first time the performance of C(sp(2))-H sulfenylation of indole from readily available thiophenol (-SH bond) via in situ generation/cleavage of disulfide (S-S bond) in air under aqueous conditions, whereas BSA or I2 individually do not permit this two step sequence to occur in the same pot towards C-S bond formation. This green cooperative protocol is extendable to sulfenylation of hydroxyaryls (i.e. 2-naphthol or 4-hydroxycoumarin) with diverse thiols (aryl/heteroaryl) without using any toxic metal catalysts, bases or oxidants, thus rendering the process environmentally and economically reliable. Further, the gram scale synthesis of a COX-2 inhibitor (3-(pyridin-2-ylthio)-1H-indole), regioselectivity and recyclability (up to four cycles) are the additional merits of this cooperative cascade bio-chemocatalytic (BSA-I2) protocol. Moreover, HPLC and ESI-MS provide powerful insights into the mechanistic aspects of the above cascade sulfenylation reaction.

ChemInform Abstract: A Base‐Mediated Mild Sulfenylation of Indoles and Pyrrole with α‐Acylthiones.

AbstractIndole derivatives react with 1 equiv.

Metal free sulfenylation and bis-sulfenylation of indoles: persulfate mediated synthesis

A method which avoids metal and halogen for the synthesis of 3-arylthioindoles from indoles and diaryl disulfides using ammonium persulfate in methanol has been presented. Moreover, double C-H sulfenylation of indoles at 2 and 3-positions has also been achieved using iodine and ammonium persulfate.

A Metal‐Free Sulfenylation and Bromosulfenylation of Indoles: Controllable Synthesis of 3‐Arylthioindoles and 2‐Bromo‐3‐arylthioindoles

AbstractAn efficient metal‐free sulfenylation of indoles with disulfides has been developed, leading to 3‐arylthioindoles in moderate to excellent yields. Furthermore, bromosulfenylation of indoles with disulfides has been realized for the first time providing a new family of 2‐bromo‐3‐arylthioindole derivatives in good yield by the one‐pot construction of CS and CBr bonds. It is noteworthy that the system enables the use of both the RS moieties in RSSR and shows a broad functional group tolerance.

ChemInform Abstract: Iron‐Catalyzed Sulfenylation of Indoles with Disulfides Promoted by a Catalytic Amount of Iodine.

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Development of a Novel, Highly Efficient Halide‐Catalyzed Sulfenylation of Indoles.

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Vanadium‐Catalyzed Sulfenylation of Indoles and 2‐Naphthols with Thiols under Molecular Oxygen.

AbstractFor Abstract see ChemInform Abstract in Full Text.