Sulfenylating Agents Research Articles

Redox-active alkyl xanthate esters enable practical C–S cross-coupling by nickel catalysis

A new nickel catalysis strategy that harnesses readily accessible alkyl xanthate esters, while previously well-studied as alkyl radical precursors, herein as ideal sulfenylating agents via an unprecedented C–S bond activation pattern.

A Useful Methods of Direct Sulfenylation at the 3-Position of Indoles Employing various Sulfenylating Agents

3-Sulfenylated indoles as a significant heterocyclic scaffold have garnered enormous interest and utility in the past several decades due to significant biological and pharmaceutical activities, including anti-HIV, anti-obesity and anti-cancer activity. To date, several methods have been developed for the synthesis of 3-sulfenylated indoles using distinct sulfenylating agents. In this review, the recent developments in the metal free synthesis of 3-sulfenylated indoles moieties are covered, which show insight into both the large distinct reactions condition as well as mechanism.

Directed, nickel-catalyzed 1,2-alkylsulfenylation of alkenyl carbonyl compounds.

We report a regioselective, nickel-catalyzed syn-1,2-carbosulfenylation of non-conjugated alkenyl carbonyl compounds with alkyl/arylzinc nucleophiles and tailored N–S electrophiles. This method allows the simultaneous installation of a variety of C(sp3) and S(Ar) (or Se(Ar)) groups onto unactivated alkenes, which complements previously developed 1,2-carbosulfenylation methodology in which only C(sp2) nucleophiles are compatible. A bidentate directing auxiliary controls regioselectivity, promotes high syn-stereoselectivity with a variety of E- and Z-internal alkenes, and enables the use of an array of electrophilic sulfenyl (and seleno) electrophiles. Among compatible electrophiles, those with N-alkyl-benzamide leaving groups were found to be especially effective, as determined through comprehensive structure–reactivity mapping.

Metal‐Free Synthesis of β‐Bromoalkenyl Sulfides via Deoxygenative Bromination/Olefination/Sulfenylation of Ketones with Sulfonyl Hydrazides and Pyridinium Tribromide

AbstractA novel metal‐free method for synthesis of β‐bromoalkenyl sulfides via deoxygenative bromination/olefination/sulfenylation process using commercially available ketones, sulfonyl hydrazides and pyridinium tribromide as starting materials has been developed. In this reaction, pyridinium tribromide plays the role of oxidant and substrate, wherein water and molecular nitrogen are generated as environmentally benign by‐products. Preliminary investigation revealed that vinyl bromides were critical intermediate. Importantly, this protocol not only obviates the use of alkynes and traditional sulfenylating agents, but also reveals that ketones can be used as precursors of vinyl bromides.

Iodine-Promoted Deoxygenative Iodization/Olefination/Sulfenylation of Ketones with Sulfonyl Hydrazides: Access to β-Iodoalkenyl Sulfides.

A highly regio- and stereoselective synthesis of β-haloalkenyl sulfides using commercially available ketones and sulfonyl hydrazides as starting materials has been developed. This protocol obviates the need for alkynes and traditional sulfenylating agents and therefore opens up a new door to construct β-iodoalkenyl sulfides in a highly simple manner. This study reveals that ketones could be used as vinyl iodide precursors in organic synthesis.

Enantioselective, Lewis Base-Catalyzed Sulfenocyclization of Polyenes.

A sulfenium-ion-initiated, catalytic, enantioselective polyene cyclization is described. Homogeranylarenes and ortho-geranylphenols undergo polycyclization in good yield, diastereoselectivity, and enantioselectivity. The stereodetermining step is the generation of an enantiomerically enriched thiiranium ion from a terminal alkene and a sulfenylating agent in the presence of a chiral Lewis basic catalyst. The use of hexafluoroisopropyl alcohol as the solvent is crucial to obtain good yields. The thioether moiety resulting from the reaction can be subsequently transformed into diverse oxygen and carbon functionality postcyclization. The utility of this method is demonstrated by the enantioselective syntheses of (+)-ferruginol and (+)-hinokiol.

Copper-catalyzed three-component reaction of imidazo[1,2-a]pyridine with elemental sulfur and arylboronic acid to produce sulfenylimidazo[1,2-a]pyridines

In this work, an efficient copper-catalyzed three-component reaction for the synthesis of sulfenylimidazo[1,2-a]pyridines using elemental sulfur as the sulfenylating agents has been developed. The reaction could proceed smoothly with a high degree of functional group tolerance and provide the desired products in moderate to good yield.

Structural, Mechanistic, Spectroscopic, and Preparative Studies on the Lewis Base Catalyzed, Enantioselective Sulfenofunctionalization of Alkenes.

The full details of mechanistic investigation on enantioselective sulfenofunctionalization of alkenes under Lewis base catalysis are described. Solution spectroscopic identification of the catalytically active sulfenylating agent has been accomplished along with the spectroscopic identification of putative thiiranium ion intermediates generated in the enantiodetermining step. The structural insights gleaned from these studies informed the design of new catalyst architectures to improve enantioselectivity. In addition, structural modification of the sulfenylating agents had a significant and salutary effect on the enantioselectivity of sulfenofunctionalization which was demonstrated to be general for trans disubstituted alkenes. Whereas electronic modulation had little effect on the rate and selectivity, steric bulk on arylsulfenylphthalimides was very beneficial.

I2-Catalyzed sulfenylation of indoles and pyrroles using triethylammonium thiolates as sulfenylating agents.

Readily available triethylammonium thiolates were proven to be new and eco-friendly sulfenylating agents for the efficient and practical construction of sulfenylated indoles and pyrroles (48 examples) with good to excellent yields under metal-free and microwave irradiation conditions. The combination of I2 and DMSO enabled direct C-S bond formation, allowing easy and low-cost access to new functionalized C,S-tethered bisindoles and pyrrole-indole pairs with a wide diversity of substituents. The mechanism involving S-S and S-I bond-forming/breaking events was proposed.

N-Hydroxy sulfonamides as new sulfenylating agents for the functionalization of aromatic compounds.

An unprecedented use of N-hydroxy sulfonamides as sulfenylating agents has been established. In the presence of catalytic amounts of iodine and N-hydroxysuccinimide, N-hydroxy sulfonamides participated in sulfenylation with indoles, 7-azaindole, N-methyl pyrrole, and 2-naphthol to afford structurally diverse thioethers in moderate to excellent yields with very high regioselectivity.

Catalytic Synthesis of 3-Thioindoles Using Bunte Salts as Sulfur Sources under Metal-Free Conditions.

An efficient catalytic method for the synthesis of 3-thioindoles has been successfully developed, which uses odorless, stable, readily available crystalline Bunte salts as the sulfenylating agents, iodine as nonmetallic catalyst, and DMSO as both the oxidant and solvent. This method is practical and environmentally benign in terms of sulfur sources, catalyst, and solvent. The catalytic reaction is selective at the C3 position of indoles and compatible with a wide range of substrates, giving the desired products in good to excellent yields.

I2-Catalyzed Multicomponent Reactions for Accessing Densely Functionalized Pyrazolo[1,5-a]pyrimidines and Their Disulphenylated Derivatives.

New I2-catalyzed multicomponent bicyclization reactions of β-ketonitriles with sulfonyl hydrazides have been established, providing a direct and metal-free access toward unreported pyrazolo[1,5-a]pyrimidin-4-ium sulfonates. The latter could be quantitatively converted into densely functionalized pyrazolo[1,5-a]pyrimidines in the presence of bases. Using sulfonyl hydrazides as a sulfenylating agent, the resulting pyrazolo[1,5-a]pyrimidines enabled I2-catalyzed unprecedented disulphenylations to access fully substituted pyrazolo[1,5-a]pyrimidines through direct C(sp(2))-H bond bifunctionalization.

Microwave-assisted regioselective sulfenylation of indoles under solvent- and metal-free conditions

Formation of 3-sulfenylindoles using sulfinic acid as a sulfenylating agent.

Ammonium Iodide Induced Nonradical Regioselective Sulfenylation of Flavones via a C-H Functionalization Process.

A novel and highly regioselective ammonium iodide-induced nonradical sulfenylation method for the construction of a C-S bond was developed via C-H functionalization. With DMSO or R(1)SO2NHNH2 as a sulfenylating agent, MeS- and R(1)S-substituted flavone derivatives were obtained in good yields. This method enriches current C-S bond formation chemistry, making it a highly valuable and practical method in pharmaceutical industry.

DMSO as oxidant and sulfenylating agent for metal-free oxidation and methylthiolation of alcohol-containing indoles

A new methylthiolation protocol was successfully established for the synthesis of substituted indoles bearing 3-methylthioether moiety, in which new C–S bond and C=O bond were formed using dimethyl sulfoxide as the sulfur source under mild conditions.

Catalytic, enantioselective sulfenylation of ketone-derived enoxysilanes.

A catalytic, enantioselective, Lewis base-catalyzed α-sulfenylation of silyl enol ethers has been developed. To avoid acidic hydrolysis of the silyl enol ether substrates, a sulfenylating agent that did not require additional Brønsted acid activation, namely N-phenylthiosaccharin, was developed. Three classes of Lewis bases—tertiary amines, sulfides, and selenophosphoramides—were identified as active catalysts for the α-sulfenylation reaction. Among a wide variety of chiral Lewis bases in all three classes, only chiral selenophosphoramides afforded α-phenylthio ketones in generally high yield and with good enantioselectivity. The selectivity of the reaction does not depend on the size of the silyl group but is highly sensitive to the double bond geometry and the bulk of the substituents on the double bond. The most selective substrates are those containing a geminal bulky substituent on the enoxysilane. Computational analysis revealed that the enantioselectivity arises from an intriguing interplay among sterically guided approach, distortion energy, and orbital interactions.

ChemInform Abstract: Sc(OTf)3‐Catalyzed Synthesis of Thiosulfonates in Ionic Liquid—Water.

AbstractThe method for the synthesis of various sulfenylating agents of type (III) and (VI) represents an interesting alternative to known procedures.

ChemInform Abstract: A New Procedure for the Conversion of Thiols into Reactive Sulfenylating Agents.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Cascade Heterocyclization in the Reaction of Tetrafluorobenzobarrelene with 3‐Methoxycarbonyl‐2‐pyridinesulfenyl Chloride.

In recent years, we have developed a new approach to the synthesis of sulfur and nitrogen containing hetero cycles based on the polar cycloaddition of hetarenesulfenyl chlorides HetSCl to alkenes, dienes, and acetylenes accompanied by the ring closure through the nitrogen atom of the HetS fragment.1—6 In particular, it was found that the reactions of 2 pyridinesulfenyl chlorides con taining substituents in the pyridine moiety even with rather readily transformable bicyclic olefins, such as norbornene3 and norbornadiene,6 afford exclusively cycloaddition products with retention of the carbon skeleton of the starting unsaturated compound. With the aim of extend ing the synthetic scope of this approach, in the present study we examined the possibility of performing the tandem rearrangement—cyclization reaction with the use of readily available tetrafluorobenzobarrelene (1)7,8 as the model substrate. The choice of diene 1 was determined by the fact that its reactions with various electrophilic reagents, including sulfenylating agents, involve cascade skeletal rearrangements.8—10

Cascade heterocyclization in the reaction of tetrafluorobenzobarrelene with 3-methoxycarbonyl-2-pyridinesulfenyl chloride

In recent years, we have developed a new approach to the synthesis of sulfur and nitrogen containing hetero cycles based on the polar cycloaddition of hetarenesulfenyl chlorides HetSCl to alkenes, dienes, and acetylenes accompanied by the ring closure through the nitrogen atom of the HetS fragment.1—6 In particular, it was found that the reactions of 2 pyridinesulfenyl chlorides con taining substituents in the pyridine moiety even with rather readily transformable bicyclic olefins, such as norbornene3 and norbornadiene,6 afford exclusively cycloaddition products with retention of the carbon skeleton of the starting unsaturated compound. With the aim of extend ing the synthetic scope of this approach, in the present study we examined the possibility of performing the tandem rearrangement—cyclization reaction with the use of readily available tetrafluorobenzobarrelene (1)7,8 as the model substrate. The choice of diene 1 was determined by the fact that its reactions with various electrophilic reagents, including sulfenylating agents, involve cascade skeletal rearrangements.8—10