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Sulfonyl fluorides have widespread applications in many fields, including organic synthesis, chemical biology, drug discovery and materials science. In particular, in the past decade, a number of aliphatic sulfonyl fluorides have been identified showing various biological activities. These applications and appealing features of sulfonyl fluorides have brought about a significant advancement in developing synthetic methods to access sulfonyl fluorides. In this review, we will discuss the recent developments of radical approaches for the synthesis of aliphatic sulfonyl fluorides. [ABSTRACT FROM AUTHOR]

Sulfonyl fluorides have found diverse applications in multiple disciplines due to their reactivity and stability. Thus, exploiting the new reactivity of sulfonyl fluorides is of high importance to Sulfur (VI) Fluoride Exchange (SuFEx) chemistry. Reported herein is a three‐component reaction of β‐keto sulfonyl fluorides, arynes and DMF for the streamline synthesis of sulfocoumarins. The reaction proceeds by trapping of the in situ generated o‐quinone methides with β‐keto sulfonyl fluorides, followed by selective cyclization with sulfonyl fluorides. This strategy provides a new avenue to access diverse sulfocoumarins with under mild conditions. [ABSTRACT FROM AUTHOR]

The Friedel‐Crafts sulfonylation for the synthesis of diaryl sulfones derivatives was achieved by using triflic acid (TfOH) as the acidic catalyst with aryl sulfonyl chlorides and arenes at elevated temperatures. Different sulfones could be synthesized with this method in good to excellent yield and with high selectivity. In contrast to the previous methodology reported for this sulfonylation, the catalyst and the excess of arene could be easily recovered and re‐used in further batches. [ABSTRACT FROM AUTHOR]

Introduction of a 1,3‐diene moiety at the C3‐position of pyrrole and indole bearing various aliphatic as well as aromatic functional groups with good stereoselectivity remains a challenging task. Keeping the synthetic applicability in mind, an eccentric strategy is developed to synthesize 1,3‐dienyl pyrroles and indoles from unprotected pyrroles and indoles employing β‐sulphonyl aldehyde as a dienylating agent. This method is developed by using a one‐pot sequential Brønsted acid/base catalysis strategy. The nucleophilicity of indole is transmitted through the conjugation to eliminate the sulfonyl groups in a step‐wise manner. Further, this developed protocol was extended to the incorporation of a 1,3,5‐triene moiety at the C3‐position of indoles through unprecedented successive three sulfonyl group elimination. As an application of this strategy, a Diels−Alder reaction and hydrothiolation of 1,3‐diene were demonstrated. [ABSTRACT FROM AUTHOR]

A water‐promoted synthesis methodology for constructing 3‐sulfone propionic acids from sulfonyl hydrazides and α, β‐unsaturated propionic acids with excellent yields were reported. The green synthesis methodology was promoted by water without any catalyst, ligand and organic solvent. The D2O control experiment sufficiently proved that the 2‐hydrogen atom of 3‐sulfone propionic acid come from water. Moreover, the 3‐sulfone propionic acid derivates could be directly purified by crystallization without column chromatography. [ABSTRACT FROM AUTHOR]

N‐Glycosyl N‐sulfonyl amides have been synthesized by a self‐promoted glycosylation, i. e. without any catalysts, promotors or additives. When the reactions were carried out at lower temperatures a mixture of N‐ and O‐glycosides were observed, where the latter rearranged to give the β‐N‐glycosides at elevated temperatures. By this method sulfonylated asparagine derivatives can be selectively β‐glycosylated in high yields by trichloroacetimidate glycosyl donors of different reactivity including protected glucosamine derivatives. The chemoselectivity in the glycosylations as well as the rearrangements from O‐glycosides to β‐N‐glycosides gives information of the glycosylation mechanism. This method gives access to glycosyl sulfonyl amides under mild conditions. [ABSTRACT FROM AUTHOR]

An efficient chemoselective protocol has been developed for the synthesis of thiosulfonates and thiocyanates by employing cost effective and commercially available organosulfonyl chlorides with potassium thio‐/selenocyanate. The strategy offered the thiosulfonates and thiocyanates selectively by tuning the equivalents of KSeCN and optimizing the reaction temperature. On the other hand, thiosulfonates were obtained as sole products when organosulfonyl chlorides were treated with KSCN. Furthermore, the syntheses of diarylthioethers and aryl(heteroaryl) thioethers were carried out as a part of synthetic application of newly prepared arylthiocyanates. [ABSTRACT FROM AUTHOR]

Sulfonylureas are employed in a variety of applications including use as drugs to treat type II diabetes and as plant growth regulators or herbicides. Traditionally, the synthesis of sulfonylureas has been accomplished either by the treatment of sulfamides with isocyanates in the presence of a base or through sulfonamides conversion into N‐sulfonyl isocyanates or N‐sulfonyl carbamate derivatives which provide the corresponding sulfonylureas upon treatment with amines. Both approaches are severely limited by the weak nucleophilicity of sulfamides and by the difficulty in synthesizing and handling isocyanate species. Such a drawback could be mitigated by the emergence of protocols establishing the labile electrophilic functional groups in situ so that their coupling with nucleophilic partners takes place in one‐pot. Recently, the development of environmentally friendly methods to prepare sulfonylurea containing compounds without using harmful reagents has attracted considerable attention. The aim of the minireview is to explore the different protocols emerged in the literature to generate sulfonylureas giving importance to the reaction mechanisms of crucial synthetic steps. [ABSTRACT FROM AUTHOR]

An efficient iodine-mediated coupling of cyclic amines with sulfonyl hydrazides is reported. This transformation opens a new route to the synthesis of vinyl sulfones derivatives, which is a common structural motif in natural products and pharmaceuticals. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process. [ABSTRACT FROM AUTHOR]

Amino acid‐based dithiocarbamates were introduced as efficient intermediates for the synthesis of a diverse library of novel di‐ and tri‐substituted thiazoles via condensation with various reagents such as anhydrides, acyl halides, benzene sulfonyl chloride, trifluoromethanesulfonic anhydride, chloroethyl formate, and diethyl chlorophosphate. The utilities of adducts in further organic synthesis were confirmed by Sonogashira and oxidation reactions. In addition, reaction of aspartic acid‐based dithiocarbamates with anhydrides affords the corresponding fused 6,6a‐dihydrofuro[3,2‐d]thiazol‐5(3aH)‐ones diastereoselectively in excellent yields. [ABSTRACT FROM AUTHOR]

Compounds containing S–X (X = N, P, O) bonds are commonly found in organic synthesis, medicinal chemistry and pesticide chemistry. The use of transition metal catalysts enables the development of more efficient and environmentally friendly synthetic processes. The reaction strategy between sulfur sources (such as sulfenyl or sulfonyl compounds) and organic substrates (such as amines, phosphites, or alcohols) is one of the most important methods to give S–X (X = N, P, O) bond. Herein, we summarize the recent research progress on the S–X (X = N, P, O) bond formation catalyzed by transition metals, mainly starting from sulfur sources containing sulfenyl or sulfonyl group. [ABSTRACT FROM AUTHOR]

An iodine‐catalyzed [3+2] cycloaddition/ring opening reaction of 1,1‐diacylcyclopropanes with sulfonyl hydrazides has been reported. In the presence of 20 mol‐% iodine, a range of structurally diverse fully substituted pyrazoles with a hydroxy functional group are obtained in moderate to excellent yields with extremely high regioselectivity. [ABSTRACT FROM AUTHOR]

A simple and practical synthesis of sulfonyl fluorides from sulfonamides is reported. The method capitalizes on the formation of the sulfonyl chloride by virtue of the reaction of Pyry‐BF4 and MgCl2, and subsequent in situ conversion to the more robust and stable sulfonyl fluoride by the presence of KF. The mild conditions and high chemoselectivity of the protocol enable the late‐stage formation of sulfonyl fluorides from densely functionalized molecules. [ABSTRACT FROM AUTHOR]

A convenient approach to 1,3‐bifunctional sulfonyl fluorides, sulfonamides and sulfinates bearing a bicyclo[1.1.1]pentane unit attached to the sulfur atom and (protected) amino or carboxyl group is described. The method relied on photochemical decomposition of Barton [1‐hydroxypyridine‐2(1H)‐thione] esters of the corresponding carboxylic acids as the key step, followed by oxidation and cleavage of the 2‐pyridyl moiety. The title building blocks were obtained on a gram scale, and their utility was demonstrated by preparation of an isosteric analogue of classical sulfonamide anitibiotic sulfanilamide, as well as some other common chemical modifications. [ABSTRACT FROM AUTHOR]

An oxidative coupling of NH‐sulfoximines and arylsulfinates catalyzed by of I2 and H2O2 affords N‐sulfonyl sulfoximines. The reaction proceeds under aerobic conditions in water at room temperature. The merits of this protocol include mild metal‐free reaction conditions, a green and cheap solvent, safe and simple operation, good yields, and a wide substrate scope. [ABSTRACT FROM AUTHOR]

A strategy for the rapid synthesis of 3‐substituted N‐sulfonyl pyrazoles via p‐TSA‐promoted cyclization reactions of sulfonyl hydrazines with N,N‐dimethyl enaminones has been developed. This method achieves both the formation of pyrazole ring and the continued retention of sulfonyl group, providing a series of 3‐substituted N‐sulfonyl pyrazoles in moderate to good yields with good functional group tolerance, easily available starting materials, and can be scaled‐up. [ABSTRACT FROM AUTHOR]

A metal‐free method for reduction of cyclic N‐sulfonyl ketimines catalyzed by B(C6F5)3, using commercially available methylphenylsilane as a reducing reagent under mild conditions has been developed. This reductive protocol was effective, not only providing the expected cyclic N‐sulfonamides in good to excellent yields, but also showing good functional‐group tolerance. [ABSTRACT FROM AUTHOR]

Highly regioselective synthetic methodology leading to densely functionalised C(3), C(4) and C(5) substituted pyrazoles 10a–q, 14a‐i and 16a–g via thermal [3+2]‐dipolar cycloaddition, of α‐diazoacetates and α‐thio‐β‐chloroacrylamides, at the sulfide, sulfoxide and sulfone levels of oxidation, is described. This method allows access to C(4)‐sulfenyl or sulfonyl pyrazoles, through migration of the sulfur substituent at the sulfide and sulfone oxidation levels, while elimination of the sulfinyl group leading to 3,5‐disubstituted pyrazoles, is observed. While the sulfide migration is readily rationalised, the carbon to carbon 1,2‐sulfonyl migration is unprecedented and mechanistically intriguing. The synthetically versatile generation of densely functionalised pyrazoles containing substituents amenable to further modification offers advantages over alternative synthetic routes. Isolation of the N‐alkylated pyrazoles 11a and 12a as by‐products from the cycloaddition through further reaction of the pyrazoles 10 with excess α‐diazoacetate, proved useful in rationalising the tautomeric behaviour evident in the NMR spectra of the pyrazoles, with the position of tautomeric equilibrium influenced by solvent and substituents. [ABSTRACT FROM AUTHOR]

An efficient method for the asymmetric hydrogenation of cyclic and acyclic N‐sulfonylimines co‐catalyzed by Pd/Zn(OTf)2 using hydrogen gas under ambient pressure was developed. The methodology offers an easy access to generate chiral sulfonylamines in good yields and excellent enantioselectivities. Chiral sulfonylamines can be efficiently synthesized in good yields by asymmetric hydrogenation of cyclic and acyclic N‐sulfonylimines co‐catalyzed by Pd/Zn(OTf)2 using hydrogen gas under ambient pressure. [ABSTRACT FROM AUTHOR]

We developed a silver‐catalyzed strategy for the generation of sulfonyl radicals from sulfonamides derived from α‐amino acids. The reaction proceeded via a decarboxylation, N–S bond cleavage and radical cyclization sequence and allows the difunctionalization of alkynes and the synthesis of 3‐sulfonylated coumarins. The reaction tolerated a broad scope of substrates and functional groups and could be extended to the synthesis of oxindoles and an isoquinolinedione by the capturing of the sulfonyl radical with an alkene moiety. Moreover, the proposed mechanism was supported experimentally and by DFT calculations. A silver‐catalyzed sulfonylation strategy using sulfonamides derived from α‐amino acids is described. The reaction proceeded via decarboxylation, N–S bond cleavage and radical cyclization to provide a variety of coumarins. The reaction was suitable for the synthesis of 2‐oxindoles and an isoquinolinedione by the capturing of the sulfonyl radical with an alkene moiety and cyclization. [ABSTRACT FROM AUTHOR]

A completely regioselective and highly stereoselective palladium‐catalyzed intramolecular hydroarylation of arenesulfonyl ynamines to benzothiazoles was developed. The presence of an electron‐withdrawing group on the triple bond of the sulfonyl ynamine was crucial for the success of the reaction and our mechanistic studies suggest an alkyne‐directed 5‐exo‐dig cyclization pathway. The products easily underwent photoinduced rearrangement to 3‐amino‐1‐benzothiophene‐1,1‐diones (up to 35 % yields after two steps). A completely regioselective and highly stereoselective palladium‐catalyzed intramolecular hydroarylation of arenesulfonyl ynamines to benzothiazoles was developed. Our mechanistic studies suggest an alkyne‐directed 5‐exo‐dig cyclization pathway of the process. The products easily underwent photoinduced rearrangement to 3‐amino‐1‐benzothiophene‐1,1‐diones (up to 35 % yields after two steps). [ABSTRACT FROM AUTHOR]

The oxidative phthalimidoaziridination of conjugated unsaturated N‐sulfonylimines leads, in most cases, to di‐substituted, tri‐substituted and spiro‐fused imidoylaziridines in synthetically useful yields typically above 70 %. The latter are thermally transformed into di‐substituted, tri‐substituted, and condensed N‐sulfonylimidazoles. Interestingly, this ring expansion is accompanied by an intramolecular 1,3‐sulfonyl shift from one nitrogen atom to another. [ABSTRACT FROM AUTHOR]

β-Ketoacyl-ACP-synthase III (FabH) plays an important role in bacterial fatty-acid biosynthesis as an important condensing enzyme. 1,4-Dihydroxy-2-tosylnaphthalene and its analogues are potent inhibitors of FabH. Traditional methods for the synthesis of these compounds still suffer from some drawbacks. In this work, an efficient copper-catalyzed method for the hydroxysulfonylation of quinones with aryl(alkyl)sulfonyl hydrazides was developed for the direct synthesis of 1,4-dihydroxy- 2-phenylsufonylbenzenes. A series of biologically useful FabH inhibitors were obtained in good yields under argon. Both aryl and alkyl substituents were well tolerated in the reaction. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of 3- sec-substituted pyrrole derivatives through vinylogous imine intermediates generated in situ from 2,5-dimethyl-3-[1-(arylsulfonyl)alkyl]pyrroles with high activity and enantioselectivity (up to 98 % ee) was examined. Employing a cinchona alkaloid based chiral bifunctional organocatalyst, the reaction of tritylthiol to sulfonylpyrroles delivered a series of highly enantioselective sulfur-containing 3- sec-substituted pyrroles. [ABSTRACT FROM AUTHOR]

Although the preparation of anomeric glycosylsulfonyl fluoride was unsuccessful, a tetra- O-acetylated C-glucosylpropanesulfonyl fluoride was synthesized starting from the corresponding thioacetate via sulfonate formation as the key intermediate. This sulfonyl fluoride was a bench-stable product that reacted promptly with primary and secondary alkylamines at 80 °C to give the corresponding sulfonamides in good yield. On the other hand, the same fluoride was inert toward arylamines whereas its precursor, the sulfonyl chloride, showed good reactivity. Another limitation of the acetylated sugar sulfonyl fluoride was its lack of reactivity with a multivalent aminated calixarene, this being due to acetyl transfer from the carbohydrate moiety to the amino groups of the scaffold. Fortunately, the tetra- O-benzylated C-glucosylpropanesulfonyl fluoride, prepared by the same reaction sequence employed for the synthesis of the acetylated analogue, reacted with the tetra-aminopropyl-calix[4]arene to afford the corresponding sulfonamide-linked sugar cluster in high isolated yield. A similar approach to the synthesis of calixarene-based iminosugar clusters was unsuccessful because 1-deoxynojirimycin sulfonyl fluoride derivatives could not be generated. However, a tetra-propylsulfonyl fluoride calixarene, obtained from the free-OH calix[4]arene through a three-step reaction sequence, underwent clean coupling with both C-glucosylpropylamine and N-aminopentyl-1-deoxy-deoxynojirimycin derivatives to give the corresponding tetravalent sugar and iminosugar clusters. This metal-free click reaction may constitute a valuable tool in the arsenal of ligation tools for the synthesis of multivalent carbohydrate architectures. [ABSTRACT FROM AUTHOR]

The first utilization of β-nitrostyrenes (readily available by the Henry reaction) for a highly stereoselective, convenient, and catalytic synthesis of (E)-vinyl sulfones at room temperature was investigated. The protocol involves efficient silvercatalyzed denitrative radical cross-coupling of β-nitrostyrenes and sodium sulfinates by using potassium persulfate as an additive to complete the catalytic cycle. [ABSTRACT FROM AUTHOR]

N-sulfonyl imines are widely used as substrates for a range of transformations. Access to N-sulfonyl aldimines is straightforward through direct condensation between the parent aldehyde and the sulfonamide. However, this approach is not efficient for the synthesis of enolizable N-sulfonyl ketimines. Herein we report a rapid and facile methodology for obtaining these products using microwave irradiation. [ABSTRACT FROM AUTHOR]

A new strategy to control the selective Friedel-Crafts reaction of indoles and imines under mild conditions was developed. Phenol derivatives were established as efficient ligands to finely tune the activity of titanocene dichloride. Cp2TiCl2 and phenol catalyzed the mono-Friedel-Crafts reaction of indoles and N-sulfonyl aldimines with good yields (91 %), whereas o-aminophenol significantly enhanced the activity of the titanocene catalyst and promoted the synthesis of bisindole with excellent yields (98 %). The new organometallic Lewis acid catalysts are air-tolerant, can be used with low catalyst loading (3 mmol-%) and are compatible with -NO2, -F, -Cl, -Br, and -OMe (30 examples with yields from good to excellent). The titanocene catalysts were fully characterized by NMR and HRMS analysis. The results suggest that Cp2TiCl(OC6H5) ( I) and Cp2TiCl(OC6H4NH3+Cl-) ( II) were catalytic species for the mono- and double-Friedel-Crafts reactions, respectively. Distinguished from single functional acid catalysts I, catalyst II showed a catalytic cooperative effect of two acid components, which led to a fine tuning of the reactivity as well as to the selectivity of the desired reaction pathways. [ABSTRACT FROM AUTHOR]

Recent remarkable success of copper-catalyzed oxidative bond formations led us to develop an environmentally benign copper-catalyzed sulfur-nitrogen bond-forming reaction to provide synthetically and industrially useful electron-deficient sulfenamides. The low nucleophilicity of N-formyl/acyl- and sulfonylamides was overcome by introducing a 1,5,7-triazabicyclo[4.4.0]dec-5-ene additive. A variety of N-formyl/acylsulfenamides and -thiosulfonamides were synthesized in good yields without over-oxidation of sulfur. Related mechanistic studies supported the proposed reaction mechanism. [ABSTRACT FROM AUTHOR]

Mannich-type reactions of chiral δ-chloro- N- tert-butanesulfinyl-substituted imidates across N-sulfonyl aldimines resulted in the efficient and anti-stereoselective synthesis of new β-(sulfonylamino)- N-sulfinyl imidates ( dr > 99:1). These compounds were then successfully cyclized to give 2-aryl- N-sulfonylpiperidine-3-( N-sulfinyl)carbimidates in high yields. These proved to be useful intermediates for the synthesis of chiral methyl 2-arylpiperidine-3-carboxylates as well as cis-3-amino-2-aryl- N-sulfonylpiperidines. [ABSTRACT FROM AUTHOR]

An efficient enynylation of N-sulfonyl aldimines is described herein. In the presence of Zn-BINOL complexes, catalytic enantioselective addition reactions of terminal 3-en-1-ynes to N-sulfonyl aldimines proceed smoothly to produce enynylated carbinamines in up to 96 % yield and 95 % ee. The adducts are versatile synthetic intermediates that readily undergo Pauson-Khand cycloaddition reactions to give polycyclic products that are otherwise difficult to access. [ABSTRACT FROM AUTHOR]

The solid-phase synthesis of 4 H-benzo[ f][1,2,3]triazolo[1,5- a][1,4]diazepin-6(5 H)-ones and 4,5-dihydrobenzo[ f][1,2,3]triazolo[5,1- d][1,2,5]thiadiazepine 6,6-dioxides under mild and catalyst-free conditions is described. The seven-step synthetic strategy is based on the preparation of polymer-supported 4-nitrobenzenesulfonamides and their alkylation with various propargyl derivatives. Cleavage of the 4-nitrobenzenesulfonyl group from each of the key intermediates was followed by acylation with different 2-azidobenzoic acids, leading to spontaneous intramolecular (Huisgen) 1,3-dipolar cycloaddition. After cleavage from the polymer support, the target compounds were obtained in excellent crude purities and very good overall yields. [ABSTRACT FROM AUTHOR]

Lithium-titanium exchange of tertiary α-sulfonyl carbanions with ClTi(O iPr)3 and Cl2Ti(O iPr)2 in diethyl ether gave bis(1-sulfonylalkyl)titaniums and not the corresponding (1-sulfonylalkyl)titaniums. X-ray crystal structure analysis of di(isopropoxy)bis[1-(phenylsulfonyl)cyclobutyl]titanium and di(isopropoxy)bis[1-(phenylsulfonyl)isopropyl]titanium showed asymmetric distorted octahedral complexes, having hexacoordinate Ti atoms, two C-Ti bonds, four Ti-O bonds, and two four-membered Ti-O-S-Cα rings. According to 1H NMR spectroscopy bis(1-sulfonylcycloalkyl)titaniums are non-fluxional at room temperature. This suggests that chiral bis(1-sulfonylalkyl)titaniums should be configurationally stable. The bis(1-sulfonylalkyl)titaniums are stable at room temperature towards β-H elimination. They selectively add to benzaldehyde in the presence of acetophenone but do not react with methyl iodide. The reaction of tertiary acyclic α-sulfonyl carbanions with ClTi(O iPr)3 in tetrahydrofuran (THF) gives different titanium derivatives with unspecified structures, which not only selectively react with benzaldehyde in the presence of acetophenone but are also alkylated by methyl iodide. [ABSTRACT FROM AUTHOR]

An efficient method for the construction of two distinct Caryl-Caryl bonds through the Ni-catalyzed Suzuki-Miyaura cross-coupling of phenols with arylboronic acids has been developed. This reaction proceeds through the in situ tosylation of phenols by using N, N-ditosylaniline as the sulfonylating reagent, which is highly active, markedly stable, and easily prepared. The scope with respect to the coupling partners - phenols and boronic acids - is broad, and sensitive functional groups are tolerated. Phenols, especially those containing an unprotected amino group, which are generally problematic for coupling under conventional one-pot conditions, are also viable substrates in this transformation. [ABSTRACT FROM AUTHOR]

A direct dehydroxytrifluoromethylthiolation of alcohols with trifluoromethanesulfenamide has been described. This method, based on the original umpolung reactivity of trifluoromethanesulfenamides, proposes a direct 'OH-SCF3 exchange' under mild and, more especially, metal-free conditions. [ABSTRACT FROM AUTHOR]