Alkyl Sulfonyl Chlorides Research Articles

Nickel-Catalyzed Cyclization/Thiocarbonylation of Alkene-Tethered indoles with sulfonyl Chlorides: Synthesis of Thioester-Substituted Indolo[2,1-a]isoquinolines

A novel and straightforward procedure for the synthesis of thioester-substituted indolo[2,1-a]isoquinolines has been established. The reaction proceed via nickel-catalyzed cyclization/thiocarbonylation from alkene-tethered indoles and sulfonyl chlorides. Very good compatibility toward a wide range of functional groups was observed, both aryl and alkyl sulfonyl chlorides were well tolerated. With Mo(CO)6 as a convenient and solid CO surrogate, and by using sulfonyl chloride as an abundant and cheap sulfur source, a variety of thioester-substituted indolo[2,1-a]isoquinolines were obtained in moderate to high yields.

Synthesis of thioester-functionalized 2H-benzopyrans through palladium-catalyzed one-pot cyclization/thiocarbonylation using sulfonyl chlorides as the sulfur sources

A general and efficient protocol for the synthesis of thioesters-functionalized 2H-benzopyrans has been developed through a palladium-catalyzed one-pot cyclization/thiocarbonylation reaction of propargyl ethers with sulfonyl chlorides as promising and easily accessible sulfur sources. The reaction showed good compatibility towards versatile functional groups, both aryl and alkylsulfonyl chlorides were well tolerated. Without any external reductant, using Mo(CO)6 as a convenient CO source, a wide range of 2H-benzopyrans bearing thioester as an attractive functional group were obtained in moderate to good yields.

Thiourea/NCBSI/HCl System: Telescoping alkyl halide to alkyl sulfonyl chloride by recyclable N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI)

A convenient and efficient method to synthesize diverse alkyl sulfonyl chlorides through N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI)-mediated oxidative chlorosulfonation of S-alkyl isothiouronium salts obtained from alkyl chlorides is presented. Synthesizing structurally diverse alkyl sulfonyl chloride in moderate to excellent yields up to 98% from alkyl halide via easy formation of S-alkyl isothiouronium salts using inexpensive thiourea. The mild reaction conditions and broad substrate scope make this method beneficial and advantageous to alkylsulfonyl chloride syntheses.

(2S)-2-(Difluoro(methoxy)methyl)pyrrolidine-1-sulfinyl fluoride as a new reagent in the Cl/F exchange reactions with aryl and alkyl sulfonyl chlorides

The reaction of (2S)-2-(difluoro(methoxy)methyl)pyrrolidine-1-sulfinyl fluoride with aryl, heteryl and alkyl sulfonyl chlorides provides a convenient synthetic route to sulfonyl fluorides. DFT calculations predict negative reaction energy values for the exchange reaction. The S-F bond energy is higher in the sulfonyl fluorides than that in sulfinyl fluorides.

Oxidant-Assisted Sulfonylation/Cyclization Cascade Synthesis of Alkylsulfonylated Oxindoles via the Insertion of SO2.

An oxidant-assisted tandem sulfonylation/cyclization of electron-deficient alkenes with 4-alkyl-substituted Hantzsch esters and Na2S2O5 for the preparation of 3-alkylsulfonylated oxindoles under mild conditions in the absence of a photocatalyst and transition metal catalyst is established. The mechanism studies show that the alkyl radicals, which come from the cleavage of the C-C bond in 4-substituted Hantzsch esters under oxidant conditions, subsequently undergo the in situ insertion of sulfur dioxide to generate the crucial alkylsulfonyl radical intermediates. This three-component reaction provides an efficient and facile route for the construction of alkylsulfonylated oxindoles and avoids the use of highly toxic alkylsulfonyl chlorides or alkylsulfonyl hydrazines as alkylsulfonyl sources.

Visible-light-promoted cyclization of 3-indolylallylamides enabling synthesis of tetrahydrocarbolinones

A novel visible-light promoted radical cyclization reaction of 3-indolylallylamides with sulfonyl chlorides as coupling partners has been described, which provides a unique approach toward the synthesis of functionalized tetrahydrocarbolinones. This reaction involves the reduction of sulfonyl chlorides to sulfonyl radicals, addition of sulfonyl radicals to alkenyl moiety, and following cycloaddition to indolyl at the C2 position. This photocatalytic reaction tolerates a broad range of aryl and alkyl sulfonyl chlorides with diverse functional groups, which provides a direct and operationally simple protocol to construct functionalized tetrahydrocarbolinones.

Promoting Catalytic C-Selective Sulfonylation of Cyclopropanols against Conventional O-Sulfonylation Using Readily Available Sulfonyl Chlorides.

Against the backdrop of the well-known O-sulfonylation of cyclopropyl alcohols with sulfonyl chlorides, we examined the feasibility of conducting regioselective C-sulfonylation. By emulating an umpolung strategy-guided design, we report for the first time the Cu(II)-catalyzed β-sulfonylation of cyclopropanols by a mechanism that potentially involves an oxidative addition of a sulfonyl radical to a metal homoenolate. Unlike reported methods, this protocol allows a practical synthetic route to γ-keto sulfone building blocks from cyclopropanols by leveraging commercially available aryl- and alkyl-sulfonyl chlorides, common reagents in organic chemistry laboratories. Using operationally simple open-flask conditions, the preparative scope of starting materials was demonstrated using an array of aryl- and alkyl-substituted sulfonyl chlorides and cyclopropanols (43 examples, up to 96% yield).

Photoredox-Catalyzed Radical-Radical Cross-Coupling of Sulfonyl Chlorides with Trifluoroborate Salts.

Sulfones are widely found in natural products and drug molecules. Here, we disclose a strategy for direct synthesis of sulfone compounds with diverse structures by visible-light-catalyzed radical-radical cross-coupling of sulfonyl chlorides and trifluoroborate salts. Allyl, benzyl, vinyl, and aryl trifluoroborates can be successfully cross-coupled with (hetero)aryl and alkyl sulfonyl chlorides, respectively. This strategy features redox neutrality, good substrate generality, simple operation, and benign reaction conditions.

Discovery of Resveratrol and its Derivatives as Novel Antiviral and Anti- Phytopathogenic-Fungus Agents.

Plant diseases caused by viruses and pathogens have posed a serious threat to global agricultural production and are difficult to control. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. The natural product resveratrol was found to have good antiviral activity against the tobacco mosaic virus (TMV) and fungicidal activities against 14 kinds of phytopathogenic fungi. The aim of this work was to design, synthesize a series of derivatives of resveratrol, and evaluate their antiviral and fungicidal activities systematically. Novel resveratrol sulfonate derivatives were prepared by a convenient synthesis method from resveratrol, alkyl sulfonyl chloride, aryl sulfonyl chloride, and heterocyclic sulfonyl chloride. Their structures were also identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). Most of the targets were obtained at a high yield. Compounds I-2, I-5, I-10, II-2, and II-4, with excellent antiviral activities, showed higher anti-TMV activities than those of lead compounds and commercial ribavirin (inhibitory rates of 38, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). In particular, compounds I-5, I-10, II-2, and II-4 displayed similar inhibitory effects as ningnanmycin (inhibitory rates of 54, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, thereby emerging as new antiviral pilot compounds. Further fungicidal activity tests showed that resveratrol derivatives also displayed broad-spectrum fungicidal activities. The anti-TMV activities of these compounds were discovered for the first time. Some of these simply structured compounds showed higher TMV inhibitory effects than ribavirin. The current study provided valuable insights into the antiviral and fungicidal activities of resveratrol derivatives, but more modification of the structure should be conducted.

Convenient Synthesis of Thioester‐Substituted Oxindoles by Palladium‐Catalyzed Thiocarbonylative Cyclization with Sulfonyl Chlorides as the Sulfur Source

Comprehensive SummaryA general and straightforward strategy for the synthesis of thioester‐substituted oxindoles via a palladium‐catalyzed thiocarbonylative cyclization process has been developed. With sulfonyl chlorides as promising sulfur source, a wide range of thioester‐substituted oxindoles were obtained in moderate to high yields. Both aryl and alkyl sulfonyl chlorides were well tolerated, and Mo(CO)6 played a dual role as both a CO source and a reductant in this approach.

Photoredox and Copper‐Catalyzed Sulfonylphosphorothiolation of Alkenes toward β‐Sulfonyl Phosphorothioates

AbstractA photoredox and copper‐catalyzed sulfonylphosphorothiolation of alkenes has been developed. With the use of readily available aryl or alkyl sulfonyl chlorides as radical precursors and (RO)2P(O)SH as coupling partners, a wide range of decorated β‐sulfonyl phosphorothioates could be obtained in 37–98% yields with good functional group tolerance. Importantly, this three‐component reaction can be conveniently extended to late‐stage modification of bioactive molecules and gram‐scale synthesis.magnified image

Synthesis of Aryl Methyl Sulfides from Arysulfonyl Chlorides with Dimethyl Carbonate as the Solvent and C1 Source

AbstractA new procedure for the synthesis of aryl methyl sulfides from dimethyl carbonate (DMC) and arylsulfonyl chlorides has been achieved. In this strategy, DMC plays a dual role as both, C1 building block and green solvent. Arylsulfonyl chlorides served as the sulfur precursors, and a variety of aryl methyl sulfides were obtained in moderate to excellent yields with good functional group tolerance. Additionally, alkylsulfonyl chloride and dibenzyl carbonate are proven to be suitable substrates as well.

One-pot synthesis of imidazo[1,2-α]pyridine thioethers using imidazo[1,2-α]pyridines, arylsulfonyl chlorides and hydrazine

A one-pot reaction of making RS-substituted imidazo[1,2-α]pyridine derivatives by directly using aryl or alkylsulfonyl chloride and hydrazine was developed, selectively giving good yields of the expected products. Compared with previously reported methods of using ArSO2NHNH2 as a sulfur source, this method is much cheaper, more practical and convenient and enriches current methods to make thioether-containing compounds, providing a good example of green chemistry.

Unusual C–H Bond Activation and C(sp3)–C(sp3) Bond Formation at an Fe(II) Bis(amide) Carbene Complex

Treatment of (IMes)Fe(NTMS2)2 with 4 equiv of methanesulfonyl chloride (MsCl = MeSO2Cl) resulted in a complex reaction sequence involving substitution of two TMS groups for Ms, followed by the unexpected C(sp3)–H bond activation of Ms and subsequent C(sp3)–C(sp3) bond formation to generate the bimetallic Fe complex, [IMesH]2[Cl2Fe(N(TMS)SO2(CH2)2SO2N(TMS))2FeCl2] (1) (IMes = 1,3-bis(2,4,6-trimethylphenyl)-imidazole-2-ylidene; TMS = SiMe3). Extending this C–H activation/C–C bond-forming chemistry to larger alkylsulfonyl chloride chains (i.e., Et and Bu) similarly resulted in C–C coupling, but with decreased chemoselectivity. Detailed mechanistic studies, including using possible intermediate model compounds, were performed in order to elucidate a unifying mechanism for this previously unknown avenue to C(sp3)–C(sp3) bond formation.

Ammonium Iodide-Mediated Sulfenylation of 4-Hydroxycoumarins or 4-Hydroxyquinolinones with a Sulfonyl Chloride as a Sulfur Source

A novel ammonium iodide-induced sulfenylation of 4-hydroxycoumarins or 4-hydroxyquinolinones by using an aryl- or alkylsulfonyl chloride as the sulfur source gave a wide range of 3-sulfanyl-4-hydroxycoumarins or 3-sulfanyl-4-hydroxyquinolinones, respectively, in moderate to good yields. This method provides as a simple approach to the direct formation of C–S bonds, which is of high value and utility in the pharmaceutical industry.

ChemInform Abstract: Aminoxidation of Arenethiols to N‐Chloro‐N‐sulfonyl Sulfinamides.

AbstractAlkanethiols are converted into the corresponding alkylsulfonyl chlorides under these conditions.

ChemInform Abstract: Metal‐ and Base‐Free Syntheses of Aryl/Alkylthioindoles by the Iodine‐Induced Reductive Coupling of Aryl/Alkyl Sulfonyl Chlorides with Indoles.

An Iodine-catalysed 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 participated in the sulfenylation of C(sp2)–H bonds, resulting in a high to excellent yield of indole 3-sulfenylether molecules. It is noteworthy that indole-3-thiomethyl ether is efficiently generated with methanesulfonyl chloride as an electrophile, indicating the potential of this methodology.

Palladium-catalyzed alkenyl C–H bond sulfonylation reaction using organosulfonyl chlorides

A Pd-catalyzed alkenyl C–H bond direct sulfonylation of vinyl pyridine and enamides was developed. Various arylsulfonyl chlorides were tested in this reaction and the desired products were obtained in good yields. Moreover, the alkyl sulfonyl chloride could also be used though the yield was lower. A possible Pd(II)/Pd(IV) catalytic pathway involved in this coupling reaction was proposed.

Development of an Extremely Efficient Oxidative Chlorination Reaction: The Value of Routine Data Collection

This contribution describes the development of an extremely efficient process for the oxidative chlorination of a benzyl, alkyl thioether to yield an alkylsulfonyl chloride. This process was subseq...

Catalytic Asymmetric Synthesis of β‐Sultams as Precursors for Taurine Derivatives

Beta-sultams, biologically interesting sulfonyl analogues of beta-lactams, have been prepared by an organocatalytic asymmetric formal [2+2]-cycloaddition approach of non-nucleophilic imines with alkyl sulfonyl chlorides. In the case of very electron poor N-tosyl imines derived from chloral or ethylglyoxylate, this reaction type was catalyzed by cinchona alkaloids providing the heterocycles in high yield, with good diastereoselectivity and up to 94% ee. Mechanistic investigations suggested that the product formation proceeded via a zwitterionic imine-catalyst adduct. The scope was significantly extended by 2-pyridylsulfonyl imines derived from non-activated aromatic aldehydes employing Yb(OTf)3 as Lewis acid cocatalyst. The synthetic value of the strained enantioenriched beta-sultams was demonstrated by smooth nucleophilic ring opening reactions with O-, N- and C-nucleophiles yielding a variety of acyclic beta-aminosulfonyl (taurine) derivatives (sulfonates, sulfonamides, sulfones) without racemization or epimerization.