Sulfur Surrogate Research Articles

KSCN‐mediated one‐pot thiocyanation tandem cyclization of enaminones: a facile access to 2‐amino/imino thiazolo fused chromone and coumarin frameworks

A rapid metal‐free approach describing one‐pot thiocyanation of chromone and coumarin enabling tandem cyclization via potassium thiocyanate as a sulfur surrogate was unveiled. Interestingly, this enaminone‐mediated protocol facilitated straightforward access to medicinally significant 2‐amino/imino thiazolo fused chromone and coumarin frameworks. This methodology provided good atom‐economy, remarkable functional group tolerance, and scalability. Alongside establishing a wide substrate scope, it also provided a feasible scalability up to gram scale.

Mechanochemical Nickel-Catalyzed Carbon-Sulfur Bond Formation between Aryl Iodides and Aromatic Sulfur Surrogates.

The formation of aromatic thioethers from C-S coupling is of great importance in synthetic chemistry. Traditional solution strategies through transition-metal catalysis generally require bulk solution, heat, and longer reaction time. Herein, a mechano-promoted sulfenylation of aryl iodides with nickel catalysis is described. The active aromatic sulfide agents are in-situ generated from aromatic thiol or disulfide and subsequently adapted in the nickel catalytic cycle, with a tolerance of broad substituted groups under optimized conditions. In addition to the gram-scale synthesis that reveals the application potential of the method, the radical trapping and competitive experiments are also conducted for the mechanistic study, thus providing a plausible mechanism rationally. Furthermore, the proposed methodology is certificated as being versatile and following the green principles with ideal calculated values of green chemistry metrics, and the comparison with other approaches for C-S bond formation is also demonstrated.

Nickel-catalyzed desulfonative cross-coupling of benzylsulfonyl chlorides with arylsulfonyl chlorides for synthesis of asymmetric thioethers

C–S bond formation is of great interest and plays an important role in organic synthesis, material science, and medicinal chemistry. On the other hand, sulfonyl chlorides are inexpensive, readily available, and easily handled reagents. The use of two different types of sulfonyl chlorides to prepare unsymmetrical thioethers has been considered a challenge task. Here, a nickel-catalyzed desulfonative cross-coupling reaction for the synthesis of unsymmetrical thioethers is disclosed. In this reaction, benzylsulfonyl chlorides play a role as the electrophiles, and arylsulfonyl chlorides serve as the sulfur precursors. We demonstrate that arylsulfonyl chlorides reductively couple with electrophilic benzylsulfonyl chlorides through a desulfonylation process, giving a variety of asymmetric thioethers in moderate-to-excellent yields with good functional group tolerance. By employing readily available sulfonyl chlorides as both electrophiles and sulfur surrogates, we address a challenge in organic synthesis.

Cu-Catalyzed and iodine mediated synthesis of thioaurones via in situ C-S bond generation using xanthate as a sulfur surrogate.

An efficient method for synthesizing thioaurones has been developed using xanthate as an odorless sulfur surrogate. This reaction's key success lies in the use of iodine as a reagent, which promotes the α-iodination followed by cyclization of saturated ketones. This methodology has also been demonstrated with less reactive 2'-bromochalcones in good yield. Synthesis of the red isomer of indigo, i.e. a thia-analog of indirubin, was also achieved.

The journey of C–S bond formation from metal catalysis to electrocatalysis

This perspective describes the journey of C–S bond constructions starting from transition metal catalysis through oxidant catalysis, photocatalysis and very recently employed electrocatalysis by using various sulfur surrogates.

Acid-Mediated Sulfonylthiolation of Arenes via Selective Activation of SS-Morpholino Dithiosulfonate.

A trifluoroacetic-acid-mediated desulfurilative sulfonylthiolation of arenes using SS-morpholino dithiosulfonate is described. This system is based on selective activation of the morpholino group over the tosyl group of the doubly transformable sulfur surrogate. Mechanistic studies suggested that the reaction proceeds through electrophilic aromatic substitution followed by sulfur extrusion. The wide substrate scope of this reaction and the transformability of the resulting thiosulfonates enable expeditious access to divergent multifunctionalized sulfides.

Metal-catalyzed C-S bond formation using sulfur surrogates.

Sulfur-containing compounds are present in a wide range of biologically important natural products, drugs, catalysts, and ligands and they have wide applications in material chemistry. Transition metal-catalyzed C-S bond-forming reactions have successfully overcome the obstacles associated with traditional organosulfur compound syntheses such as stoichiometric use of metal-catalysts, catalyst-poisoning and harsh reaction conditions. One of the key demands in metal-catalyzed C-S bond-forming reactions is the use of an appropriate sulfur source due to its odor and availability. The unpleasant odor of many organic sulfur sources might be one of the reasons for the metal-catalyzed C-S bond-forming reactions being less explored compared to other metal-catalyzed C-heteroatom bond-forming reactions. Hence, employing an appropriate sulfur surrogate in the synthesis of organosulfur compounds in metal-catalyzed reactions is still of prime interest for chemists. This review explores the recent advances in C-S bond formation using transition metal-catalyzed cross-coupling reactions and C-H bond functionalization using diverse and commercially available sulfur surrogates. Based on the different transition metal-catalysts, this review has been divided into three major classes namely (1) palladium-catalyzed C-S bond formation, (2) copper-catalyzed C-S bond formation, and (3) other metal-catalyzed C-S bond formation. This review is further arranged based on the different sulfur surrogates. Also, this review provides an insight into the growing opportunities in the construction of complex organosulfur scaffolds covering natural product synthesis and functional materials.

Copper-catalyzed domino synthesis of multi-substituted benzo[b]thiophene through radical cyclization using xanthate as a sulfur surrogate.

The Cu-catalyzed domino synthesis of multi-substituted benzo[b]thiophene through radical cyclization of 2-iodophenyl ketones was developed using xanthate as a sulfur surrogate. This method was extended to obtain tetracyclic Lupinalbin analogues through double C-S/C-O bond formation by changing the substituents. The products were converted to a HTI photoswitch, benzothiophene-fused flavone.

Metal-free C-S coupling of thiols and disulfides.

In organic synthesis, transition-metal and photoredox-catalysis-based reaction systems are emerging trends for the construction of C-S bonds. Many review articles have recently appeared in this field; however, we present herein an overview of metal-free C-S coupling reactions using thiols or disulfides as sulfur surrogates. The oxidants we have considered include peroxides, tert-butyl nitrite (TBN), DDQ, iodine reagents, and molecular oxygen. In addition, selective electrochemical oxidative transformations are also covered with mechanistic details.

Copper-catalyzed double C-S bond formation for the synthesis of 2-acyldihydrobenzo[b]thiophenes and 2-acylbenzo[b]thiophenes.

An efficient domino process is developed for the synthesis of diversely substituted 2,3-dihydrobenzo[b]thiophenes from 2-iodoketones using a Cu-catalyst and easily available xanthate as a sulfur surrogate in good yields. This domino method has been expanded for the synthesis of 2-acylbenzo[b]thiophenes using in situ generated iodine (I2) from by-product KI in high yields. Treatment of xanthate with the copper(ii)-catalyst reduced it to a Cu(i)-catalyst, which initiates the catalytic cycle. A possible mechanism has been proposed based on the results from XPS-analysis, an iodine color test and several other control experiments.

Domino Synthesis of Thioflavones and Thioflavothiones by Regioselective Ring Opening of Donor-Acceptor Cyclopropane Using In-Situ-Generated Thiolate Anions.

A copper-catalyzed intramolecular ring opening of donor-acceptor cyclopropane is developed for the synthesis of 3-alkyl-carbonated thioflavones and further extended to 3-alkyl-carbonated thioflavothione, using xanthate as a sulfur surrogate. This reaction proceeds through thiolate formation/ring opening/Krapcho decarboxylation, followed by hydrogen abstraction, to give thioflavanone, which is further oxidized by in-situ-generated iodine from waste byproduct KI. Experimental studies prove that the charge-transfer complex is responsible for the conversion of thioketone to ketone.

Bunte Salts and Congeners as Efficient Sulfur Surrogates: Recent Advances

Bunte Salts and Congeners as Efficient Sulfur Surrogates: Recent Advances

CuI catalyzed-novel one-pot synthesis of aryl alkenyl thioethers through Ullmann-type coupling reactions using carbon disulfide as a sulfur surrogate in the presence of nitroalkanes and aryl iodides

A mild, general and efficient copper-catalyzed system for C-S bond formation is developed. With CuI as catalyst and l-Proline as ligand, the S-arylation of nitroalkane-CS2 adducts with aryl iodides were performed under mild conditions to give the corresponding products in good to excellent yields.

One-pot synthesis of thioesters with sodium thiosulfate as a sulfur surrogate under transition metal-free conditions.

In this paper, we report an efficient synthetic method for thioester formation from sodium thiosulfate pentahydrate, organic halides, and aryl anhydrides. In the one-pot two-step reactions developed in this study, sodium thiosulfate was used as the sulfur surrogate for acylation with anhydrides, followed by substitution with organic halides through the in situ generation of thioaroylate. Furthermore, two important organic compounds could be successfully synthesized using our developed method. The advantages of the one-pot two-step reactions are operational simplicity, structurally diverse products with 42%-90% yields, use of relatively low toxic and odourless reagents, and easy applicability to large-scale operation.

Domino Synthesis of Thiochromenes through Cu-Catalyzed Incorporation of Sulfur Using Xanthate Surrogate.

An efficient domino reaction has been developed for the synthesis of thiochromenes through Cu-catalyzed in situ incorporation of sulfur. This domino method avoids the use of less accessible and unpleasant arenethiols as starting materials, instead utilizes very stable aryl halides along with potassium ethyl xanthate as an odorless sulfur surrogate. The domino methodology proceeds through C(aryl)-S coupling, thioester cleavage, sulfa-Michael addition, aldol reaction, and elimination reaction sequences to provide thiochromenes in good yields.

An isocyanide based multi-component reaction under catalyst- and solvent-free conditions for the synthesis of unsymmetrical thioureas

A new and efficient method for the synthesis of thiourea derivatives by a sequential one-pot, three-component reaction between aromatic isocyanides, amines, and 1,2-di-tert-butyldisulfane (DTBS) was developed and 27 different examples were synthesized in good to excellent yields. DTBS was identified as an effective sulfur surrogate without the use of both catalysts and solvents. This protocol does not employ any transition metal catalyst or special experimental setup.

ChemInform Abstract: Fe—Cu Catalyzed Synthesis of Symmetrical and Unsymmetrical Diaryl Thioethers Using 1,3‐Benzoxazole‐2‐thiol as a Sulfur Surrogate.

An efficient Fe–Cu catalyzed approach is herein developed using 1,3-benzoxazole-2-thiol as a thiol surrogate for the synthesis of symmetrical and unsymmetrical diaryl thioethers. This method provides an odorless and inexpensive strategy which can be applied to various aryl and nitrogen containing aryl halides in moderate to excellent yields up to 90%.

Fe–Cu catalyzed synthesis of symmetrical and unsymmetrical diaryl thioethers using 1,3-benzoxazole-2-thiol as a sulfur surrogate

An efficient Fe–Cu catalyzed approach is herein developed using 1,3-benzoxazole-2-thiol as a thiol surrogate for the synthesis of symmetrical and unsymmetrical diaryl thioethers.

ChemInform Abstract: Dithiooxamide as an Effective Sulfur Surrogate for Odorless High‐Yielding Carbon—Sulfur Bond Formation in Wet PEG200 as an Eco‐Friendly, Safe, and Recoverable Solvent.

In this study, we have employed dithiooxamide, a solid, odorless, and commercially available compound, as a sulfur surrogate for the preparation of dialkyl sulfides from available alkyl halides in high yields. This sulfur transfer agent was also used for a copper-catalyzed high-yielding preparation of diaryl sulfides from their available aryl halides and for the preparation of thia-Michael adducts in high yields. All the reactions were performed under odorless conditions in wet PEG200 (PEG = polyethylene glycol), which is an eco-friendly, safe, and recoverable solvent. The protocols were easily applicable to large-scale operation.

ChemInform Abstract: A Metal‐Free and Recyclable Synthesis of Benzothiazoles Using Thiourea as a Sulfur Surrogate.

AbstractTreatment of substrates (I) with thiourea and TFA gives benzothiazoles (IV) and TFA salts (V).