Regioselective Thiolation Research Articles

Lewis Acid‐Promoted C−H Chalcogenation of Arenes and Heteroarenes

AbstractAn efficient catalytic system employing TMS•OTf for the regioselective thiolation of electron‐rich arenes with sulfonyl hydrazides has been developed. The reaction occurs in a solvent mixture of dichloroethane and trifluoroethanol under mild conditions, with the addition of water. This method furnishes a range of para‐thio‐substituted arenes and 3‐sulfenyl‐indoles in good to excellent yields, marking a significant advancement in organic synthesis.

Regioselective Thiolation of Indoles with Sulfinyl Amides

AbstractA mild, efficient and highly regioselective thiolation of indoles by sulfinyl amides via direct C−H functionalization is described. Sulfinyl amides could be reduced to thioethers and submitted as the thiolation reagents were developed. This reaction provides a useful method for the synthesis of 3‐indole thioethers and 2,3‐dithioindole derivatives. This mix‐and‐go approach also tolerates broad substrate scope and outstanding functional group compatibility. In addition, this preparation could be easily conducted on a gram scale with high efficiency.

Metal‐Free Regioselective 1,6‐Conjugate Addition of Sulfide to para‐Quinone Methides: Simple Access to E‐Selective Thiaoxacyclophanes

AbstractWe realized a simple approach involving the 1,6‐conjugate addition (regioselective thiolation) of para‐quinone methides (p‐QMs) with easily available thio‐based nucleophiles. Through ring‐closing metathesis (RCM), this procedure delivered a variety of para‐ and meta‐thiaoxacyclophanes as E‐isomers in good yields. A simple thiol‐free one‐pot approach is reported for the direct synthesis of sulfides and sulfones under green reaction conditions without the use of any metal catalysts. Low‐cost and easily accessible compounds such as p‐QMs and benzyl bromides are used as starting materials in the presence of potassium thioacetate (PTA) and Oxone®. Novel thiaoxacyclophanes were assembled in three simple steps including conjugate addition of PTA, Grignard addition, and RCM sequence.

Regioselective synthesis of (Z)-alkenyl thioethers via Rh(III)-catalyzed thiolation of N-2,6-difluoroaryl acrylamides

Rh(III)-catalyzed regioselective thiolation of acrylamides with disulfides using weakly coordinating N-2,6-difluoroaryl acrylamides as directing groups has been developed. This transformation provides a robust protocol for the preparation of different (Z)-alkenyl thioethers, with favorable features such as high regioselectivity and good functional group tolerance. Moreover, synthetic value is further demonstrated by gram-scale reaction and conversion of product.

Nickel-Catalyzed Regioselective Thiolation of Anilides with Thiols

AbstractAn efficient method for direct thiolation of anilides with thiols using NiCl2·6H2O as the catalyst is developed. Using this method, the desired products were successfully synthesized in moderate to good yields. Initial mechanistic studies suggest that this reaction proceeds through a radical pathway.

Gold‐Catalyzed Reactions of 2‐Alkynyl‐1‐indolyl‐1,2‐diols with Thiols: Stereoselective Synthesis of (Z)‐α‐Indol‐3‐yl α‐(2‐Thioalkenyl) Ketones

AbstractPropargylic glycols, 2‐alkynyl‐1‐(indol‐3‐yl)‐1,2‐diols, react with thiols undergoing a complex but selective gold‐catalyzed transformation that gives rise to α‐indol‐3‐yl α‐((Z)‐2‐thioalkenyl) ketones. The sequence is triggered by the regioselective thiolation of indolyl diols followed by an attack of the sulfur instead of the indole over the activated alkyne. The final compounds are obtained in remarkably high yields and arise from simple starting materials such as indolyl acyloins, ethynyl magnesium bromide and thiols.magnified image

Direct C-H Thiolation for Selective Cross-Coupling of Arenes with Thiophenols via Aerobic Visible-Light Catalysis.

An aerobic metal-free, visible-light-induced regioselective thiolation of phenols with thiophenols is reported. The cross-coupling protocol exhibits great functional group tolerance and high regioselectivity. Mechanistic studies reveal that the disulfide radical cation plays a crucial role in the visible-light catalysis of aerobic thiolation. Simply controlling the equivalent ratio of substrates enables the selective formation of sulfide or sulfoxide products with high activity in a one-pot reaction.

Metal-Free, Acid/Phosphine-Induced Regioselective Thiolation of p-Quinone Methides with Sodium Aryl/Alkyl Sulfinates.

A simple and efficient method for the regioselective thiolation of p-quinone methides with sodium aryl/alkyl sulfinates has been established using an acid/phosphine-induced radical route under transition-metal-free conditions. A broad range of sodium aryl/alkyl sulfinates and p-quinone methides (p-QMs) are compatible for the reaction, giving the expected products with good to excellent yields. Control experiments were also performed to gain insights into the generation mechanism of thiyl radicals and hydrogen-atom transfer process. This protocol provides a safe and feasible way for the formation of carbon-sulfur bonds.

Thiol Activation toward Selective Thiolation of Aromatic C-H Bond.

Direct C-S bond coupling is an attractive way to construct aryl sulfur ether, a building block for a variety of biological active molecules. Herein, we disclose an effective model for regioselective thiolation of the aromatic C-H bond by thiol activation instead of arene activation. Strikingly, this method has been applied into anisole derivatives that are not available in the arene activation approach to forge a single thioether isomer with high reactivity.

Temperature-controlled regioselective thiolation of 2-indolylmethanols under aqueous micellar conditions

Micelle-assisted, temperature-enabled regiodivergent thiolation of 2-indolylmethanols in water under mild conditions.

Metal-free direct regioselective thiolation of imidazoheterocycles in water at room temperature

A metal-free direct thiolation of imidazoheterocycles with various thiophenol in water at room temperature has been developed. In addition, the chemistry provides several advantages including mild condition, high yields, good functional group tolerance, green solvents and suitable for large-scale operations.

Metal- and base-free regioselective thiolation of the methyl C(sp3)–H bond in 2-picoline N-oxides

Metal- and base-free thiolation of the unactivated methyl C(sp3)–H bond in 2-picoline N-oxides with thiols is achieved by a one-pot, two-step sequence, including a TFAA-mediated [3,3]-sigmatropic rearrangement of pyridine N-oxides and TBAB-catalyzed direct conversion of trifluoroacetates into thioethers.

Regioselective thiolation of electron rich arenes and heterocycles in recyclable catalytic media

A convenient and novel approach has been developed for the synthesis of unsymmetrical diaryl sulfides by the reaction of sulfonyl hydrazides with phenols, aromatic amines and heterocycles using a [Bmim][Br] ionic liquid through C–S bonds formation.

ChemInform Abstract: Iodine‐Catalyzed Regioselective Thiolation of Flavonoids Using Sulfonyl Hydrazides as Sulfenylation Reagents.

AbstractRegioselective aryl and alkyl thiolation reactions of flavonoid derivatives are described which proceed in position C‐8 for C‐5 hydroxylated flavone, flavonol, dihydroflavone, and isoflavones derivatives, or in position 7 in case of C‐4 hydroxylated aurone derivatives.

ChemInform Abstract: Palladium N‐Heterocyclic Carbene Catalyzed Regioselective Thiolation of 1‐Aryl‐3‐methyl‐1H‐pyrazol‐5(4H)‐ones Using Aryl Thiols.

Abstract A palladium N-heterocyclic carbene [Pd(NHC)Cl2] complex of Vitamin B1 developed earlier in our lab was also found to be an effective catalyst for regioselective thiolation via C–H bond activation of 1-aryl-3-methyl-1H-pyrazol-5(4H)-ones 1a–c using aryl thiols 2a–e. The protocol was found to be simple, efficient and highly regioselective to afford the target products 3a–o in good to excellent yields.

(Invited) Regioselective Thiolation of Perchlorinated Graphene

Chemical and physical properties of graphenes are naturally determined by its edge structures. Chemical functionalization is one of promising strategy to modulate the peripheral structure of graphenes. As a molecular-level model system, large polycyclic aromatic hydrocarbons (PAHs), i.e. so-called nanographenes, can be chemically modified through edge functionalization. Although the synthetic protocols for edge substitution of nanographenes are well developed, the regioselective chemical functionalization of nanographenes remains an enormous challenge, most likely due to the lack of suitable synthetic protocols. Here we show a regioselective peripheral thiolation of nanographenes by selective thiolation of perchlorinated nanographene. Based on two model perchlorinated nanographenes C42Cl18 and C60Cl24, we found the chlorines at the vertex of nanographenes are regioselectively substituted by the thiophene-2-thiol, which shows the first case of selective functionalization of nanographenes. The rest chlorines at the bay positions provide the platform for further functionalization. It enables us to design and produce a series of edge functionalized nanographenes. Figure 1. Regioselective thiolation of perchorinated graphene Figure 1

Palladium N-heterocyclic carbene catalyzed regioselective thiolation of 1-aryl-3-methyl-1H-pyrazol-5(4H)-ones using aryl thiols

A palladium N-heterocyclic carbene [Pd(NHC)Cl2] complex of Vitamin B1 developed earlier in our lab was also found to be an effective catalyst for regioselective thiolation via C–H bond activation of 1-aryl-3-methyl-1H-pyrazol-5(4H)-ones 1a–c using aryl thiols 2a–e. The protocol was found to be simple, efficient and highly regioselective to afford the target products 3a–o in good to excellent yields.

Iodine-catalysed regioselective thiolation of flavonoids using sulfonyl hydrazides as sulfenylation reagents.

Iodine-catalysed regioselective sulfenylation of flavonoid derivatives with sulfonyl hydrazides was developed. Various flavonoid thioethers were obtained in moderate to good yield. The thiolation could be conveniently directed to C-8 for flavone, flavonol, dihydroflavone, and isoflavone derivatives or to C-7 for aurone derivatives by employing the isopropyl ethers of flavonoids bearing free OH groups at the C-5 or C-4 positions.

ChemInform Abstract: Iodine‐Catalyzed Regioselective Thiolation of Imidazo[1,2‐a]pyridines Using Sulfonyl Hydrazides as a Thiol Surrogate.

Iodine-catalyzed regioselective sulfenylation of imidazo[1,2-a]pyridines via C(sp2)–H bond functionalization has been achieved using sulfonyl hydrazides as a thiol surrogate. A library of 3-sulfanylimidazopyridines with broad functionalities was synthesized under metal and oxidant-free practical reaction conditions. This methodology is also applicable for the regioselective sulfenylation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole.

ChemInform Abstract: Regioselective Thiolation of Arenes and Heteroarenes: C—H Functionalization Strategy for C—S Bond Formation.

A facile transition-metal-free oxidative cross-dehydrogenative coupling reaction involving selective formation of a C-S bond leading to the synthesis of arylthiobenzoxazoles, heteroarylthiobenzoxazoles, and arylthiobenzothiazoles has been described. This highly regioselective C-H functionalization reaction with electron-rich aromatic systems including heteroaromatics is achieved by reversing the reactivity of sulfur in the presence of a suitable oxidant and strong acid.