Synthesis Of Thioethers Research Articles

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Simple reaction, useful chemistry. The electron donor‐acceptor complex (EDA) photochemistry provides a simple and efficient platform for organic synthesis. A general EDA complex strategy formed by readily accessible thiophenolate anion and oxime ester successfully realizes the diverse synthesis of thioethers under visible light irradiation. Such a strategy could also enable a thiol‐catalysis for the synthesis of phenanthridines. More details are discussed in the article by Zhong et al. on pages 2751—2756. image

A General Electron Donor‐Acceptor Photoactivation Using Oxime Esters Enabled Divergent Thioetherifications†

Comprehensive SummaryThe EDA complex‐mediated reactions involving oxime esters have been few studied. Herein, an EDA complex formed by thiophenolate anion and oxime ester is reported for photoinduced divergent synthesis of thioethers, depending on different types of oxime esters. Operational simplicity, mild reaction conditions, and flexible options of leaving group demonstrate the generality and synthetic utility of this approach. Such an approach can also enable an interesting thiol‐catalysis for the synthesis of phenanthridines.

The Reaction of Aryl Thiols or Thioureas with o‐Diiodoarenes/NaH to Access o‐Iodoaryl Thioethers

AbstractHerein we report a method for the synthesis of thioethers by forging C(aryl)‐S bond via an aryne mechanism. The active aryne species can be generated from o‐diiodoarenes and NaH in THF at room temperature, then lead to the arylations of a wide range of aryl thiols and thioureas. Different from transition metal‐catalyzed cross‐coupling reactions, no disubstituted byproduct is formed in our protocol. The o‐iodoaryl thioether products are intermediates that could be transformed into pharmaceutically interesting molecules.

Photochemical Organocatalytic Synthesis of Thioethers from Aryl Chlorides and Alcohols.

Thioethers, often found in pharmaceuticals and natural compounds, typically involve metal cross-coupling reactions, high temperatures, and the use of disagreeable thiols for their synthesis. Here we present a straightforward, thiol-free organocatalytic protocol that uses mild conditions to stitch together inexpensive alcohols and aryl chlorides, yielding a diverse array of aryl alkyl thioethers. Central to this approach was the discovery that tetramethylthiourea can serve as a simple sulfur source upon intercepting photochemically generated aryl radicals. To form radicals, we used a readily available indole thiolate organocatalyst that, when excited with 405 nm light, gained a strongly reducing power, enabling the activation of typically unreactive aryl chlorides via single-electron transfer. Radical trapping by the thiourea, followed by an alcohol attack via a polar path, resulted in the formation of thioether products.

Pd(OAc)2/Xantphos Catalyzed Reductive Coupling of Sulfonyl Chlorides: Synthesis of Thioethers by Sulphur Dioxide Extrusion

AbstractHerein, we reported a successful cross coupling of aryl sulfonyl chlorides to forge thioether skeleton via Pd catalysis. This transformation proceeded in the presence of Xantphos. Preliminary mechanism studies demonstrated dual roles of Xantphos: (i) a reductant that reduced sulfonyl radical to thio radical; (ii) a ligand that promotes coupling reactions.

Carbon−Sulfur Coupling Reactions Catalyzed by Nickel(II) N‐Heterocyclic Carbene Complexes

AbstractThe synthesis and characterization of Nickel(II) complexes with novel pincer‐type N‐heterocyclic carbene complexes were investigated. Nickel(II)‐NHC complexes, 7 and 8, were characterized using HR ESI‐MS, IR, UV‐Visible, and elemental analysis. The complex 7 with less sterically demanding pincer ligand was investigated in the catalytic one pot synthesis of thioethers via coupling reactions of a series of aryl and alkyl halides in the presence of thiourea. In a mixture of water and ethanol, 5 mol% of 7 catalyzed the C−S bond coupling reaction in high yields.

Copper-Catalyzed Direct Thiolation of Ketones Using Sulfonohydrazides: A Synthetic Route to Benzylic Thioethers.

A facile copper-catalyzed sustainable thiolation of ketones with sulfonohydrazides has been designed for the efficient construction of benzylic thioethers in excellent yield under mild reaction conditions. The current approach avoids the widely used thiolation reagent, thiols. The commercial availability of the base and reagents, broad substrate scope, and convenient reaction procedure make it an attractive method for benzylic thioether synthesis.

Synthesis and Functionalization of Thiophosphonium Salts: A Divergent Approach to Access Thioether, Thioester, and Dithioester Derivatives.

Herein, we report a straightforward practical method for efficiently obtaining a diverse range of thiophosphonium salts. This method involves the direct coupling of commercially available thiols and aldehydes with Ph3P and TfOH. The setup is simple and carried out in a metal-free manner. The synthetic utility of these salts is demonstrated through various examples of C-P bond functionalizations, enabling the synthesis of thioether, deuterated thioether, thioester, and dithioester derivatives. These products, which serve as valuable building blocks, are obtained in high yields.

Multiplexed Assessment of Promiscuous Non-Canonical Amino Acid Synthase Activity in a Pyridoxal Phosphate-Dependent Protein Family.

Pyridoxal phosphate (PLP)-dependent enzymes afford access to a variety of non-canonical amino acids (ncAAs), which are premier buildings blocks for the construction of complex bioactive molecules. The vinylglycine ketimine (VGK) subfamily of PLP-dependent enzymes plays a critical role in sulfur metabolism and is home to a growing set of secondary metabolic enzymes that synthesize γ-substituted ncAAs. Identification of VGK enzymes for biocatalysis faces a distinct challenge because the subfamily contains both desirable synthases as well as lyases that break down ncAAs. Some enzymes have both activities, which may contribute to pervasive mis-annotation. To navigate this complex functional landscape, we used a substrate multiplexed screening approach to rapidly measure the substrate promiscuity of 40 homologs in the VGK subfamily. We found that enzymes involved in transsulfuration are less likely to have promiscuous activities and often possess undesirable lyase activity. Enzymes from direct sulfuration and secondary metabolism generally had a high degree of substrate promiscuity. From this cohort, we identified an exemplary γ-synthase from Caldicellulosiruptor hydrothermalis (CahyGS). This enzyme is thermostable and has high expression (~400 mg protein per L culture), enabling preparative scale synthesis of thioether containing ncAAs. When assayed with l-allylglycine, CahyGS catalyzes a stereoselective γ-addition reaction to afford access to a unique set of γ-methyl branched ncAAs. We determined high-resolution crystal structures of this enzyme that define an open-close transition associated with ligand binding and set the stage for future engineering within this enzyme subfamily.

Visible‐Light‐Induced Synthesis of Thioethers through Three‐Component Reactions of α‐Diazoesters, Thiols, and Cyclic Ethers

AbstractThioethers are important sulfur‐containing compounds that have widespread application in organic synthesis, medicinal chemistry and materials science. Herein, a visible‐light‐mediated three‐component reaction of α‐diazoester, thiol, and cyclic ether leading to thioether has been developed at room temperature. Through this methodology, a variety of three‐component coupling products with the introduction of the ring‐opening of ether could be efficiently assembled under photocatalyst‐ and additive‐free conditions.

Theoretical understanding of mechanochemical (ball-milling) synthesis of thioethers: a CDFT approach

Theoretical understanding of mechanochemical (ball-milling) synthesis of thioethers: a CDFT approach

Synthesis of Thioethers via Ni-Catalyzed Cross-Coupling of Alkyl Thiols with Aryl or Alkenyl Triflates

Synthesis of Thioethers via Ni-Catalyzed Cross-Coupling of Alkyl Thiols with Aryl or Alkenyl Triflates

Palladium- and nickel-catalyzed synthesis of thioethers via thioesters – Aryl halides coupling

Palladium- and nickel-catalyzed synthesis of thioethers via thioesters – Aryl halides coupling

Nonbasic Synthesis of Thioethers via Nickel-Catalyzed Reductive Thiolation Utilizing NBS-Like N-Thioimides as Electrophilic Sulfur Donors.

The nonbasic synthesis of unsymmetrical thioethers via nickel-catalyzed reductive thiolation between aryl(hetero) iodides and N-thioimides is illustrated. N-Bromosuccinimide (NBS)-like N-thioimides were found quite reactive toward thiolation with carbon electrophiles, and a series of structurally varied thioethers were successfully prepared under mild reaction conditions. The transformation was featured with the new application of the NBS-like reagents, good functional group tolerance, and late-stage modification of biologically active scaffolds, thus providing an expeditious and efficient platform to construct polyfunctional thioethers.

One-pot synthesis of thioethers from indoles and p-quinone methides using thiourea as a sulfur source.

Thiourea is an inexpensive and user friendly sulfur reagent that acts as a sulfur source. A simple and efficient protocol has been developed to access thioethers by reacting indoles with p-quinone methides using thiourea as the sulfur source. In our experiments, the reaction apparently proceeded through an S-(3-indolyl)isothiuronium iodide intermediate and subsequent generation of indolethiol that attacked the 1,6 position of p-quinone methides to give desired thioethers in good to excellent yields.

Transition Metal CatalysedC‐SCross‐Coupling Reactions at Room Temperature.

AbstractTransition metal catalysed formation ofCsp2‐Sbond through cross‐coupling reaction stands important and powerful tools in synthetic organic chemistry. The reaction constitutes an important strategy for the synthesis of thioethers that possess diverse biological activities in medicine and agriculture. Nonetheless, maintaining reaction temperature duringCsp2‐Scross‐coupling reaction decides fate of desired product along with possibility of by‐product and disulfides. The economy of process, safety and environmental issue demands thioether synthesis at mild condition and room temperature. Only very few reactions were successful under mild condition using Pd, Cu, Ni, Ni−Ir and Ir catalyst. The current prospective summarizes the best protocols used for efficientCsp2‐Scross‐coupling reactions by transition metal catalyst under mild condition.

Recent Metal-Catalyzed Methods for Thioether Synthesis

AbstractThis review summarizes the more recent methods (since 2015) for the synthesis of thioethers using homogeneous metals as catalysts. The thioether moiety can be found in numerous compounds for pharmaceutical, agricultural, or material applications and it is therefore important to develop new, efficient methods for their synthesis. The recent efforts in this field focus on the use of non-precious metal catalysts, as well as on the development of new bond-forming processes.1 Introduction2 Cross-Couplings3 C–H Activation4 Hydrothiolation5 Carbothiolation6 Miscellaneous7 Conclusion

Sulfonyl Chlorides as Thiol Surrogates for Carbon-Sulfur Bond Formation: One-Pot Synthesis of Thioethers and Thioesters.

A method to synthesize thioethers and thioesters directly from readily available sulfonyl chlorides is reported. We demonstrate that a transient intermediate formed during phosphine-mediated deoxygenation of sulfonyl chlorides can be trapped in situ by activated alcohols or carboxylic acids to effect carbon-sulfur bond formation. The method is operationally simple and tolerates a broad range of functional groups. Special attention has been focused on the late-stage diversification of densely functionalized natural products and pharmaceuticals.

Potassium phosphate catalyzed highly efficient synthesis of structurally diverse thioethers at ambient temperature

Commercially available potassium phosphate has been demonstrated to be a highly efficient catalyst for the synthesis of thioethers employing two different routes viz. alkylation of thiols with alkyl/aralkyl halides and by Michael addition of thiols to conjugated alkenes.

Catalyst‐Free Synthesis of Thioethers through C−N Bond Cleavage of Aminonaphthol/Aminophenol Derivatives

AbstractReadily available aminonaphthol/aminophenol derivatives were converted to the corresponding thioethers under catalyst‐free reaction conditions. Environmentally benign aqueous medium was utilized for the transformation of aminonaphthol derivatives to the corresponding thioethers under aerobic reaction conditions. Saturated brine solution was identified as a suitable medium for the synthesis of thioethers from aminophenol derivatives. Control experiments revealed that the nature of leaving group and reaction atmosphere plays a vital role in determining the yield of the products.