Synthesis Of Thioesters Research Articles

Retraction: One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea.

[This retracts the article DOI: 10.3762/bjoc.11.141.].

Lithio Tris(methylthio)methane as Hydroxy/Thio/Aminocarbonyl Anion Equivalent: Asymmetric Synthesis of α-Amino Acid Esters, Thioesters, Amides, and Peptides.

The use of lithio tris(methylthio)methane as a hydroxy/thio/amino carbonyl anion equivalent in the synthesis of α-amino acids is reported. Addition of the reagent to nonracemic sulfinimines furnished the α-sulfinamido trithioformates in excellent diastereoselectivity. Unmasking the trithioformates to diverse functionalities, such as α-amino acid thioesters, esters, anilides, amides, and di/tri peptides, without epimerization of chiral centers was accomplished.

Beyond Amide Bond Formation: TCFH as a Reagent for Esterification.

In this Communication, an investigation of the combination of N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N-methylimidazole (NMI) for the synthesis of esters and thioesters is described. This work revealed the unique challenges of the reactions of less nucleophilic alcohols and more reactive thiols with the N-acyl imidazolium intermediate and led to the identification of general enabling conditions that provide high yields and selectivity for a range of alcohols and thiols.

Synthesis of fluorine-containing 2-methoxypropanoic and benzoic acids thioesters

Synthesis of fluorine-containing 2-methoxypropanoic and benzoic acids thioesters

Palladium-Catalyzed Thiocarbonylative Synthesis of α,β-Unsaturated Thioesters Using S-Aryl Thioformates as the Thioester Sources.

A palladium-catalyzed thiocarbonylation reaction for the synthesis of α,β-unsaturated thioesters from vinyl triflates with S-aryl thioformates as the thioester sources has been developed. The reaction proceeded smoothly at low temperature, and a variety of α,β-unsaturated thioesters were produced in moderate to high yields with very good functional group tolerance. This protocol features mild reaction conditions, good substrate scope, and avoids the use of toxic CO gas or odorous thiols, which made it a worthy addition to α,β-unsaturated thioester synthesis via a thioester transfer process.

Nickel-catalyzed synthesis of benzyl thioesters and benzyl thioethers: Mono and double decarbonylations/rearrangement of epoxy thioester tandem process

A strategy for Ni-catalyzed decarbonylation and rearrangement of epoxy thioester is described. Mono- and double-decarbonylations were selectively achieved by changing catalytic condition, leading to the production of benzyl-thioesters and benzyl-thioethers in moderate to excellent yields. The new protocol enables a facile route for C–S bond formation in a straightforward fashion.

Rapid Biocatalytic Synthesis of Aromatic Acid CoA Thioesters by Using Microbial Aromatic Acid CoA Ligases.

Chemically labile ester linkages can be introduced into lignin by incorporation of monolignol conjugates, which are synthesized in planta by acyltransferases that use a coenzyme A (CoA) thioester donor and a nucleophilic monolignol alcohol acceptor. The presence of these esters facilitates processing and aids in the valorization of renewable biomass feedstocks. However, the effectiveness of this strategy is potentially limited by the low steady-state levels of aromatic acid thioester donors in plants. As part of an effort to overcome this, aromatic acid CoA ligases involved in microbial aromatic degradation were identified and screened against a broad panel of substituted cinnamic and benzoic acids involved in plant lignification. Functional fingerprinting of this ligase library identified four robust, highly active enzymes capable of facile, rapid, and high-yield synthesis of aromatic acid CoA thioesters under mild aqueous reaction conditions mimicking in planta activity.

How to Build a Metalloenzyme: Lessons from a Protein-Based Model of Acetyl Coenzyme A Synthase

"What I cannot create, I do not understand"─Richard Feynman. This sentiment motivates the entire field of artificial metalloenzymes. Naturally occurring enzymes catalyze reactions with efficiencies, rates, and selectivity that generally cannot be achieved in synthetic systems. Many of these processes represent vital building blocks for a sustainable society, including CO2 conversion, nitrogen fixation, water oxidation, and liquid fuel synthesis. Our inability as chemists to fully reproduce the functionality of naturally occurring enzymes implicates yet-unknown contributors to reactivity. To identify these properties, it is necessary to consider all of the components of naturally occurring metalloenzymes, from the active site metal(s) to large-scale dynamics. In this Account, we describe the holistic development of a metalloprotein-based model that functionally reproduces the acetyl coenzyme A synthase (ACS) enzyme.ACS catalyzes the synthesis of a thioester, acetyl coenzyme A, from gaseous carbon monoxide, a methyl group donated by a cobalt corrinoid protein, and coenzyme A. The active site of ACS contains a bimetallic nickel site coupled to a [4Fe-4S] cluster. This reaction mimics Monsanto's acetic acid synthesis and represents an ancient process for incorporating inorganic carbon into cellular biomass through the primordial Wood-Ljungdahl metabolic pathway. From a sustainability standpoint, the reversible conversion of C1 substrates into an acetyl group and selective downstream transfer to a thiolate nucleophile offer opportunities to expand this reactivity to the anthropogenic synthesis of liquid fuels. However, substantial gaps in our understanding of the ACS catalytic mechanism coupled with the enzyme's oxygen sensitivity and general instability have limited these applications. It is our hope that development of an artificial metalloenzyme that carries out ACS-like reactions will advance our mechanistic understanding and enable synthesis of robust compounds with the capacity for similar reactivity.To construct this model, we first focused on the catalytic proximal nickel (NiP) site, which has a single metal center bound by three bridging cysteine residues in a "Y"-shaped arrangement. With an initial emphasis on reproducing the general structure of a low-coordinate metal binding site, the type I cupredoxin, azurin, was selected as the protein scaffold, and a nickel center was incorporated into the mononuclear site. Using numerous spectroscopic and computational techniques, including electron paramagnetic resonance (EPR) spectroscopy, nickel-substituted azurin was shown to have similar electronic and geometric structures to the NiP center in ACS. A substrate access channel was installed, and both carbon monoxide and a methyl group were shown to bind individually to the reduced NiI center. The elusive EPR-active S = 1/2 Ni-CH3 species, which has never been detected in native ACS, was observed in the azurin-based model, establishing the capacity of a biological NiI species to support two-electron organometallic reactions. Pulsed EPR studies on the S = 1/2 Ni-CH3 species in azurin suggested a noncanonical electronic structure with an inverted ligand field, which was proposed to prevent irreversible site degradation. This model azurin protein was ultimately shown to perform carbon-carbon and carbon-sulfur bond formation using sequential, ordered substrate addition for selective, stoichiometric thioester synthesis. X-ray spectroscopic methods were used to provide characterization of the remaining catalytic intermediates, resolving some debate over key mechanistic details.The overall approach and strategies that we employed for the successful construction of a functional protein-based model of ACS are described in this Account. We anticipate that these principles can be adapted across diverse metalloenzyme classes, providing essential mechanistic details and guiding the development of next-generation, functional artificial metalloenzymes.

Retraction Note to: Synthesis of thioesters and thioamides under solvothermal condition using thiourea as thionating agent

Retraction Note to: Synthesis of thioesters and thioamides under solvothermal condition using thiourea as thionating agent

Isothiouronium-Mediated Conversion of Carboxylic Acids to Cyanomethyl Thioesters.

We report the development of an isothiouronium salt as a reagent for the operationally simple synthesis of cyanomethyl thioesters with high functional group tolerance and avoiding the use of thiols. Additionally, we show that the products can be engaged in amide synthesis in either a two-step or one-pot fashion.

Direct Synthesis of Thioesters from Feedstock Chemicals and Elemental Sulfur.

The development of a mild, atom- and step-economical catalytic strategy that effectively generates value-added molecules directly from readily available commodity chemicals is a central goal of organic synthesis. In this context, the thiol-ene click chemistry for carbon-sulfur (C-S) bond construction has found widespread applications in the synthesis of pharmaceuticals and functional materials. In contrast, the selective carbonyl thiyl radical addition to carbon-carbon multiple bonds remains underdeveloped. Herein, we report a carbonyl thiyl radical-based thioester synthesis through three-component coupling from feedstock aldehydes, alkenes, or alkynes and elemental sulfur by direct photocatalyzed hydrogen atom transfer. This method represents an orthogonal strategy to the conventional thiol-based nucleophilic substitution and exhibits a remarkably broad substrate scope ranging from simple commodity chemicals such as ethylene and acetylene to complex pharmaceutical molecules. This protocol can be easily extended to the synthesis of thiolactones, oligomer/polymers, and thioacids. Its synthetic utility has been demonstrated by a two-step synthesis of the drug esonarimod. Mechanistic studies indicate that the use of elemental sulfur to trap acyl radicals is both thermodynamically and kinetically favored, illustrating its great potential for the synthesis of sulfur-containing molecules.

Synthesis of Thioesters from Aldehydes via N-Heterocyclic Carbene (NHC) Catalyzed Radical Relay.

We have developed an efficient N-heterocyclic carbene (NHC)-catalyzed thioesterification of aldehydes using N-thiosuccinimides as the thiolation reagent. This organocatalyzed transition involves the generation of sulfur radicals by single electron transfer of the Breslow enolate (generated from aldehyde and NHC catalyst) with N-thiosuccinimides. This method offers facile access to various highly functionalized thioesters and exhibits good chemical yields and functional group tolerance.

Martina Letizia Contente

Martina Letizia Contente

In situ generation of acyloxyphosphoniums for mild and efficient synthesis of thioesters.

We present a novel approach for in situ generation of acyloxyphosphoniums by premixing iodobenzene dicarboxylates and triphenylphosphine, resulting in efficient thioester synthesis (up to 100% yield). Stable solid iodobenzene dicarboxylates, achieved via carboxylate exchange, serve as hypervalent iodine precursors. The resulting acyloxyphosphoniums allow convenient one-pot thioester synthesis under mild conditions. Our method demonstrates facile acyloxyphosphonium production from iodobenzene dicarboxylates and Ph3P, enabling diverse thioester preparation. ESI-MS analysis confirms acyloxyphosphonium ion formation, pivotal in acylation. This strategy holds potential for combinatorial thioester synthesis and broader nucleophile modification applications.

Palladium-catalyzed convenient synthesis of thioesters from carboxylic acids and disulfides

A novel palladium-catalyzed convenient synthesis of thioesters from various carboxylic acids and disulfides has been developed.

Electrochemical Decarboxylation Coupling of α-Keto Acids with Thiophenols: A New Avenue for the Synthesis of Thioesters

Electrochemical Decarboxylation Coupling of <i>α</i>-Keto Acids with Thiophenols: A New Avenue for the Synthesis of Thioesters

Synthesis and structural features of indium(III) furan-2-thiocarboxylates showing efficient catalytic activity toward multicomponent reactions via Knoevenagel condensation.

A series of furan-2-thiocarboxylate complexes of indium(III), Et3NH[In(SCOf)4] (1), iPr2NH2[In(SCOf)4] (2), [In(2,2'-bipy)(SCOf)3] (3a), and [In(1,10-phen)(SCOf)3] (3b), have been synthesized and structurally characterized. Complex 4, [In(TMEDA)(SCOf)(SH)2], was obtained by the partial hydrolysis of [In(TMEDA)(SCOf)3] (3). Heterobimetallic complexes [(SCOf)2In(μ-SCOf)2Cu(PPh3)2] (5) and [(SCOf)2In(μ-SCOf)2Ag(PPh3)2] (6), were also synthesized and characterized. In an attempt to synthesize the binary compound, In(SCOf)3 (7), a thioester fCOSCH2SCOf (8) was obtained serendipitously; thus, a novel convenient approach for thioester synthesis is introduced. The catalytic activities of all the complexes were assessed for Knoevenagel condensation and Knoevenagel initiated MCRs for the synthesis of chromene and imidazopyrimidine derivatives and it was found that complex 2 is a very efficient catalyst (much superior to the previously reported ones).

Synthetic Strategies for Versatile Thioester Building Blocks

AbstractThioester constitutes a fundamentally unique intermediate, engaged in various biosynthesis processes in living systems as well as a versatile synthon in modern organic synthesis. Transition metal catalysis and radical reaction manifolds have enabled to enrich the repertoire of synthetic methods for thioesters. In this review, we have accommodated the recent reports on modern strategies towards thioester synthesis from a plethora of readily available feedstocks, such as alkenes, alkynes, alcohols, phenols or commodity chemicals/synthetic building blocks like organic aldehydes, halides or organoboron reagents under various catalysis domains. Furthermore, the momentous advancements of employing progenitors of odorous thiols as well as CO‐surrogates have contextually been emphasized, alongside the utilization of native free thiols and CO gas.

Palladium-Catalyzed Thiocarbonylation of Aryl Iodides with S-Aryl Thioformates via Thioester Transfer.

Herein we reported a novel approach to synthesize thioesters with S-aryl thioformates as thioester sources. The reaction proceeded at ambient temperature using widely available starting ingredients, wherein the thioester moiety was smoothly transferred to aryl iodides from S-aryl thioformates. A variety of substrates with various electronic natures were all tolerated under the reaction conditions to furnish desirable thioesters in ranges from moderate to excellent yields. The gram-scale reaction was also conducted, and there was virtually little change in chemical yield, indicating that large-scale synthesis of thioesters may be viable using this method.

N-Thiohydroxy Succinimide Esters (NTSEs): Versatile Reagents for Selective Acyl and Acylthio Transfer.

Differentiation between similarly reactive sites in molecules represents an ongoing challenge of organic synthesis. Herein we described one kind of versatile reagents, N-thiohydroxy succinimide esters (NTSEs), serving as both acyl and acylthio surrogates for the diverse synthesis of ketones, thioesters, amides, and acyl disulfides by selective cleavage of similarly reactive C-S and N-S bonds.