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The NHC‐catalysed intermolecular Stetter reaction provides direct access to 1,4‐diketones, however current NHC catalysts for this specific transformation remain underdeveloped, significantly limiting the use of this reaction in target‐oriented synthesis. Here we report a novel N‐mesityl thiazolium NHC as a high‐performing catalyst for this reaction, enabling high yields and short reaction times for a range of sterically non‐trivial aliphatic aldehydes reacting with enone substrates. Quantification of the properties of novel and known NHC organocatalysts revealed that both steric and electronic properties play an important role in the success of the new N‐mesityl thiazolium NHC for this reaction. These developments will facilitate wider application of the Stetter reaction as a key carbon‐carbon bond forming reaction for coupling of complex fragments under mild conditions. [ABSTRACT FROM AUTHOR]

The nucleophilic addition of a cyanide anion to a carbonyl group is the basis for several cyanide-catalyzed organic reactions, which are summarized in this review. Since cyanide is also a good leaving group, it is an excellent catalyst for transacylation reactions. As an electron-withdrawing group, it also stabilizes a negative charge in its α-position, thus allowing the umpolung of aldehydes to formyl anion equivalents. The two leading examples are the benzoin condensation and the Michael–Stetter reaction furnishing α-hydroxy ketones and 1,4-dicarbonyl compounds, which are both catalyzed by cyanides. The review also covers variants like the silyl-benzoin coupling, the aldimine coupling and the imino-Stetter reaction. Moreover, some cyanide-catalyzed heterocyclic syntheses are reviewed. 1 Introduction 2 Nucleophilic Additions 2.1 Cyanohydrin Formation 2.2 Corey–Gilman–Ganem and Related Oxidation Reactions 2.3 Conjugate Addition 2.4 Intramolecular Carbocyanation 3 Transacylation Reactions 3.1 Ester Hydrolysis and Transesterification 3.2 Formation of Amides 3.3 Ketones from Esters 3.4 Esters from Ketones 4 Transformations Involving an Umpolung 4.1 Benzoin Condensation 4.2 Aldimine Coupling 4.3 Michael–Stetter Reaction 4.4 Imino-Stetter Reaction 5 Formation of Heterocycles 5.1 Oxazolines from Isocyanoacetates 5.2 Imidazoles from TosMIC via Oxazolines 5.3 Bargellini Reaction 6 Conclusion [ABSTRACT FROM AUTHOR]

Mechanistic studies of the triazolium ion‐catalyzed intramolecular Stetter reaction using initial rates analysis in NEt3/NEt3 ⋅ HCl buffered methanol showed the reaction to be first‐order in catalyst and zero‐order in aldehyde over a broad range of aldehyde concentrations. The observed reaction rate is higher for catalysts bearing N‐aryl substituents with electron‐withdrawing groups. A concurrent, NHC‐independent substrate isomerization was also observed and found to demonstrate a first‐order dependence on aldehyde concentration. The reported data are consistent with deprotonation to form the Breslow intermediate being turnover‐limiting in this process. [ABSTRACT FROM AUTHOR]

The reliable design and prediction of enzyme promiscuity to access transformations not observed in nature remains a long‐standing challenge. Herein, we present the first example of an intramolecular stereoselective Stetter reaction catalyzed by benzaldehyde lyase, guided by the rational structure screening of various ThDP‐dependent enzymes using molecular dynamics (MD) simulations. After optimization, high productivity (up to 99 %) and stereoselectivity (up to 99:1 e.r.) for this novel enzyme function was achieved. [ABSTRACT FROM AUTHOR]

The Stetter reaction is actually a special C−C bond forming reaction through a 1,4‐addition reaction in the presence of nucleophilic catalyst. It involves a reaction between aldehydes and Michael acceptors catalyzed by N‐heterocyclic carbenes (NHC's) leading to preparation of 1,4‐dicarbonyl compounds via carbon‐carbon bond formation. It offers a powerful approach to access 1,4‐dicarbonyl compounds which are significant starting materials and intermediates in the synthesis of several heterocyclic systems, and bioactive heterocyclic framework which are present in natural products. In this review we try to underscore the recent advances in Stetter reaction and its applications from 2015 till date. Notably, we focused on the applications of Stetter reaction in the synthesis of various heterocyclic systems and total synthesis of natural products, which have largely been overlooked, previously. [ABSTRACT FROM AUTHOR]

A facile C(sp2)–H activation of aldehyde under visible‐light conditions using Cu@g‐C3N4 as photocatalyst and water as solvent is reported. The envisaged method involves photocatalytic intermolecular Stetter reaction using differently substituted aldehydes and acrylonitrile to produce various γ‐keto nitriles in good to excellent yield (80–95 %) and 4–10 h at r.t. Operational simplicity, ambient reaction conditions, visible‐light condition, and application of the Cu@g‐C3N4 as photocatalyst make the envisaged protocol an efficient and highly green alternative to the existing methods for synthesis of γ‐keto nitriles. [ABSTRACT FROM AUTHOR]

A highly enantioselective intramolecular NHC‐catalyzed approach for the synthesis of benzo‐fused pyranones bearing quaternary stereocenter is described. The developed methodology is based on annulation reaction between acyl anion intermediates and β,β‐disubstituted Michael acceptors. The reaction offers streamlined and effective access to target products in a highly stereoselective manner. [ABSTRACT FROM AUTHOR]

Thiazolium carbene-catalyzed reactions of 1,2-diketones and 1,2,3-triketones with enones and ynones have been investigated. The diketones gave α,β-double acylation products via unique Breslow intermediates isolable as acid salts, whereas the triketones formed stable adducts with the NHC instead of the coupling products.

The catalytic umpolung of imines remains an underdeveloped approach to reaction discovery. Herein we report an enantioselective aza‐Stetter reaction that proceeds via imine umpolung using N‐heterocyclic carbene catalysis. The reaction proceeds with high levels of enantioselectivity (all ≥96:4 er) and good generality (21 examples). Mechanistic studies are reported and are consistent with turnover‐limiting addition of the NHC to the imine. Poles apart: Imine umpolung is an underdeveloped area of enantioselective catalysis. N‐Heterocyclic carbenes (NHCs) were used to catalyze an enantioselective aza‐Stetter reaction. In contrast to acyl umpolung with NHCs, this reaction requires highly nucleophilic catalysts. The reaction is highly enantioselective (all ≥96:4 er) and accepts various imines and 3‐methylenechroman‐2‐ones. [ABSTRACT FROM AUTHOR]

The valorization of vegetable oil‐derived methyl azelaaldehydate (methyl 9‐oxo‐nonanoate) to monomers was studied through NHC‐catalysed Stetter reaction. Among the Michael acceptors tested, dimethyl fumarate gave the highest selectivity (97 %) for the corresponding Stetter adduct, thus limiting the competing benzoin condensation. Vegetable oil derived methyl azelaaldehydate (methyl 9‐oxo‐nonanoate) was converted to monomers through a NHC‐catalysed Stetter reaction, with limitation of the competing Benzoin condensation. [ABSTRACT FROM AUTHOR]

We report a visible‐light‐mediated organocatalytic strategy for the enantioselective acyl radical conjugate addition to enals, leading to valuable 1,4‐dicarbonyl compounds. The process capitalizes upon the excited‐state reactivity of 4‐acyl‐1,4‐dihydropyridines that, upon visible‐light absorption, can trigger the generation of acyl radicals. By means of a chiral amine catalyst, iminium ion activation of enals ensures a stereoselective radical trap. We also demonstrate how the combination of this acylation process with a second catalyst‐controlled bond‐forming event allows to selectively access the full matrix of all possible stereoisomers of the resulting 2,3‐substituted 1,4‐dicarbonyl products. A 1,4 relation problem: Chiral 1,4‐dicarbonyls are important motifs, but their stereocontrolled synthesis is difficult. A photochemical asymmetric acyl radical addition to enals 2 is presented as one solution to this problem. This enantioselective catalytic strategy is triggered by iminium ion activation. It exploits the visible‐light excitation of 4‐acyl‐1,4‐dihydropyridines 1 to generate acyl radicals under mild conditions. [ABSTRACT FROM AUTHOR]

A bioinspired, intermolecular radical Stetter reaction of α‐keto acids and aldehydes is disclosed that is contingent on a formal "radical umpolung" concept. Enabled by secondary amine activation, electrostatic recognition ensures that the α‐ketocarboxylic acids, which function as latent acyl radicals, are proximal to the in situ generated iminium salts. This photoactive contact ion pair is an electron donor–acceptor (EDA) complex, and undergoes facile single electron transfer (SET) and rapid decarboxylation prior to radical–radical recombination. Importantly, decarbonylation is mitigated by this strategy. The initial computational validation on which the process is predicated matches closely with experiment. Synergising organo‐ and photocatalysis activation principles finally expands the mechanistic and synthetic scope of the classic Stetter reaction to include α,β‐unsaturated aldehydes as acceptors. A bioinspired radical Stetter reaction of α‐keto acids and aldehydes is contingent on a formal "radical umpolung". Electrostatic recognition ensures that the α‐keto carboxylates, which function as latent acyl radicals, are proximal to the iminium ions generated in situ. Synergising organo‐ and photocatalysis activation principles finally expand the mechanistic and synthetic scope of the classic Stetter reaction to include α,β‐unsaturated aldehyde acceptors. [ABSTRACT FROM AUTHOR]

An intermolecular Stetter reaction of aromatic aldehydes with maleimides has been developed using thiazolylidene salt derived Isa‒NHC as an efficient organocatalyst. The synthesized Stetter products “3‒aroylsuccinimides” are important building blocks for the synthesis of natural products and bioactive compounds. The reaction conditions are mild, and various substituents on aromatic aldehyde and maleimide nitrogen were tolerated. [ABSTRACT FROM AUTHOR]

4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl- substituted thiophenes, furans, pyrrols, and piperazines. Key steps are an addition–elimination reaction to ETFBO followed by the thiazolium-catalyzed Stetter reaction. The scope of this chemistry was demonstrated in a new synthetic approach towards the COX-2 selective, nonsteroidal anti-inflammatory drug Celebrex® (celecoxib). [ABSTRACT FROM AUTHOR]

This research is focused on the rational approach to design and synthesis of a novel series of triazole linked pyrrole derivatives through a sequential Paal-Knorr reaction and Click chemistry. These new molecules were screened against Mycobacterium tuberculosis H37Rv and found to display promising anti-mycobacterial activity. Among various compounds, 7g and 7l were identified as leads with minimum inhibitory concentration value 0.78 (μg/mL), which are more effective than standard drugs such as pyrazinamide, ethambutol, and ciprofloxacin and less active than isoniazid and rifampicin. These molecules (minimum inhibitory concentration values <12.5 μg/mL) were also screened against HEK-293T cancer cell lines. Most of these molecules are less toxic but possess higher selectivity index, which indicates the suitability of these compounds for further evaluation. [ABSTRACT FROM AUTHOR]

N-Heterocyclic carbene catalysis allows the rapid formation of functionalized carbon-carbon bonds. Our group has spent the previous decade focusing on broadening practical applications of this type of catalysis. The design and discovery of novel reactivities and catalysts in our group can best be divided into work focusing on the Stetter, ringexpansion, and cross-benzoin reactions. Along with our expansion of the reaction scope, our introduction of novel bis(amino)cyclopropenylidene catalysts for the Stetter reaction successfully suppresses formation of side products, increasing synthetic utility. Concurrent work on ring-expansion reactions allows access to functionalized lactones and lactams. In addition to expanding the scope of the cross-benzoin reaction through use of α-ketoesters and α-amino aldehydes, the introduction of a new triazolylidene catalyst has allowed access to general chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes. 1 Introduction 2 Stetter Reactions 2.1 Domino Stetter Reactions 3 Ring-Expansion Reactions 4 Cross-Benzoin Reactions 5 Summary and Outlook. [ABSTRACT FROM AUTHOR]

We synthesized 2-[2-methyl-5-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-pyrrol-3-yl]-2-oxo-N-(pyridin-4-yl) acetamide 4 as a novel compound derived from the indibulin and combretastatin scaffolds, which are known anti-mitotic agents, using a multistep reaction. We tested its cytotoxic activity against three breast cancer cell lines, namely, MCF-7, T47-D, and MDA-MB 231 as well as normal cell line NIH-3T3, by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The biological activity results showed good cytotoxicity on cancerous cell lines (IC50 value 27.7–39.2 µM) and low toxicity on normal cell line (NIH-3T3, IC50 value > 100 µM).

Recent developments in the N-heterocyclic carbene (NHC)- catalyzed umpolung of aldehydes followed by their interception with activated carbon-carbon double bonds, namely the Stetter reaction, are presented. Advances in the inter- and intramolecular versions of this reaction, enantioselective transformations as well as the use of unactivated olefins in this type of reaction are discussed. 1 Introduction 2 Proposed Mechanism of the Stetter Reaction 3 Intramolecular Stetter Reactions 4 Intermolecular Stetter Reactions 5 Hydroacylation Reactions 6 Applications in Total Synthesis 7 Conclusion [ABSTRACT FROM AUTHOR]

This review summarizes developments in N-heterocyclic carbene-mediated transformation of silicon reagents over the past decade. Several reactions of silicon reagents, including the sila-Stetter reaction, 1,2-addition, carbon–carbon and carbon–oxygen double bond reduction, polymerization, and other miscellaneous reactions, are discussed. The mechanisms of these reactions are also presented. [ABSTRACT FROM AUTHOR]

Methyl 10-undecenoate (2b) has been oxidized with tert-butyl hydroperoxide/selenium dioxide and potassium dichromate to 53% of methyl 9-oxo-10-undecenoate (4). Based on the conversion of 2b, the yield of 4 is 81%. Residual selenium in ester 5 was determined to be less than 1 ppm. The electrophilic double bond in enone 4 reacts in good to excellent yield with a variety of nucleophiles. With dimethyl malonate, acetylacetone, and methyl acetoacetate Michael-adducts at C-11 of enone 4 were obtained in 88-99% yield. Corresponding additions were achieved with nitroethane, 1- and 2-nitropropane in 78- 89% yield. In a Nef-reaction some nitroalkyl adducts were converted to methyl esters of 9,12-dioxofatty acids in 99% yield. In methanol/sodium methoxide the ester methyl 11-methoxy-9-oxoundecanoate was obtained in 86% yield from enone 4. In a three step reaction with ammonium chloride/sodium cyanide, hydrochloric acid/acetic acid, and methanol/2,2-dimethoxypropane the ester 4 yielded 63% of dimethyl 4-oxo-dodecanedioate. With the cyanide ion the electrophilic carbon atom in aldehydes can be converted into a nucleophile (Stetter-reaction). Catalysed by sodium cyanide in DMF aromatic and heteroaromatic aldehydes RCHO with R¼phenyl, 2-thienyl, 2-furyl and 3-pyridyl were added to enone 4 to afford methyl 12-aryl- and methyl 12-heteroaryl-9,12-dioxododecanoates in 54-73% yield. [ABSTRACT FROM AUTHOR]

A novel synthesis of highly substituted pyrrole-N-acetic derivatives is described through the coupling of 1,4-diketones with amino acids following Paal-Knorr's approach. These pyrrole-N-acetic acid derivatives are found to exhibit potent anti-mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis strain H37Rv. In particular, 5n, 5q &5r are found to display excellent anti-mycobacterial activity against M. tuberculosis strain H37Rv with MIC values in the range of 2.97 µM. Conversely, these compounds showed low cytotoxicity (selectivity index: >16.83) against HEK-293T cell line. [ABSTRACT FROM AUTHOR]

Back to BACs: In the pursuit of novel carbene organocatalysts, bis(amino)cyclopropenylidenes (BACs) were explored as alternatives to N‐heterocyclic carbenes. They were effective in catalyzing the Stetter reaction, and displayed unique advantages over the commonly used thiazolylidenes and triazolylidenes. They also mediated extended umpolung reactions of enals. In addition, chiral analogues can be accessed readily for applications in enantioselective catalysis. [ABSTRACT FROM AUTHOR]

After a long history of medical and biochemical investigations of vitamin B1, N-heterocyclic carbenes (NHCs) have recently been used as organocatalysts for a variety of synthetic reactions. This review article highlights the application of NHC-catalyzed reactions including enantioselective reactions to the heterocyclic synthesis. NHC-catalyzed benzoin condensation and Stetter reaction of ether- and amine-linked aldehydes give four- to six-membered oxygen and nitrogen heterocycles. NHC-catalyzed conjugate additions of enals to ketones and imines afford γ-lactones and γ-lactams. When the NHC-catalyzed reaction intermediates of enals are protonated, the reaction of the resulting enols with enones and ene-imines furnish formal hetero-Diels-Alder products. Acyl fluoride and esters can be activated by NHCs, and subsequent aldol and Michael reactions give β-lactones. Oxidation of intermediates derived from enals or the intermediates from ynals provide unsaturated acyl azolium which are transformed into cyclic products via subsequent nucleophilic reactions. NHCs also catalyze [2+2] cycloadditions of ketenes and other heterocumulenes and ring expansion of cyclic aldehydes. [ABSTRACT FROM AUTHOR]

N-Heterocyclic carbene catalyzed desymmetrization of cyclohexadienones to construct tricyclic carbocycles via an intramolecular enantioselective Stetter reaction was realized. With 10 mol% of D-camphor-derived triazolium salt E and 10 mol% of KOAc, various substituted tricyclic carbocycles bearing a quaternary carbon stereogenic center and two contiguous stereocenters were obtained in excellent yields with up to 89% ee. [ABSTRACT FROM AUTHOR]

1,4-Dicarbonyl compounds 2 carrying a phosphonate group were obtained by utilizing a dually N-heterocyclic carbene (NHC) catalyzed domino reaction involving the intramolecular hydroacylation of salicyl alkynylphosphonates 1 and a subsequent intermolecular Stetter reaction with aromatic aldehyde at room temperature. In addition, 2 can also be applied for the synthesis of benzopyranopyrrole carrying a phosphonate group 4 in one pot and in moderate yield. [ABSTRACT FROM AUTHOR]

In the biosynthesis of menaquinone in bacteria, the thiamine diphosphate-dependent enzyme MenD catalyzes the decarboxylative carboligation of α-ketoglutarate and isochorismate to (1R,2S,5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC). The regioisomer of SEPHCHC, namely (1R,5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-2-ene-1-carboxylate (iso-SEPHCHC), has been considered as a possible product, however, its existence has been doubtful due to a spontaneous elimination of pyruvate from SEPHCHC to 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). In this work, the regioisomer iso-SEPHCHC was distinguished from SEPHCHC by liquid chromatography-tandem mass spectrometry. Iso-SEPHCHC was purified and identified by NMR spectroscopy. Just as SEPHCHC remained hidden as a MenD product for more than two decades, its regioisomer iso-SEPHCHC has remained until now., (© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Two exocyclic and endocyclic olefin tautomers of chromone phosphonates were obtained in good to excellent yields at different temperatures by utilizing an N-heterocyclic carbene catalyst in the intramolecular reactions between the formyl group and alkynylphosphonates. The exocyclic olefins can isomerize to the endocyclic derivatives completely when treated with a thiazolium salt precatalyst and potassium carbonate at 30 °C for three to five hours. In addition, the chromone phosphonate derivatives were also applied in the one-pot synthesis of benzopyranopyridine phosphonates in moderated yields. [ABSTRACT FROM AUTHOR]

Abstract: An improved method has been developed for the hydroacylation of enones with aldehydes employing bis-5-(2-hydroxyethyl)-1,3-thiazolium bromide/Et3N system to afford the corresponding 1,4-diketones in good yields. This method is effective for the preparation of 1,4-diketones from both aromatic and aliphatic aldehydes. [Copyright &y& Elsevier]

An efficient method for the synthesis of 4,5-disubstituted 2-aminofuran-3-carbonitriles via a cascade Stetter-γ-ketonitrile cyclization reaction of aromatic aldehydes with acylidenemalononitriles, catalyzed by N-heterocyclic carbenes, has been developed. This procedure provides the corresponding products in moderate to high yields under mild conditions. [ABSTRACT FROM AUTHOR]

new approach has been developed for the synthesis of N-alkylpyrroles with a chiral substituent at the nitrogen atom by the Paal-Knorr reaction using esters of amino acids as the source of chirality. [ABSTRACT FROM AUTHOR]

The diastereoselective synthesis of 2,2-disubstituted-3-hydroxy-indanones was realized by the N-heterocyclic carbene catalyzed [4+1] annulation of phthalaldehyde and 1,2-diactivated Michael acceptors, which involves a tandem process of Stetter reaction, proton shift, and aldol reaction. [ABSTRACT FROM AUTHOR]

Abstract: A series of polyether-substituted triazolium ionic liquids catalysts have been first synthesized for resolving the problem of separation and reuse of Stetter catalysts. The catalysts possess the properties of critical solution temperature (CST) and inverse temperature-dependent solubility in toluene/heptane solvents. Based on these properties, the catalysts can achieve the catalytic process named as thermoregulated phase-separable catalysis (TPSC) with the characteristic of homogeneous reaction at higher temperature and phase-separation at lower temperature. The novel TPSC system has been successfully applied for Stetter reaction of furfural or butanal with ethyl acrylate. The experimental results have showed that the novel catalysts exhibit excellent TPSC with high recycling efficiency. [ABSTRACT FROM AUTHOR]

Abstract: The inversion of the normal reactivity (umpolung) of aldehydes has been induced via N-heterocyclic carbenes (NHCs) thiazol-2-ylidenes 2a or 3a, generated by simple electrolyses of solutions containing thiazolium salt 2 or 3. Accordingly, 1,4-dicarbonyl compounds have been obtained, in mild conditions and in moderate to very high yields, via 1,4-addition of the Breslow intermediates to the suitable Michael acceptor. The procedure has been performed in classical organic solvents (VOCs) as well as in room temperature ionic liquids (RTILs). The different reactivity of aliphatic aldehydes vs the one of aromatic and heteroaromatic aldehydes has been emphasized. [Copyright &y& Elsevier]

The first synthesis of alkylthiazolium-based ionic liquids under ‘green chemistry’ conditions is described. Thiazolium salts and triethylamine have been found to catalyze efficiently the �intramolecular Stetter reaction, giving excellent yields within very short reaction times using solvent-free microwave activation conditions. [ABSTRACT FROM AUTHOR]

This Account chronicles our efforts in the development of the catalytic asymmetric Stetter reaction using chiral triazolium salts as small molecule organic catalysts. Advances in the mechanistically related azolium-catalyzed asymmetric benzoin reaction are discussed, particularly as they apply to catalyst design. A chronological treatise of reaction discovery, catalyst optimization and reactivity extension follows. 1 Introduction 2 Proposed Mechanism of the Benzoin and Stetter Reactions 3 The Benzoin Reaction 4 Synthesis of Chiral Bicyclic Triazolium Salts 4.1 Aminoindanol-Derived Bicyclic Scaffold 4.2 Phenylalanine-Derived Bicyclic Scaffold 5 The Intermolecular Stetter Reaction 6 The Asymmetric Intramolecular Stetter Reaction 6.1 Recent Contributions to the Asymmetric Intramolecular Stetter Reaction 6.2 Comparison of the Asymmetric Intramolecular Stetter �Reaction with Two Different Triazolium Carbene Scaffolds 6.3 Scope of the Intramolecular Stetter Reaction with Different Tethers 6.4 Electronic Effects of the Aromatic Backbone of the Aldehyde on the Intramolecular Stetter Reaction 6.5 Effects of the Michael Acceptor on the Asymmetric Intra-molecular Stetter Reaction 6.6 The Asymmetric Intramolecular Stetter Reaction of Aliphatic Aldehydes 7 Effects of Pre-existing Stereocenters on the Intramolecular Stetter Reaction 8 Synthesis of Quaternary Stereocenters via the Asymmetric Intramolecular Stetter Reaction 9 Synthesis of Contiguous Stereocenters via the Asymmetric Intramolecular Stetter Reaction 10 Asymmetric Synthesis of Hydrobenzofuranones via the Intramolecular Stetter Reaction 11 Applications to Total Synthesis 12 Summary and Outlook [ABSTRACT FROM AUTHOR]

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A convenient three-step route toward a functionalized pyrrole building block for novel anti-inflammatory agents is reported. In contrast to previous strategies, the present approach focuses on inexpensive starting materials and application on a multigram scale. A high degree of functional diversity is demonstrated in various derivatives, and the scope and limitations of this route are discussed. Complementary to the described tetrasubstituted pyrroles, a novel ring-closure protocol based on the Feist-Benary condensation affords trisubstituted analogues. [ABSTRACT FROM AUTHOR]

Abstract: We developed an efficient method for the synthesis of 3-substituted 2,3-dihydroquinolin-4-ones using a one-pot sequential multi-catalytic process: Pd-catalyzed allylic amination–thiazolium salt-catalyzed Stetter reaction cascade. Measurement of the initial rate of the developed sequential process revealed a significant increase in the reaction rate of the Stetter reaction in the presence of Pd(OAc)2 and AcOH·i-Pr2NEt, the constituents of the first Pd catalysis. [Copyright &y& Elsevier]

Abstract: A series of disubstituted cyclopentanones have been synthesized by the intramolecular Stetter reaction. Racemic substrates containing one chiral center were used, allowing us the opportunity to observe a parallel kinetic resolution in the synthesis of 2,3- and 2,4-disubstituted cyclopentanones. The Stetter reaction of 2,5-disubstituted cyclopentanones proved to be substrate controlled, resulting in the selective formation of the cis-diasteromers with low ee. [Copyright &y& Elsevier]

The pressure effect is examined in thiazolium salt catalyzed addition reactions of aldehydes (Stetter reaction and acyloin condensation). Both reactions are not affected by pressure when they involve unhindered substrates. Their response to pressure, however, is strongly enhanced with increasing bulkiness of the reactants. The result is in line with the general pressure effect on sterically congested reactions. [ABSTRACT FROM AUTHOR]

The reaction of arylaldehydes 1 and N,N-dimethylacrylamide in the presence of tributylphosphine afforded N,N-dimethyl-3-aroylpropionamides 2 in moderate yields. The reaction might involve the formation of α-oxo ylide A. [Copyright &y& Elsevier]

Breslow intermediate, Initial rates analysis, NHC, Stetter reaction, Triazolium Keywords: Breslow intermediate; Initial rates analysis; NHC; Stetter reaction; Triazolium EN Breslow intermediate Initial rates analysis NHC Stetter reaction Triazolium 3664 3664 1 07/21/21 20210715 NES 210715 B The Cover Feature b shows collaborative work from the O'Donoghue and Smith groups that describes mechanistic studies of the popular NHC-catalyzed intramolecular Stetter reaction process. Cover Feature: Kinetic and Structure-Activity Studies of the Triazolium Ion- Catalyzed Intramolecular Stetter Reaction (26/2021). [Extracted from the article]

Cyclopropenylidene carbenes have been found to be efficient catalysts for the intermolecular Stetter reaction between aromatic aldehydes and α,β‐unsaturated ketones. In this transformation, the cyclopropenylidene proved superior to more traditional thiazolium‐ and triazolium‐derived carbenes. Preparation and evaluation of a chiral analogue have also been reported. [ABSTRACT FROM AUTHOR]

Abstract: The mechanism of the NHC-catalyzed intermolecular Stetter reaction between benzaldehyde and cyclopropene has been investigated using the PCM-M062X/6-311++G(3df,2p)//M062X/6-31+G(d,p) level of DFT. Compared to the direct reaction, a substantial reduction in the activation free energy by 10.6–14.4kcal/mol is observed when the reaction is performed in the presence of water, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The bases promote the proton transfer step of the reaction to yield the Breslow intermediate. An early concerted transition state has been located for the stereocontrolling C–C bond formation step (ΔG # =26.6kcal/mol) which is used to explain the diastereomeric ratio observed in the experiment. [Copyright &y& Elsevier]