Thiazolium-mediated multicomponent reactions: a facile synthesis of 3-aminofuran derivatives

[reaction: see text] A facile synthesis of highly functionalized 3-aminofuran derivatives by the multicomponent reactions of thiazolium salts, aldehydes, and DMAD is described.     

The Chemistry of Stable Carbenes. Part 2. Benzoin-type condensations of formaldehyde catalyzed by stable carbenes

Stable carbenes derived from thiazole, 1H-imidazole, and 4H-1,2,4-triazole are efficient catalysts for benzointype condensations of formaldehyde. Catalysts derived from N-substituted thiazolium salts trimerize formaldehyde to dihydroxyacetone ( II ). Catalysts based on 1,4-disubstituted 4H-1,2,4-triazol-1-ium salts give glycolaldehyde ( I ) as the main product and no II , whereas N,N′-disubstituted 1H-imidazol-3-ium salts yield mixtures of both products. The isolation of several intermediates in the catalytic cycle provide a better insight into the reaction mechanism.     

Cyanosilylation of aldehydes catalyzed by N-heterocyclic carbenes

N-Heterocyclic carbenes produced in situ from salts of imidazolium, benzimidazolium, pyrido[1,2-c]imidazolium, imidazolinium, thiazolium, and triazolium catalyze the addition of trimethylsilylcyanide to aldehydes to yield cyanohydrin trimethylsilyl ethers. The use of C₂-symmetric imidazolidenyl carbene derived from (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium chloride led to enantioselective cyanosilylation.     

Thiazolocyanines

Quaternary thiazolium salts with active methylthio groups and 2-thiazolyl and 2-pyridyl residues attached to the nitrogen atom of the thiazole ring were obtained. 2-Methyl-3-(2-pyridyl)-and 2-methyl-3-(2-thiazolyl)thiazolium salts were synthesized by replacement of the methylthio group by a methyl group. Monomethylidynecyanines and nullmethylidyne- and dimethylidynemerocyanines were obtained from salts with active methyl and methylthio groups.See [1] for communication XV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 749–752, June, 1973.     

Thiazolium-catalyzed additions of acylsilanes: a general strategy for acyl anion addition reactions

A strategy utilizing N-heterocyclic carbenes (NHCs) derived from thiazolium salts has been developed for the generation of carbonyl anions from acylsilanes. Synthetically useful 1,4-diketones and N-phosphinoyl-alpha-aminoketones have been prepared in good to excellent yields via NHC-catalyzed additions of acylsilanes to the corresponding alpha,beta-unsaturated systems and N-phosphinoylimines. These organocatalytic reactions are air- and water-tolerant methods to execute robust carbonyl anion addition reactions. Additionally, polysubstituted aromatic furans and pyrroles have been efficiently synthesized in a one-pot process using this carbonyl anion methodology. The addition of alcohols to the reaction renders the process catalytic in thiazolium salt. In an effort to synthesize a potential intermediate along the proposed reaction pathway, silylated thiazolium carbinols have been identified to provide good yields of carbonyl anion addition products when subjected to the standard reaction conditions in the presence of suitable electrophiles.     

Catalytic additions of acylsilanes to imines: an acyl anion strategy for the direct synthesis of alpha-amino ketones

The addition of acylsilanes to imines catalyzed by neutral carbenes (or zwitterions) generated in situ from readily available thiazolium salts is described. The general reaction successfully utilizes acylsilanes as carbonyl anion precursors and is tolerant of a range of structural diversity on the acylsilane or imine electrophile. The overall reaction utilizes easily available precursors and directly accesses protected alpha-amino ketones in the correct oxidation state.     

Oxidative addition of 2-substituted azolium salts to Group-10 metal zero complexes--a DFT study

Generation of N-heterocyclic carbene (NHC) complexes [(dmpe)M(azol-2-ylidene)R] via the oxidative addition of a series of 2-substituted azolium salts to Group-10 zerovalent metal complexes has been investigated using density functional theory (2-R = H, Me, Ph; Azole = imidazole, thiazole, oxazole; M = Ni, Pd, Pt). Overall, platinum-based pathways result in the greatest enthalpies of reaction, but due to the reactive nature of Group-10 metals bearing the 1,2-bis(dimethylphosphino)ethane (dmpe) chelate, nickel and palladium species also have little trouble proceeding to stable products in the absence of a significant barrier. Imidazolium salts were found to be the most vulnerable to oxidative addition due to their low stabilisation energies when compared to the oxazolium and thiazolium species. Activation barriers show the general trend of phenyl > methyl > hydrido with regard to the azole 2-substituent, with no observed barrier for all but one of the 2-hydrido cases. Minimal barriers were found to exist in a number of cases for activation of a C(2)-CH3 bond suggesting that synthesis of alkyl-carbene complexes may be possible via this route under certain conditions, and therefore ionic liquids based on these substituted azolium salts may be active participants in catalytic reactions.     

Direct amination of homoenolates catalyzed by N-heterocyclic carbenes

N-Heterocyclic carbenes derived from N-mesityl-N-methyltriazolium salts are effective catalysts for generating homoenolate species from alpha,beta-unsaturated aldehydes. The unique intermediate adds to the electrophilic nitrogen of 1-acyl-2-aryldiazenes, and the resulting activated carbonyl unit undergoes an intramolecular acylation event. This formal [3+2] cycloaddition between alpha,beta-unsaturated aldehydes and acylaryldiazenes, catalyzed by an N-heterocyclic carbene, produces substituted pyrazolidinones in good yields. This new NHC-catalyzed reaction accommodates aromatic and alkyl alpha,beta-unsaturated aldehydes and various aromatic diazenes. A chiral triazolium salt catalyzes the formation of the pyrazolidinone product in moderate yield and good enantioselectivity. The pyrazolidinones can undergo reductive N-N bond cleavage to give beta-amino acid derivatives.     

Synthese und Eigenschaften von 2-(α-Hydroxyalkyl)-und 2-(α-alkoxycarbonyl)-substituierten 4-Methyl-5-(β-hydroxyäthyl)-thiazolen und -thiazoliumsalzen

Condensation of the tetrahydropyranyl ether of the α-hydroxyalkyl-thioamides with 3-bromo-4-hydroxy-2-pentanones yields DL -2-(α-hydroxyalkyl)-4-methyl-5-(β-hydroxyethyl)-thiazoles. By oxidation with chromic anhydride 2-hydroxymethyl-4-methyl-5-(β-acetoxyethyl)-thiazole yields the corresponding 2-formyl derivative. The latter compound reacted with GRIGNARD complexes gives the homologous DL -2-(α-hydroxyalkyl)-4-methyl-5-(β-hydroxyethyl)-thiazoles. This is a general method for the synthesis of the thiazole part of the «active aldehydes». 2-Acetyl-4-methyl-5-(β-hydroxyethyl)-thiazole is also obtained by chromic oxidation of the suitable methylthiazol-2-yl-carbinol. The condensation of the thioamides obtained from the α-ethoxycarbonyl-nitriles with 3-bromo-5-acetoxy-2-pentanone results in the DL -2-(α-ethoxycarbonyl-alkyl)-4-methyl-5-(β-acetoxyethyl)-thiazoles. The α-hydroxyl function is introduced into the 2-(α-ethoxycarbonyl-alkyl) group by chlorination with sulfuryl chloride and replacement of the introduced chlorine by acetate. The latter compounds are the esters of the thiazole part of the «active α-oxo-carboxylic acids» (e.g. active pyruvate, etc.). The reaction of 2-(α-hydroxyalkyl)-4-methyl-5-(β-hydroxyethyl)-thiazoles and 2-(α-ethoxycarbonyl-α-acetoxy-alkyl)-4-methyl-5-(β-acetoxyethyl)-thiazoles, respectively, with alkyl, alkenyl and aralkyl haloids, or with 2-methyl-4-amino-5-bromomethyl-pyrimidine hydrobromide results in the quaternary thiazolium compounds belonging to the group of the active aldehydes, active α-oxo-carboxylic acids, etc. According to this method 2-hydroxymethyl-thiamine bromide hydro-bromide has been synthesized, which can be considered as the pyrophosphate-free «active formal-dehyde». The 2-α-hydrogen atom in 2-(α-hydroxyalkyl)-thiazolium compounds cannot be replaced by deuterium under conditions similar to those used for the H → D exchange in thiamine. The main peaks in the mass spectra of 2-(α-hydroxyalkyl) substituted thiazoles and thiazolium quaternary salts are listed.     

The thiazolium-catalyzed Sila-Stetter reaction: conjugate addition of acylsilanes to unsaturated esters and ketones

A new acyl anion addition reaction between acylsilanes and alpha,beta-unsaturated conjugate acceptors promoted by a nucleophilic organic catalyst has been disclosed. The 1,4-dicarbonyl products produced in this reaction are highly useful synthons. Neutral carbenes (or zwitterions) generated in situ from commercial thiazolium salts are used as effective catalysts for the reaction which is in contrast to established anionic catalysts typically employed to promote the required Brook rearrangement (1,2-silyl shift from carbon to oxygen) involved in the reported reaction. This process successfully utilizes acylsilanes as tunable acyl anion progenitors and is tolerant of a wide range of structural diversity on the acylsilane or the conjugate acceptor.     

Polymer-Attached Thiazolium Salts-Catalyzed Addition of Aldehydes to α, β-Unsaturated Carbonyl Compounds

A homogeneous catalyst, 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride, for addition of aldehydes to activated double bond, was attached to 20% cross-linked polystyrene-divinylbenzene copolymer. The attached catalysts could be easily removed from the reaction mixture. Polymer-attached thiazolium salts in the presence of triethylamine are active catalysts for addition of aromatic and aliphatic aldehydes to α,β-unsaturated ketones to yield γ-diketones.     

Multicomponent reactions involving zwitterionic intermediates for the construction of heterocyclic systems: one pot synthesis of aminofurans and iminolactones

The reaction of 1:1 zwitterionic intermediate generated in situ from dimethyl acetylenedicarboxylate (DMAD) and cyclohexyl isocyanide with aldehydes and quinones is described. The reaction of stoichiometric amounts of DMAD, isocyanide and aldehydes afforded 2-aminofurans in good yields, while the reaction with quinones gave iminolactones.     

Novel Synthesis of Oxygenated Coumarins from Substituted Phenols Mediated by Vinyl Triphenylphosphonium Salt Under Microwave Irradiation

Protonation of the highly reactive 1:1 intermediates produced in the reaction between triphenylphosphine and dimethyl acetylenedicarboxylate(DMAD) by substituted phenols lead to vinyl triphenylphosphonium salts, which undergo aromatic electrophilic substitution reaction with a phenolate conjugate base to produce 4-carboxymethyl coumarins in fairly highly yields.     

Thiazolocyanines

A method was developed for the preparation of 2-methyl-N-(2-thiazolyl)-, 2-methyl-N-(2-pyridyl)-, and 2-methyl-N-(2-benzothiazolyl)thiazolium salts. Cyanine dyes were synthesized from these salts. A comparison of the absorption spectra of dyes with various substituents (ethyl, phenyl, and 2-hetaryl) attached to the nitrogen atoms of the thiazole rings of the dyes demonstrated that the color deepens as the electronegativity of these substituents increases.See [1] for communication XIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 933–936, July, 1972.     

Recyclization reactions of heterocycles XVIII. Synthesis and recyclization of thiazolium and benzothiazolium salts

A number of thiazolium salts were obtained, and their reaction with hydrazine was studied. On reaction with hydrazine the aryl-substituted thiazolium salts are recyclized to dihydro-l, 2, 4-triazines, whereas on reaction with monoalkylhydrazines they are converted to 4H, 5H-1, 2-4-triazinium salts; thiazolium salts are converted to hydrazidohydrazones on reaction with phenylhydrazine. Recyclization to the dihydro-sym-tetrazine system was observed for 2-phenyl-substituted benzothiazolium tosylate.See [1] for communication XVII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 635–640, May, 1976.     

On the organocatalytic activity of N-heterocyclic carbenes: role of sulfur in thiamine

The reaction energy profiles of the benzoin condensation from three aldehydes catalyzed by imidazol-2-ylidene, triazol-3-ylidene, and thiazol-2-ylidene have been investigated computationally. The barriers for all steps of all investigated reactions have been found to be low enough to indicate the viability of the mechanism proposed by Breslow in the 1950s. The most remarkable difference in the catalytic cycles has been the increased stability of the Breslow intermediate in case of thiazol-2-ylidene (by ca. 10 kcal/mol) compared to the other two carbenes, which results in lower energy for the coupling of the second aldehyde molecule, thus, increasing the reversibility of the reaction. Since the analogous transketolase reaction, being involved in the carbohydrate metabolism of many organisms, requires an initial decoupling-a reverse benzoin condensation-this difference provides a reasonable explanation for the presence of a thiazolium ring in thiamine instead of the otherwise generally more available imidazole derivatives. The "resting intermediate" found by Berkessel and co-workers for a triazole-based catalyst was found more stable than the Breslow intermediate for all of the systems investigated. The (gas phase) proton affinities of several carbenes were compared, the relative trends being in agreement with the available (in aqueous solution) data. The hydrolytic ring-opening reaction of the thiazole-based carbene was shown to be different from that of imidazole-2-ylidenes.     

用碲ylide合成杂环查尔酮,二烯酮和杂环烯类衍生物

最近,我们用碳酸钾作碱从碲盐在含微量甲酰胺的乙腈中,手室温条件下十分简便地合成了2-或2,4-不饱和腈,酮,酯和酰胺。杂环查尔酮和5-硝基呋喃烯类化合物都是具有生理活性的化合物。为扩大碲ylide的应用并研究杂环基团引入对碲ylide反应活性的影     

Recent application of acidic 1,3-azolium salts as promoters in the solution-phase synthesis of nucleosides and nucleotides

Acidic 1,3-azolium salts are prepared from Brønsted acids and 1,3-azoles such as imidazole, thiazole, and oxazole. Acidic imidazolium salts are frequently employed as promoters for the synthesis of nucleotides using the phosphoramidite method in a solution phase. Recently, it was revealed that thiazolium and oxazolium salts catalyzed Vorbrüggen-type N-glycosylation reactions to give nucleosides. These reactivities are attributed to the stronger Brønsted acidities of the thiazolium and oxazolium salts relative to those of the imidazolium salts. This digest focuses on recent progress in the applicability of acidic 1,3-azolium salts as promoters in the solution-phase synthesis of nucleosides and nucleotides.     

Synthesis of 2-keto-imidazoles utilizing N-arylamino-substituted N-heterocyclic carbenes

A new method for the synthesis of 2-aroyl-, 2-heteroaroyl-, and 2-cinnamoyl-substituted imidazoles in very good yields has been developed. The reaction employs novel nitrogen heterocyclic carbenes (NHCs), namely, N-arylamino-substituted NHCs, formed in situ from the corresponding imidazolium salts, and subsequent reaction with aromatic, heteroaromatic, and cinnamic aldehydes without utilizing transition metals or expensive specialized catalysts.     

Catalytic multicomponent synthesis of highly substituted pyrroles utilizing a one-pot sila-Stetter/Paal-Knorr strategy

[reaction: see text] A multicomponent synthesis of highly substituted pyrroles catalyzed by thiazolium salts has been disclosed. The reaction employs an acyl anion conjugate addition reaction of acylsilanes (sila-Stetter) and unsaturated ketones to generate 1,4-dicarbonyl compounds in situ. The subsequent addition of various amines promotes a Paal-Knorr reaction, affording the desired pyrrole nucleus in an efficient one-pot process.