Preparation of 4-hydroxy-2-alkenenitriles from phrnylsulfinylacetonitrile with keetones or aldehydes,and its synthetic application to substituted furans

The reaction of phenylsulfinylacetonitrile 1 with ketones or aldehydes gave 4-hydroxy-2-alkenenitriles which were converted to 2- and/or 3-substituted furans by the treatment with diisobutylaluminumhydride(DIBAL) followed by acid hydrolysis.     

The palladium catalyzed thienylation of allylic alcohols with 2- and 3-bromothiophenes and their derivatives

Pd catalyzed reaction of allylic alcohols with 2-bromothiophene provides 3-(2'-thienyl)aldehydes or ketones selectively together with the small amounts of 2-(2'-thienyl)aldehydes and ketones. Similarly 3-(3'-thienyl)-aldehydes or ketones were obtained selectively from allylic alcohols and 3-bromothiophene. The reactivity and regioselectivity largely depend on the solvents, additives, and the structure of allylic alcohols. Generally aprotic dipolar solvent such as HMPA and DMF gave the most satisfactory results. 2-Thienyl iodide showed somewhat higher reactivity than 2-thienyl bromide. 2-Thienyl chloride was unreactive. Sodium iodide and/or triphenyl-phosphine were very effective as the cocatalysts especially for the reactions to give aldehydes. This thienylation reaction was also applicable to 2-bromothiophenes with a wide variety of substituents at 5-position. The synthetic utility of this catalytic reaction has been illustrated by the synthesis of 9-oxo-trans-2-decenoic acid (Queen substance).     

Acid catalyzed ring closure reactions of electrophilic alkenes

Treatment of -acyl-,β-unsaturated ketones with sulfuric acid or dimethylformamide-hydrogen chloride or p-toluenesulfonic acid gave rise to 3-acyl-2-alkyl-4,5-dihydrofurans. Similar cyclization of -acyl-,β-unsaturated esters initially afforded 3-alkoxycarbonyl-2-alkyl-4,5-dihydrofurans which were transformed into 2-acylbutanolides on further reaction with sulfuric acid.

This acid catalyzed cyclization is strongly dependent upon the substitution pattern of the electrophilic alkenes, the acid used and reaction conditions.     

Synthesis of picolinohydrazides and their evaluation as ligands in the zinc-catalyzed hydrosilylation of ketones

A set of picolinohydrazides was prepared by reaction between hydrazines and either 2-picolinic acid or ethyl pyridine-2-carboxylate, and characterized. These molecules were evaluated as ligands in the zinc-catalyzed hydrosilylation of ketones. Thus, several aromatic and aliphatic ketones were successfully reduced by diethoxymethylsilane as the hydride source in the presence of a catalytic system made of diethylzinc combined in situ to the picolinohydrazides described herein.     

Synthesis of pyrrolo[3,2-b]indole derivatives

The reaction of N-acetylindoxyl hydrazone with ketones in alcohol gave N-acetylindoxyl alkylindenehydrazones, which were converted to pyrrolo[3,2-b]indole derivatives by treatment with glacial acetic acid. Pyrrolo[3,2-b]indole derivatives were also obtained in the reaction of N-acetylindoxyl hydrazone with ketones in glacial acetic acid. The structures of the synthesized products were confirmed by data from the IR, UV, PMR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 201–205, February, 1982.     

基于乙酸为溶剂和催化剂的芳乙酮Mannich反应

采用乙酸作溶剂和催化剂, 将芳乙酮与甲醛和二级胺进行Mannich反应及热解反应, 并未得到预期的Mannich碱或α,β-不饱和酮(2), 而是以较高产率(65%~73%)生成了乙酸(2-芳甲酰基)烯丙酯(3a~3o). 通过核磁共振波谱、 高分辨质谱和红外光谱表征了化合物3a~3o的结构, 研究了此“异常”反应的发生条件, 并提出了可能的反应机理. 结果表明, 芳乙酮的特殊结构及反应中过量的乙酸是产生化合物3a~3o的决定因素.     

Induced halogenation of alkyl cyclohexenyl ketones involving metal halides,hydrohalogenic acids,and hydrogen peroxide

The induced halogenation and hydroxyhalogenation of alkyl cyclohexenyl ketones in a system [MHlg + HHlg or HHlg]-H₂O₂ or in NaOCl was performed and optimum reaction conditions were established. Under mild conditions the electrophilic addition of the halogen or the acid occurred at the multiple bond of the ring with the formation of the corresponding dihalo or hydroxyhalo derivatives of cycloaliphatic ketones. From the compounds obtained epoxy- and dioxyketones of aliphatic series were prepared. Chloro(bromo)hydrins of ketones from the alkylcyclohexane series and oxiranes based thereon are reactive compounds and can be employed as synthons in the organic synthesis.     

3-Pyrrolidinecarboxylic acid for direct catalytic asymmetric anti-Mannich-type reactions of unmodified ketones

We report the development of direct catalytic, enantioselective, anti-selective Mannich-type reactions between unmodified ketones and alpha-imino esters under mild conditions. The reactions were performed using 5-10 mol % of (R)-3-pyrrolidinecarboxylic or (R)-beta-proline as catalyst in an environmentally benign solvent, 2-PrOH, at room temperature. The anti-Mannich products were obtained in good yields with high diastereo- and enantioselectivities (up to anti/syn >99:1, 99% ee). While (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid is an excellent catalyst for the anti-Mannich-type reactions of aldehydes, it did not efficiently catalyze the corresponding Mannich-type reactions of ketones; (R)-3-pyrrolidinecarboxylic acid did efficiently catalyze the Mannich-type reactions of ketones. (S)-Proline or (S)-2-pyrrolidinecarboxylic acid has been reported to catalyze the Mannich-type reactions of ketones to afford the syn-products. Thus, the position of the carboxylic acid group on the pyrrolidine ring directs the stereoselection of the catalyzed reaction, providing either syn- or anti-Mannich products.     

烯基取代的甲酸态四氢叶酸辅酶模型的合成及其碳单元转移反应

以邻苯二胺和乙酸为原料,经3步反应合成了8种烃基乙烯基取代的苯并咪唑盐,其结构用元素分析,¹HNMR,IR,MS和UV-Vis进行了表征,并以其作为取代的甲酸态四氢叶酸辅酶模型,同亲核试剂(格氏试剂)反应得到烃基乙烯基取代的一碳单元完全转移的产物α,β-不饱和酮,为α,β-不饱和酮的合成提供了一种简便的仿生合成新方法.     

Rapid and Efficient Microwave-Assisted Friedländer Quinoline Synthesis

A microwave-based methodology facilitates reaction of 2-aminophenylketones with cyclic ketones to form a quinoline scaffold. Syntheses of amido- and amino-linked 17β-hydroxysteroid dehydrogenase type 3 inhibitors with a benzophenone-linked motif were pursued using 2-aminobenzophenone as building block. Two amido-linked targets were achieved in modest yield, but when using microwave-assisted reductive amination for the amino-linked counterparts an unexpected product was observed. X-ray crystallography revealed it as a quinoline derivative, leading to optimisation of a simple and efficient modification of Friedländer methodology. Using reagents and acetic acid catalyst in organic solvent the unassisted reaction proceeds only over several days and in very poor yield. However, by employing neat acetic acid as both solvent and acid catalyst with microwave irradiation at 160 °C quinoline synthesis is achieved in 5 minutes in excellent yield. This has advantages over the previously reported high temperatures or strong acids required, not least given the green credentials of acetic acid, and examples using diverse ketones illustrate applicability. Additionally, the unassisted reaction proceeds effectively at room temperature, albeit much more slowly.     

Reactions of 1,3-isothiocyanato ketones with mineral acids. Synthesis of 3,4-dihydro-2H,1,3-thiazin-2-ones

Reactions of 1, 3-isothiocyanato ketones with mineral acids formed 3, 4-dihydro-2H, 1, 3-thiazin-2-ones or their mixtures with 6-alkylidenetetrahydro-1, 3-thiazin-2-ones. Subsequent acid hydrolysis of the thiazines obtained formed salts of 1,3-amino ketones. The direction and extent of the transformation depend on the nature of the acid, reaction temperature, and structure of the 1,3-isothiocyanato ketones.Omsk State University, Omsk 644077. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 850–854, June, 1996. Original article submitted October 18, 1995.Deceased.     

Synthesis of new thieno[2,3‐d]pyrimidines,thieno[3,2‐e]pyridines,and thieno[2,3‐d][1,3]oxazines

o‐Aminothiophene dicarbonitrile 1 on neat reaction with cyclic ketones in anhydrous ZnCl₂ yielded mixture of fused aminopyridine 3 and iminospirooxazine 4 derivatives. Similarly, pyrimidine derivatives 5 and 8 were obtained by the reaction of this intermediate 1 with formic acid and DMF‐DMA followed by hydrazine hydrate, respectively. The reaction of o‐amino‐thiophene dicarboxamide 2 at ambient temperature with cyclic ketones yielded spiropyrimidine 10 as a sole product in quantitative yield. The regioselective anellated pyrimidine 9 , 11 , and dihydropyrimidine 12 derivatives were also obtained by the reaction with aromatic aldehydes in presence of piperidine and iodine respectively. J. Heterocyclic Chem., (2012).     

Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and alkyl halides

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.     

Efficient PhB(OH)2-catalyzed one-pot synthesis of 3-substituted isoindolin-1-ones and isobenzofuran-1(3H)-ones under solvent free conditions

An efficient and practical one-pot synthesis of 3-substituted isoindolin-1-ones and isobenzofuran-1(3H)-ones has been developed under solvent free-conditions using non-toxic and cheap phenylboronic acid as excellent catalyst. This strategy involves the sequential two-step Mannich/lactamization cascade reaction of inexpensive 2-formylbenzoic acid with primary amines and a wide variety of ketones, and an aldol/lactonization cascade reaction of 2-formylbenzoic acid with a broad range of ketones.     

Isocyanide based multicomponent reactions of oxazolidines and related systems

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an ¹⁸O labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products.     

A general synthetic route to chiral dihydroxy-9,9′-spirobifluorenes

C₂-Symmetric 9,9′-spirobifluorenes with 2,2′-, 3,3′-, and 4,4′-dihydroxyls were conveniently prepared from 1,2-dibromobenzene. The palladium-catalyzed coupling reaction of 1,2-dibromobenzene with methoxyphenylmagnesium bromide or methoxyphenylboronic acid provided methoxy substituted 2-bromobiphenyls. Lithium-bromine exchange with n-butyllithium, followed by reaction with dimethyl carbonate afforded di[2-(methoxyphenyl)phenyl]ketones as the key intermediates. A continuous ring-closure induced by a strong Lewis acid and demethylation gave dihydroxy-9,9′-spirobifluorenes. The racemic dihydroxy products were resolved by inclusion crystallization using chiral resolving reagents or separated by chiral HPLC.     

Synthesis of Mannich type products via a three-component coupling reaction

The reactions of alkyl nitriles, acetyl chloride, aldehydes and β-ketoesters or simple ketones was studied for the one-pot synthesis of β-acetamido carbonyl compounds. It was observed that the reaction proceeds in the absence of Lewis acids. However, a Lewis acid catalyzes the reaction and several were tested. It was found that whereas Cu(OTf)₂ is suitable for the coupling of β-ketoesters with aldehydes, Sc(OTf)₃ is the best for ketones. A possible mechanism is proposed based on the isolation and characterization of an intermediate.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Regioselective synthesis of 1-alkyl- or 1-aryl-1H-indazoles via copper-catalyzed cyclizations of 2-haloarylcarbonylic compounds

[reaction: see text] A general method for the one-step regioselective synthesis of 1-alkyl- or 1-aryl-1H-indazoles from ortho-halogenated alkanoylphenones, benzophenones, and arylcarboxylic acids, via copper-catalyzed amination, was developed by using 0.2% mol of CuO in the presence of K(2)CO(3). The reaction involves amination followed by intramolecular dehydration. Different functionalized alkyl aryl ketones, diaryl ketones, and benzoic acid derivatives were efficiently coupled with several hydrazines. Ligands commonly employed as catalysts for intermolecular amination were shown to be ineffective for this cyclization.     

Reaction of α,β‐unsaturated ketones using cerium (IV) sulfate tetrahydrate in acetic acid

The reaction of α,β‐unsaturated ketones with cerium (IV) sulfate tetrahydrate [Ce(SO₄)₂·4H₂O, CS] in acetic acid gave the corresponding β‐acetoxy ketones. In the case of 2‐cyclohexen‐1‐one with CS in acetic acid, benzobicyclo[2.2.2]octen‐2‐one was obtained. The reaction mechanism also was proposed. Moreover, we report the aromatization and esterification of (R)‐(?)‐carvone by CS in acetic acid. Copyright © 2007 John Wiley & Sons, Ltd.