One-pot synthesis of 1,2-dihydropyridines: expanding the diverse reactivity of propargyl vinyl ethers

The catalyzed synthesis of 1,2-dihydropyridines starting from easily accessible propargyl vinyl ethers was realized. The reaction sequence involving a transition metal-catalyzed propargyl-Claisen rearrangement, a condensation step, and a Br?nsted acid-catalyzed heterocyclization furnishes the highly substituted heterocycles in moderate to excellent yields. Additionally, a practical one-pot protocol toward 1,2-dihydropyridines and 2H-pyrans starting from propargylic alcohols was developed.     

Pt(II)-catalyzed synthesis of 1,2-dihydropyridines from aziridinyl propargylic esters

Pt(II)-catalyzed cycloisomerization of aziridinyl propargylic esters affords 1,2-dihydropyridines with regiodefined installation of substituents. A mild conversion of the 1,2-dihydropyridines to the corresponding substituted pyridines as well as chirality retention from the aziridinyl propargylic ester substrates have been demonstrated.     

Synthesis using pyridinium anhydrobases,preparation of indolizine derivatives

A number of derivatives of indolizine ring system have been prepared from 1-substituted 4,6-diphenyl-2-phenacylidene-1,2-dihydropyridines either by metallation with LDA or acylation and further basic treatment. Similarly, I-arylmethyl-4,6-diphenyl-2-dicyanomethylene-1,2-dihydropyridines by action of LDA undergo cyclization to the corresponding 2-amino-1-cyano-3-aryl indolizines.     

Organocatalyzed regioselective and enantioselective synthesis of 1,4- and 1,2-dihydropyridines

Abstract

Herein, we introduce one of the first examples of asymmetric organocatalyzed synthesis of 1,2-dihydropyridines, affording enantioselective access to and partially solving regioselectivity challenges in the synthesis of dihydropyridines. We demonstrate that through modification of organocatalysts both 1,2- and 1,4-dihydropyridines (1,2- and 1,4-DHPs) can be obtained with high regioselectivity (ratio of 1,2-DHP/1,4-DHP from 95/5 to 0/100) and enantioselectivity (33% ee for 1,2-DHPs and up to 98% ee for 1,4-DHPs) in good yields (up to 87%).     

Nucleophilic addition to 3-substituted pyridinium salts: expedient syntheses of (-)-L-733,061 and (-)-CP-99,994

[reaction: see text] The addition of nucleophiles to 3-substituted pyridinium salts prepared from N-methylbenzamide and various pyridines has been investigated. Good to excellent regioselectivities favoring the 2,3-disubstituted 1,2-dihydropyridines were observed. The resulting 1,2-dihydropyridines led to the corresponding 2,3-disubstituted pyridines upon treatment with Mn(OAc)3/NaIO4. This methodology was also successfully applied to the enantioselective syntheses of (-)-L-733,061 and (-)-CP-99,994, two members of a new class of highly potent, nonpeptide, Substance P antagonists.     

Palladium-catalyzed regioselective silaboration of pyridines leading to the synthesis of silylated dihydropyridines

The addition of silylboronic esters to pyridine takes place in toluene at 50 °C in the presence of a palladium catalyst to give N-boryl-4-silyl-1,4-dihydropyridines in high yield. The regioselective 1,4-silaboration also proceeds in the reaction of 2-picoline and 3-substituted pyridines, whereas 4-substituted pyridines undergo 1,2-silaboration to give N-boryl-2-silyl-1,2-dihydropyridines regioselectively.     

Syntheses of Racemic Diaminosugar Derivatives Starting from 1,2-Dihydropyridines and from Nitrosobenzene

Racemic diaminosugars were easily obtained by a regio- and stereoselective three-step synthetis. In the first step, regiospecific hetero-Diels-Alder cycloadditions between 1,2-dihydropyridines 1a and 10 and nitrosobenzene led to the bicyclic compounds 2a and 11 , respectively, cis-Glycol formation starting from these latter adducts, followed by hydrogenolysis of the N? O bond and by exhaustive acetylation of the OH-groups, led to the diaminolyxose 5 , the diaminomannose 14 and the diaminoallose 15 . When starting from benzyl 1,2-dihydropyridine-1-carboxylate ( 1b ) and using the same reaction sequence, the racemic piperidine derivative 8 was obtained.     

The addition of alkylzinc iodides to 1-(phenoxycarbonyl)pyridinium salts

Several 1-(phenoxycarbonyl)-1,2-dihydropyridines were prepared by the addition of alkylzinc iodides to 1-(phenoxycarbonyl)pyridinium salts.     

2-Aryl-3,5-dinitro-1,2-dihydropyridines

The reaction of -nitroacetaldehyde with paraformaldehyde or aromatic aldehydes and ammonium acetate in acetic acid yielded 2-aryl-3,5-dinitro-1,2-dihydropyridines. Aromatic aldehydes, in an ethanol and acetic acid mixture, gave isomeric 3,5-dinitro-1,4-dihydropyridines in addition to 1,2-dihydropyridines. Physicochemical properties and reactivities of the compounds have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 64–70, January, 1993.     

(Dihydropyridine)iron tricarbonyl complexes

(N-Carboalkoxy-1,2-dihydropyridine)iron tricarbonyl complexes have been isolated by treatment of either N-carboalkoxy-1,2 or -1,4-dihydropyridines with diiron ennecarbonyl. The organic ligand was liberated from these complexes by use of trimethylamine oxide.     

A new method for regioselective synthesis of 2-substituted 1-(methoxycarbonyl)-1,2-dihydropyridines

2-Substituted 1,2-dihydropyridines including an optically active one were regioselectively prepared from 2-substituted piperidines through three intermediates, that is, (a) 1,2,3,4-tetrahydropyridines, (b) 5-bromo-6-methoxypiperidines, and (c) 1,2,3,6-tetrahydro- 6-methoxypyridines.     

An intramolecular journey of a carboxyl group around 1,2-dihydropyridines: multisite δ- versus γ-lactonization reactions

In contrast to substituted 4-acetic acid 1,4-dihydropyridines, giving only δ-lactones upon intramolecular reactions, 2-substituted 1,2-dihydropyridines led, besides to δ-lactones, also to new, structurally interesting γ-lactones as the result of a bromine-induced carbon-carbon double bond ‘Umpolung’.     

Preparation of pyridinium ylids, 1,4-dihydropyridines,and indolizines from γ-nitrophenyl- and γ-nitrobenzyl-pyridines

The transformations of N-phenacyl(p-nitrophenacyl, benzyl)-2,5-dimethyl-4-nitrophenyl (nitrobenzyl, benzyl)pyridinium bromides under the influence of potassium carbonate solution were studied. Stable pyridinium ylids were obtained in the case of -phenylpyridines that contain a nitro group in the benzene ring and in the case of -benzylpyridines with an N-nitrosubstituted phenacyl group. The conclusion that electron-acceptor substituents have a stabilizing effect on the stability of the ylids was confirmed. Under these conditions -nitrobenzyl derivatives are converted to substituted 1,4-dihydropyridines. The positions at which deprotonation of the starting quaternary pyridinium salts occurs and the formation of 1,4- and 1,2-dihydropyridines were established by PMR spectroscopy. The corresponding pyridinium salts were converted to a new group of indolizines containing a p-nitrophenyl (p-nitrobenzyl) substituent in the 2 or 7 position by the Chichibabin method. It was established that substituted dihydropyridines are converted to indolizines; ideas that confirm the scheme of the previously proposed mechanism for the formation of indolizines through a step involving ylids are expressed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 384–389, March, 1979.     

A novel one-pot, three-component reaction: formation of tricyclic 1,2-dihydropyridines via mesomeric betaines

A one-pot, three-component reaction of pyridine, thiophthalimide and acyl chloride gives novel tricyclic 1,2-dihydropyridines regio- and stereoselectively, in which a mesomeric betaine would be a key intermediate for [4+2]-cycloaddition reaction with thiocarbonyl compounds.     

Selective partial hydrogenation of N-substituted-3-carbamoylpyridinium salts to corresponding dihydropyridines catalyzed by bis(dimethylglyoximato)chloro(pyridine)cobalt

Partial hydrogenation of N-substituted-3-carbamoylpyridinium salts (substituent = benzyl or 2-propyl) proceeded selectively when catalyzed by bis(dimethylglyoximato)chloro(pyridine)cobalt in methanol at room temperature. Chemoselectivity was dependent on the hydrogen pressure, the reaction vessel, and the type of base used. No overreduction to tetrahydropyridines was observed in the presence of NaHCO₃, even under 100 kg cm⁻² of hydrogen. The reaction was also 81–100% regioselective for 1,4-dihydropyridines over 1,6- or 1,2-dihydropyridines.     

Synthesis of 2-substituted 3-nitro-1,2-dihydropyridines by heterocyclic annulation reactions of a sec-nitrodienamine with aldehyde compounds

The reaction of a sec-nitrodienamine 3 with aldehyde compounds afforded 2-substituted 3-nitro-1,2-dihydropyridines 5, providing a heterocyclic annulation reaction.     

Regioselective synthesis of 1,2-dihydropyridines by rhodium-catalyzed hydroboration of pyridines

Pyridine undergoes addition of pinacolborane at 50 °C in the presence of a rhodium catalyst, giving N-boryl-1,2-dihydropyridine in a high yield. The selective 1,2-hydroboration also takes place in the reactions of substituted pyridines. In the reaction of 3-substituted pyridines, 3-substituted N-boryl-1,2-dihydropyridines are formed regioselectively.     

Synthesis and structures of 1-[1-(4-R-benzoyl)-2-ethoxyvinyl]-2-dicyanomethylene-1,2-dihydropyridines

The reaction of (4-R-benzoyl)(2-bromopyridinitim) methylides with ethoxyrnethylene-rnalononitrile is stereoselective and affords Z-1-[1-(4-R-benzoyl)-2-ethoxyvinyl]-2-dicyationietliylene-1,2-dihydropyridines. The structure of 1-[1-(4-chlorobenzoyl)-2 ethoxyvinyll-2-dicyanomethylene-1,2-dihydropyridine has been established by X-ray structural study.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 434–436, February, 1996.     

Steric and electronic substitution effects on the thermal oxidation of 5-carboethoxy-2-oxo-1,2,3,4-tetrahydropyridines

Various 4-aryl substituted 5-carboethoxy-2-oxo-1,2,3,4-tetrahydropyridines were oxidized to their corresponding 4-aryl-5-carboethoxy-2-oxo-1,2-dihydropyridines by potassium peroxydisulfate in aqueous acetonitrile under thermal conditions. The products were obtained in good to excellent yields. Based on the proposed mechanism, the removal of the hydrogen from the C₄-atom of the heterocyclic ring by the hydroxyl radical formed in situ is occurred in the rate determining step, which is influenced by the steric and electronic effects of the substituted aryl group attached to this atom and also the stability of the radical intermediate involved in the oxidation reaction. The experimental results were supported by the computational studies.     

(－)-7(R)-羟罗汉脂素的全合成研究

以4-戊烯酸及(R)-4-苯基-2-噁唑烷酮为起始原料, 以氯化镁在三乙胺和三甲基氯化硅存在下催化的(R)-4-苯基-3-戊烯酰基-2-噁唑烷酮的埃文斯（Evans)反式羟醛缩合反应为关键步骤, 经9步反应合成了(－)-7(R)-羟罗汉脂素, 其光谱数据与文献报道的天然产物一致.