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.     

Synthesis of chiral isoquinuclidines and determination of their absolute configuration

A route to 1,2-dihydropyridines N¹-substituted with chiral auxiliaries has been developed starting from commercially available chiral amines. Cycloaddition between these dihydropyridines and methyl acrylate gave, in moderate d.e., isoquinuclidines of good enantiomeric purity whose absolute configuration has been established.     

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.     

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.     

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.     

Direct access to marine pyrrole-2-aminoimidazoles, oroidin, and derivatives, via new acyl-1,2-dihydropyridin intermediates

[reaction: see text] A short synthesis of the C(11)N(5) oroidin derivatives is reported. The key step of the strategy is a one-pot oxidative bromine-mediated addition of protected guanidines to the N-acyl-1,2-dihydropyridines 9a-c. The new N-acyl-1,2-dihydropyridines were prepared directly from pyridine and pyrrole-2-carbonyl chloride by reduction with borohydride reagent in one step.     

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.     

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%).     

Electrochemical transformations of 4-(nitroaryl)-1,2- and -1,4-dihydropyridines in acetonitrile

The potentials of the electrolytic oxidation and reduction of 3,5-diethoxycarbonyl- 1,2- and -1,4-dihydropyridines with a nitroaryl substituent in the 4 position and their oxidized forms were determined by the method of a rotating disk electrode with a ring. The mechanism of the electrochemical oxidation of the starting dihydropyridines in acetonitrile on a graphite electrode was ascertained. The first step in the electrolytic reduction of the starting dihydropyridines is the addition of an electron to the nitro group to give anion radicals, the fine electronic structures and the hyperfine structure (hfs) constants of which were determined by EPR spectroscopy. The pyridinium fragment in the electrolytic oxidation products is reduced more readily than the nitro group in the aryl substituent.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1099–1105, August, 1985.     

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.     

Synthesis and synthetic utility of 1-acyl-2-alkyl-4-trimethylstannyl-1,2-dihydropyridines

1-Acyl-2-alkyl-1,2-dihydropyridines were prepared from 4-trimethylstannylpyridine and Grignard reagents. This methodology was utilized in the synthesis of N-methyl-2-azatricyclo[5.3.1.0]undecane.     

(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.     

New derivatives of 4-aryl-2,6-dimethyl-3,5-diacetyl-1,4- and 1,2-dihydropyridines

4-Aryl-1,2,6-trimethyl-3,5-diacetyl-1,4-dihydropyridines and the corresponding pyridinium salts, which upon reduction with NaBH₄ form 4-aryl-1,2,6-trimethyl-3,5-diacetyl-1,2-dihydropyridines, were synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 508–513, April, 1983.     

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.     

Diels-alder cycloadditions of N-substituted-1,2-dihydropyridines with 1,2,4-triazoline-3,5-diones and maleimides

The reaction of N-substituted-1,2-dihydropyridines 1 with 1,2,4-triazoline-3.5-diones 2 and maleimides 9 proceeds stereospecifically to afford endo cycloaddition products. N-Acetyl-1,2-dihydropyridines react with 2 to afford a stereo isomeric mixture of 3 and 4 whereas those possessing a N-ethoxycarbonyl, methoxycarbonyl, methanesulfonyl or benzenesulfonyl substituent yield 3 exclusively: similar results are also obtained in reactions employing maleimides. Stereochemistry was assigned on the basis of nmr data and use was made of the anisotropic effects of the 7,8 unsaturation on the R₁ and R₂ substituents.     

Regio- and chemoselective addition of alkynyltin reagents to the 2-position of 3-acylpyridines activated by methyl chloroformate: selective synthesis of 2,3-disubstituted 1,2-dihydropyridines

Alkynyltin reagents add to the 2-position of 3-acylpyridines activated by methyl chloroformate regio- and chemoselectively to give 2,3-disubstituted 1,2-dihydropyridines, whereas alkynyl Grignard reagents suffer from a lack of regio- or chemoselectivity.     

A carbon-carbon bond formation using endoperoxides of 1,2-dihydropyridines

A novel type of a nucleophilic substitution on the piperidine ring was achieved by a stannous chloride-effected reaction of endoperoxides of N-alkoxycarbonyl-1,2-dihydropyridines with various kinds of carbon nucleophiles.     

Synthesis and structure of new substituted 2-dicyanomethylene-1,2-dihydropyridines

The synthesis of substituted 2-dicyanomethylene-1,2-dihydropyridines 3b-c and 2-dicyanomethylene-2,3,4,5-tetrahydropyridine 4 is accomplished from malononitrile dimer and propenenitriles 2 . All structures were determined by nmr techniques; however to put our structural assignment for 6-amino-3-cyano-5-ethoxycarbonyl-2-dicyanomethylene-1,2-dihydropyridine 3d on a firm and unequivocal basis we decided to perform X-ray diffraction analysis of this compound.     

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’.