Vicinal diamination of 1,4-dihydropyridines (original) (raw)
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Tetrahedron, 2001
AbstractÐChiral 1,4-dihydropyridines were prepared by the regio-and stereoselective addition of ketene silyl acetals and organometallic reagents to pyridinium salts. In the addition reaction, an intramolecular interaction between the thiocarbonyl or carbonyl with the pyridinium nucleus plays an important role in bringing about the selectivities. The absolute con®guration of the newly produced stereogenic center of the 1,4-dihydropyridines was determined by X-ray analysis and CD Cotton effects after conversion into the appropriate derivatives. The working model for the stereoselectivity was proposed based on the ab initio calculations at the RHF/3-21G p level. q
Scope and Limitations of an Efficient Four-Component Reaction for Dihydropyridin-2-ones
The Journal of Organic Chemistry, 2010
A broad range of isonitrile-functionalized 3,4-dihydropyridin-2-ones could be prepared using a fourcomponent reaction between phosphonates, nitriles, aldehydes, and isocyanoacetates. The reaction involves initial formation of a 1-azadiene intermediate which is trapped in situ by an isocyanoacetate to give the desired heterocyclic scaffold through cyclocondensation. The full scope and limitations of this four-component reaction are described. Variation of the nitrile and aldehyde inputs proved to be extensively possible, but variation of the phosphonate input remains limited. Regarding the isocyanoacetate, R-aryl isocyanoacetates give moderate to high yields and result in a complete diastereoselectivity for the 3,4-cis isomer. R-Alkyl isocyanoacetates gave the corresponding dihydropyridin-2-ones in moderate yields, most of them as mixtures of diastereomers. Elevated temperatures during cyclocondensation generally increased the yield and resulted in a change of the diastereomeric ratio in favor of the cis-diastereomer. In addition to isocyanoacetates, a limited number of other R-acidic esters resulted in the formation of dihydropyridin-2-ones, albeit in much lower yield. Computational studies show that the observed difference in yield cannot be simply correlated to specific physical properties (including acidity) of the different R-acidic esters.
Tetrahedron Letters, 1999
Diastereoface-selective asymmetric addition of organometallic reagents to pyridinium salts of 1 and 2 was performed to give chiral 1,4-dihydropyridines in good regio-and stereoselectivities. The absolute configuration of the newly-produced chiral center was determined by X-ray analysis after derivation to menthyloxycarbamate 10. Neighboring group participation of the thiocarbonyl group to the pyridinium nucleus was predicted by PM3 calculations of the intermediary pyridinium salts, which may play an important role in the generation of stereoselectivity.
A convenient synthesis of 1,2-dihydropyridine (1,2-DHP) has been developed from dienaminodioate and an imine mediated by trifluoroacetic acid in a one-pot cascade synthesis. The advantages associated with this transformation include conditions that are metal-free, room temperature, undistilled solvent, and expeditious in excellent yields. The substrate scope has been demonstrated with various aromatic, heteroaromatic, unsaturated aldehydes, and anilines, benzylic amines in impressive yields.
A new synthetic approach to N-substituted 1,4-dihydropyridines
Tetrahedron, 2001
AbstractÐSome novel N-substituted 1,4-dihydropyridines (DHPs) (15a±d) have been synthesized by reaction of 2-amino-5-formyl-4Hpyran (10) with primary amines. Formation of 1,4-DHPs involves ring cleavage of the 4H-pyran ring by nucleophilic attack of the respective amine and subsequent 6-exo-dig cyclization. Treatment of the pyran system 10 with hydrazines under the same reaction conditions leads, however, to the corresponding hydrazone derivatives 12a,b. Two different reaction routes are observed depending whether the amine or hydrazine derivative is used as nucleophilic reagent. A competition between 1,4 versus 1,2 addition reaction pathway is proposed. q
Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates
Molecules, 2015
The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines as without it the reaction does not proceed at all. The aminolysis reaction proceeded regioselectively, as the alkyl ester conjugated with the 1,4-dihydropyridine cycle was not involved in the reaction. Screening of other N-containing bases, such as triethylamine (TEA), pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), imidazole, tetramethyl guanidine (TMG) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as catalysts revealed no activity in the studied reaction.
Tetrahedron, 2008
The reactions of 5-pyrrolyl-pyrimidinyloxyacetaldehyde or methyl ketone with primary amines yielded hydroxymethylpyrrolopteridine derivatives via a cascade of iminium cyclization and O-N Smiles rearrangement. The present cascade exhibited a different profile compared to the previously reported ones, which consisted of N-N Smiles rearrangement. Lewis acid (TiCl 4 ) under carefully controlled conditions was employed to suppress the competing formation of imine dimers to give the desired heterocycles. A plausible mechanism involving the iminium cyclization and Smiles rearrangement is proposed. This methodology has been used to generate a series of 6-hydroxymethylpyrrolo[1,2-f]pteridine derivatives with potential biological activities.