1.4- Dihydropyridine-3-carboxaldehydes

Chiral aminals 1,4-dihydropyridine-3-carboxaldehydes.1 The chiral aminal 2 prepared from pyridine-3-carboxylaldehyde and (S,S)-12 reacts with organocopper reagents in the presence of methyl chloroformate to give almost exclusively products of 1,4-addition, as expected from reactions of the free aldehyde.3 No products of 1,2-addition are formed, but 1,6-adducts are minor products in some cases. The 1,4-adducts are formed in 82-93% de (R-configuration). Addition of butyl and ethyl groups is best effected with lithium cuprates, but addition of methyl, vinyl, or aryl groups is best effected with organomagnesium cuprates. Under these conditions,... 

An investigation of alkylation of 1,1-enediamines with a,/ -unsaturated aldehydes and ketones has been recently conducted by Jones and Hirst36. The reaction of 1,1-enediamine 93 and a,/ -enals affords the fused 1,4-dihydropyridines 133, via a nucleophilic addition and intramolecular dehydration sequence (equation 49). 93 reacts with propenal, however, to give the cyclohexene carboxaldehyde 134 in almost quantitative yield (equation 50). The formation of 134 is most probably due to addition of 93 to two... 

A synthesis of 4-alkyl-3-pyridinols (55) from 3-benzyloxypyridine (52) utilizes a copper-catalyzed Grignard reaction. The dihydropyridine intermediates 53 are aromatized to 4-alkyl-3-benzyloxypyridines (54), which on hydrogenolysis provide the pyridinols 55 (85JHC1419). Substitution at the 4-position of 3-pyridinecarboxaldehydes can be achieved via 1-acylpyri-dinium salt 56. The intermediate acetal 57 is hydrolyzed to give pyridine-carboxaldehyde 58 (84H339). 

Shinkai and Bruice (21, 22) recently have described the first example of a zinc-ion-catalyzed reduction of aldehyde by NADH and NADH analogs in aqueous solution. They found that 3-hydroxypyridine-4-carboxaldehyde derivatives are reduced by 1,4-dihydropyridines in aqueous methanol (52% by weight) at 30°. Furthermore, this reaction is subject to catalysis by divalent metal ions, including Zn(II), Eq. (9). The following apparent relative order for metal ion effectivenes was observed Ni2+>Co2+>Zn2+>Mn2+>Mg2+>control. 

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