2,3 -Dihydropyridines, instability

The 2,5-, 2,3- and 3,4-dihydropyridines have received very little study regarding their reactivity toward electrophilic reagents. This is undoubtedly due to their instability and the low number of authentic derivatives that are known. 

The other dihydropyridines containing electron-deficient 7r-systems should also be capable of undergoing cycloaddition reactions. However, the instability of these compounds and lack of general methods for their preparation have precluded their study. In principle both the 2,3- and 3,4-dihydropyridines could behave as heterodienes in the Diels-Alder reaction. Although these reactions are known for the 2-azadienes, lack of information in the literature on 1-azadienes suggests that they will be reluctant to participate in cycloadditions double bonds present in the 2,5-dihydropyridine are isolated and would only be expected to behave as two-electron partners in cycloaddition reactions. 

Reduction with isolated enzymes avoids difficulties associated with diffusion limitations and also avoids the presence of many different enzymes, present in the whole cell, which can cause side reactions or reduced enantioselectivity. The main drawback, however, is the instability of the isolated enzyme and the requirement for added co-factor NAD(H) or NADP(H), which are the oxidized (or reduced) forms of nicotinamide adenine diphosphate or its 2 -phosphate derivative. These co-factors are expensive, but can be used as catalysts in the presence of a co-reductant such as formate ion HCOO or an alcohol (e.g. isopropanol or ethanol). The reduction of ketones occurs by transfer of hydride from the C-4 position of the dihydropyridine ring of NADH or NADPH (7.105). Only one of the two hydrogen atoms is transferred and this process occurs within the active site of the enzyme to promote asymmetric reduction. 

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