Mechanism of the Reduction with NAD P H Models

Discussion in the previous section raises the question, how the 1,4-dihydropyridine moiety releases a negative species, hydride , after being coordinated by a metal ion that has an electron-withdrawing property. To answer the question and to consider the molecular arrangement in the transition state of the asymmetric reduction we must deal with the mechanism of the reduction by 1,4-dihydropyridine derivatives. 

Based on the fact that the hyd -dihydropyridine ring transfers d hydride transfer mechanism propos in early days has been accepted consider the polarization where on a less electronegative hydr connection it was suggested that an initial one-electron transfer corresponds to an ion radical between the substrate and the 1, electron transfer mechanism (ET Steffens and Chipman (1971) bas kinetic isotope effect associated 

However, such a discrepancy between two isotope effects was also observed in dry acetonitrile solution, where no side reaction took place (Ohno et al. 1981a). This evidently indicates that a certain step precedes the hydrogen transfer, which can be regarded as an electron transfer step, and that the existence of an intermediate or 

It should be noted that the electron transfer process we are now interested in is the process associated with a certain degree of kinetic isotope effect (Okamoto et al, 1977a). The process is also the subject of base catalysis (Okamoto et al. 1977b). In this sense, the process is completely different from a physical process (Martens et al. 1978), in which the movement of an electron is faster than the movement of an atomic nucleus (Franck-Condon principle). 

It has also been suggested that the reduction by 1,4-dihydropyri-dine derivatives proceeds by a one-step hydride transfer mechanism (HT-mechanism), which seems to be contrary to the ET-mechanism described above. This assertion is mostly based on the results from the reduction of cationic substrates such as quinolinium salts, acridinium salts, and protonated Schiff bases (Srinivasan et al. 1982). For example, Ostovic et al. (1983) reported that the value of the kinetic isotope effect does not change significantly for the reactions with a series of substrates with which equilibrium constants change widely. 

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