Carbonyl compounds with NADH model

The catalytic effect of metal ions such as Mg2+ and Zn2+ on the reduction of carbonyl compounds has extensively been studied in connection with the involvement of metal ions in the oxidation-reduction reactions of nicotinamide coenzymes [144-149]. Acceleration effects of Mg2+ on hydride transfer from NADH model compounds to carbonyl compounds have been shown to be ascribed to the catalysis on the initial electron transfer process, which is the rate-determining step of the overall hydride transfer reactions [16,87,149]. The Mg2+ ion has also been shown to accelerate electron transfer from cis-dialkylcobalt(III) complexes to p-ben-zoquinone derivatives [150,151]. In this context, a remarkable catalytic effect of Mg2+ was also found on photoinduced electron transfer reactions from various electron donors to flavin analogs in 1984 [152], The Mg2+ (or Zn2+) ion forms complexes with a flavin analog la and 5-deazaflavins 2a-c with a 1 1 stoichiometry in dry MeCN at 298 K [153] ... 

Many of the observed attributes of enzymes arise by natural selection in order to help the host organism survive and reproduce. Benner et al. have proposed that one such attribute, the stereospecificities of dehydrogenases, has functional significance based on stereochemical arguments (18, 79). The central features of their functional model can be summarized as follows. The stereospecificities of dehydrogenases acting on alcohols are correlated with the equilibrium constant for the alcohol-carbonyl redox reaction as listed in Table IV (18). Enzymes catalyzing reactions where the eq is <10 " ilf transfer the pro-S proton from NADH when is >10"" Af, the pro-R proton is transferred. Thus the more readily reduced carbonyl compounds use the pro-R proton, but the more difficult to reduce carbonyl compounds use the pro-S proton. The proposed correlation is restricted to simple aldehydes and ketones (i.e., without additional chemistry that would influence the equilibrium constant, such as cyclizations of polyols or formation of lactones). The natural substrate of the enzyme must be well... 

So far, no example of reduction has been reported in the literature using a catalytic system relying on planar chirality. However, ansa-derivatives of Hantzsch esters were developed by Kanomata and Nagata [58] as NADH model compounds (Scheme 8.20). These reagents displayed excellent hydrogen transfer abilities-reduction of carbonyl compounds was achieved with almost perfect enantioselec-tivily. There is no doubt that, coupled with a proper metal-based hydride-transfer system, such NADH models could perform well in a catalytic version. 

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