Asymmetric deuterium-labeling studies

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

Asymmetric cyclization was also successful in the rhodium-catalyzed hydrosilylation of silyl ethers 81 derived from allyl alcohols. High enantioselectivity (up to 97% ee) was observed in the reaction of silyl ethers containing a bulky group on the silicon atom in the presence of a rhodium-BINAP catalyst (Scheme 23).78 The cyclization products 82 were readily converted into 1,3-diols 83 by the oxidation. During studies on this asymmetric hydrosilylation, silylrhodation pathway in the catalytic cycle was demonstrated by a deuterium-labeling experiment.79... 

In a different ongoing study, a Bacillus subtilis lipase has been chosen as the catalyst in the asymmetric hydrolysis of the meso-diacetate 11 with formation of enantiomeric alcohols 12 (Fig. 11.19) [82]. This reaction does not constitute kinetic resolution and can thus be carried out to 100 % conversion. Screening is possible on the basis of the ESI-MS system [50] (see above) using the deuterium labeled pseudo-meso substrate 13 (Fig. 11.20). The ratio of the two pseudo-enantiomeric products 14 and 15 can easily be determined by integrating the two appropriate MS peaks. 

Another recent application of high resolution NMR was to study the reaction mechanism of the solvolysis of norbornen-2-yl derivatives (7) The acetolysis of the mono-deuterium compound 1, [2-d] exo-5-norbornen-2-yl brosylate, for instance led to the products to 5. The deuterium label distribution of these products was determined unambiguously (Figure 6) and thus allowed the elimination of a previously proposed mechanism which required the intervention of asymmetrical homoallyllc cation intermediates. 

It would be well to point out a few examples which illustrate the overlap of asymmetric reduction studies and molecular biochemistry. Diphosphopyridine nucleotide (DPN) and triphospho-pyridine nucleotide (TPN) are important coenzymes in biochemical oxidation reduction reactions. Certain enzymes function as catalysts for the reversible transfer of hydrogen between these nucleotides and a substrate for which the enzyme is specific. For example, DPN and the enzyme, alcohol dehydrogenase (ADH), form a redox system with ethanol. Using deuterium labeled reducing agent and substrate, Westheimer, Vennesland,... 

We used such an approach in the study of dissociative edep reduction of the p, y-unsaturated alcohols. Specially synthesized deuterated 2,4-pentadienol and its derivatives CH2=CHCH=CHCD2Y, where Y = -OH, -OAc, and -OMe, was taken as a substrate RY [272,273] the deuterium label is necessary to distinguish the 1,5-positions. In contrast to the cases studied earlier (cinnamic alcohol, vitamin A, etc.. Sect. 9.2.2, Natural Polyenes Vitamins A and D, Carotenes, and Porphyrins ), the reaction proceeds here via the symmetric pentadienyl anion [CH2-CH-CH-CH-CD2]. Therefore, two piperylene isomers CH3-CH=CH-CH=CD2 (a) and CH2=CH-CH=CH2-CD2H (h) in the strictly equal amounts could be anticipated as products. However, the preferential formation of one isomer, with the rexp= [a]/ m > 2, was found experimentally. This anomaly was explained by nonequUibrium asymmetric arrangement of anion near the electrode due to the orientation inheritance of the original asynunetric molecule RY. This should lead to the intra-anion... 

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