Mechanistic studies, hydrogen isotope

Among the classic methods for the extension of the aldose chain by one carbon atom from the reducing end [9J, the Kiliani-Fischer cyanohydrin synthesis [10] is a milestone in carbohydrate chemistry. However after 110 years from discovery and numerous applications [11], including the preparation of carbon and hydrogen isotopically labeled compounds for mechanistic and structural studies [12], there are still several drawbacks that make the method impractical. These are the low and variable degree of selectivity and the harsh reaction conditions that are required to reveal the aldose from either the aldonic acid or directly from the cyanohydrin. Synthetic applications that have appeared in recent times confirmed these limitations. For instance, a quite low selectivity was registered [13] in the addition of the cyanide ion to the D-ga/acfo-hexodialdo-l,5-pyranose derivative 1... 

Exact localization of the hydrogen isotope is usually required, and it is inadvisable to rely on the method of synthesis, as the label is not always situated entirely at the position predicted.69 In many mechanistic and biological studies with enzymes, the position of the label alters during the reaction, and, in others, where a proton isotope from the solvent is incorporated, it is important to localize the incorporated isotope, and, if it is at a methylene group, to determine its stereochemistry. 

Most of the sugars specifically labeled with isotopes of hydrogen that have been synthesized were prepared for use in mechanistic studies of enzymes. 

The hydrogenation of molecules of the type HC =CR, where R is an alkyl group, is a largely neglected field. The only mechanistic studies reported to date are the hydrogenation of propyne in the gas phase (78) and of 1-butyne (a) in alcoholic solution (57) and (b) in the gas phase (90). Only the last mentioned study has employed an isotopic tracer. 

Deuterium (and tritium) labelled compounds are not only useful for mechanistic studies but valuable information concerning both ground state and excited state properties of molecules has been obtained by the use of compounds containing isotopes of hydrogen. 

Mechanistic studies of other reactions of the silanes include the methoxide-catalysed methanolysis of triphenylsilane. Solvent isotope effects in mixtures of methanol and 0-deuteriomethanol suggest a transition state with two solvent molecules with stronger hydrogen bonds than in the bulk solvent, in addition to the proton-donor methanol molecule. Another isotopic study of this type of reaction is interpreted as the rapid reversible formation of a five-co-ordinate silicon intermediate, followed by a rate-determining cleavage of the Si—H bond, with a bent Si - -H "H geometry in the transition state. 

Mechanistic studies of Ru-catalyzed asymmetric hydrogenations and transfer hydrogenations began shortly after the discovery of catalysts 1 and 2 and were based on three main approaches stoichiometric NMR studies, kinetic analyses including measurements of kinetic isotope effects (KlE s), and gas-phase computations. All of these methods are indeed ubiquitously used by chemists to study reaction mechanisms and analyze catalytic cycles. 

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