Carbonyl compounds deuterium exchange

There have been numerous studies of the rates of deprotonation of carbonyl compounds. These data are of interest not only because they define the relationship between thermodynamic and kinetic acidity for these compounds, but also because they are necessary for understanding mechanisms of reactions in which enolates are involved as intermediates. Rates of enolate formation can be measured conveniently by following isotopic exchange using either deuterium or tritium ... 

The pyridine-catalyzed aromatic proton exchange with deuterium provides a simple indication of the ability of a phenol to participate in chromene formation. Only those phenols which undergo exchange react with the unsaturated carbonyl compound, the attack occurring at the positions of deuteration (64JA2084). 

D—H exchange occurs mainly by way of iminium ion and enamine formation. For these two carbonyl compounds, it was also observed that dedeuteriation by [86] is stereospecific (preferential exchange of the pro-5 c-deuterium relative to that of the pro-/ one). 

We have already seen that exchange of hydrogen for deuterium, movement of double bonds into conjugation, and racemization can occur with enols or enolates as intermediates. These are chemical reactions of a sort, but it is time to look at some reactions that make significant changes to the carbonyl compound. 

The mercury-carbon bond of this bicyclic ketone is fastened almost perpendicularly to the plane of the carbonyl 77-orbital. This perpendicularity may be solely responsible for the fact that the compound, unlike the a-mercurated open-chain 0x0 compounds, possesses a quite inactive mercury atom. While the compounds ClHgCH2C(0)R are instantaneously hydrolyzed or alcoholyzed in the presence of I , and readily react with triphenylchloromethane or with acyl chlorides, a-chloromercuricampheni-lone reacted neither with these agents nor even when refluxed with concentrated hydrochloric acid for a long time. Together with Kursanov, Pecherskaya, and Parnes 121) we studied deuterium exchange in cam-phenilone and camphorquinone... 

Direct homoenolisation of a carbonyl compound with base is not of much practical use. Ketones blocked in the a-position do exchange with deuterium in base, but after five weeks in f-BuOK/ f-BuOD at 185 °C only 3.18 atoms of deuterium had been incorporated into camphor 6 with the distribution shown. The two sites for homoenolisation were responsible for only 0.65 and 0.45 atoms, in contrast to 1.27 atoms at the a and 0.81 at the y atoms.2... 

Only a-hydrogen atoms are exchanged because the reaction occurs through an enolate ion intermediate. All possible enolizable hydrogen atoms are eventually replaced. The hydrogen atoms are lost in the solvent, which contains many more deuterium atoms than the number of hydrogen atoms transferred from the carbonyl compound. 

Studies aimed at the elucidation of reaction mechanisms have been performed by many groups, notably by those of Backvall [28]. In test reactions, typically enantiopure 1-phenylethanol labeled with deuterium at the 1-position (8) is used. The compound is racemized with acetophenone (9) under the influence of the catalyst and after complete racemization of the alcohol, the deuterium content of the racemic alcohol is determined. If deuterium transfer proceeds from the a-carbon atom of the donor to the carbonyl carbon atom of the acceptor the deuterium is retained, but if it is transferred to the oxygen atom of the acceptor it is lost due to subsequent exchange with alcohols in the reaction mixture (Scheme 20.4). 

LiAlH4 as this avoids protonation of the enolate and the production of any over-reduction products. Cholest-4-en-3-one may be reduced to cholestanone (5a 5/8,1 19) with alkali-metal carbonyl chromates. The studies on intramolecular hydride shifts on hydroxy-ketones and -aldehydes have been extended. " The hydride shifts were examined in a number of y- and 5-hydroxy-carbonyI compounds by heating the substrates with alkaline alumina containing D2O. Exchange of protons on the carbon a to both oxygen functions signals the intramolecular hydride shift typically, the hemiacetals (95) and (96) each incorporate up to six deuterium atoms. The general conclusion, in common with literature precedent, is that, whereas 1,5-shifts are common, 1,4-shifts are rare. 

The Clemmensen reduction was accompanied by D/H exchange via acid-catalysed enolization of the carbonyl group, resulting in the production of deuteriated compounds 57 and 58 with various numbers of deuterium atoms. The mixture of the compound 59 obtained by the Wolf-Kishner reduction was predominantly labelled at position 2. This has been proved by the 13C-NMR spectrum. Isotope shift and loss intensivity on substituted C(2) carbon signals have been observed54,55. 

The activation energy for stereoisomerization of metal carbonyl hydrides varies considerably. Complexes possessing the coordination numbers 6 and 4 are generally inert, while compounds which have coordination numbers 5 or higher than 6 are usually stereochemically labile. Because of crucial importance in catalytic processes, the isotopic H-D exchange between hydrido complexes and hydroxyl solvents, deuterium, and olefins is of particular interest. Often, exchange reactions with solvents such as D2O or EtOD are catalyzed by acids and bases. 

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