Intramolecular hydrogen-deuterium

Song, Z. Beak, P. Investigation of the mechanisms of ene reactions of carbonyl enophiles by intermolecular and intramolecular hydrogen-deuterium isotope effects Partitioning of reaction intermediates, J. Am. Chem. Soc. 1990,112, 8126-8134. 

Of interest also is the intramolecular hydrogen-deuterium exchange invoked to explain the reactions depicted in equation [93] (262). Reactions of complexes 174 and 175 led to an equimolar mixture of complexes 176 and 177 indicating that these two compounds are in equilibrium. An intermolecular exchange has been rejected on the basis of the findings shown in equation [94]. The above exchange thus occurs within the coordination sphere of manganese and does not involve formation of free hydrosilane by a reductive elimination process. The... 

Of interest also is the intramolecular hydrogen-deuterium exchange invoked to explain the reactions depicted in equation 1978. The reactions of hydrido and deuterio... 

Hittle, L.R., Proctor, A., and Hercules, D.M., Investigation of intramolecular hydrogen-deuterium exchange in the time-of-flight secondary-ion mass spectra of polystyrene. Macromolecules, 28, 6238, 1995. 

The efficiency of reduction of benzophenone derivatives is greatly diminished when an ortho alkyl substituent is present because a new photoreaction, intramolecular hydrogen-atom abstraction, then becomes the dominant process. The abstraction takes place from the benzylic position on the adjacent alkyl chain, giving an unstable enol that can revert to the original benzophenone without photoreduction. This process is known as photoenolization Photoenolization can be detected, even though no net transformation of the reactant occurs, by photolysis in deuterated hydroxylic solvents. The proton of the enolic hydroxyl is rapidly exchanged with solvent, so deuterium is introduced at the benzylic position. Deuterium is also introduced if the enol is protonated at the benzylic carbon by solvent ... 

Mixtures of EE Cl and [EMIMjCl have also been studied [9, 10]. By analysis of the first order differences by hydrogen/deuterium substitution both on the imidazoli-um ring and the EE Cl, two intramolecular peaks were observed. These indicated the presence of [EECI2] as an asymmetric species, which, coupled with analysis of the second order differences, allowed the structure in Figure 4.1-3 to be proposed. 

Early experiments [1] using (+)-apopinene and deuterium showed, however, that in the isomerized molecules the deuterium content was very low and the isomerization was much faster than deuterium incorporation into the allylic position. Therefore it seemed probable that isomerization takes place through an intramolecular hydrogen shift. A sigmatropic 1,3-hydrogen shift was suggested, in which the allylic endo-H shifted top shift) [2]. 

Measurements of the deuterium isotope effect for unsymmetrical di-Schiff bases fully confirmed the interrelation between proton transfer equilibria in both intramolecular hydrogen bonds.46... 

Song and Beak161 have used intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects to investigate the mechanism of the tin tetrachloride catalysed ene-carbonyl enophile addition reaction between diethyloxomalonate and methylenecy-clohexane (equation 105). These ene reactions with carbonyl enophiles can occur by a concerted (equation 106) or a stepwise mechanism (equation 107), where the formation of the intermediate is either fast and reversible and the second step is slow k- > k-i), or where the formation of the intermediate (the k step) is rate-determining. 

Song and Beak found intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects of 1.1 0.2 and 1.2 0.1, respectively, for the tin tetrachloride catalysed ene reaction. Since significant intramolecular and intermolecular primary deuterium kinetic isotope effects of between two and three have been found for other concerted ene addition reactions161, the tin-catalysed reaction must proceed by the stepwise pathway with the k rate determining step (equation 107). 

For Rh(I)/BINAP-catalyzed isomerizations of allylic amines, the mechanistic scheme outlined in Eq. (2) has been proposed. The available data are consistent with the notion that Rh(I)/PF-P(o-Tol)2-catalyzed isomerizations of allylic alcohols follow a related pathway [11]. For example, the only deuterium-containing product of the reaction depicted in Eq. (9) is the l,3-dideuterated aldehyde, which estabhshes that the isomerization involves a clean intramolecular 1,3-migration. The data illustrated in Eqs. (10) and (11) reveal that the catalyst selectively abstracts one of the enantiotopic hydrogens/ deuteriums alpha to the hydroxyl group. 

The relative contribution of the two mechanisms to the actual isomerization process depends on the metals and the experimental conditions. Comprehensive studies of the isomerization of n-butenes on Group VIII metals demonstrated179-181 that the Horiuti-Polanyi mechanism, the dissociative mechanism with the involvement of Jt-allyl intermediates, and direct intramolecular hydrogen shift may all contribute to double-bond migration. The Horiuti-Polanyi mechanism and a direct 1,3 sigma-tropic shift without deuterium incorporation may be operative in cis-trans isomerization. 

According to deuterium-induced upfield H NMR isotope shifts in partially deuterated rigid cyclohexane-1,3-diols dissolved in CDC13 or benzene-c/6, the OH is preferentially solvent-exposed, while deuterium prefers to reside in the intramolecular hydrogen bond (49).121 In acetone-c/6 and DMSO-c/6 downfield isotope shifts indicate that the OH preferentially resides in the intramolecular hydrogen bond, while OD forms an external hydrogen bond to the acceptor solvent, S (50). 

In contrast, a partially deuterated rigid 1,4 diol shows upfield isotope shifts not only in CDC13 but also in acetone- and DMSO-i/fr 122 Again the OH is preferentially solvent-exposed in CDC13, while deuterium prefers to reside in the intramolecular hydrogen bond. Again the OD is preferentially solvent exposed in acetone- and DMSO-d6, while OH prefers to reside in the intramolecular hydrogen bond. The paradoxical commonality of upfield isotope shifts is due to a reversal of the chemical shifts of interior and exterior sites of 1,4 diols in acceptor solvents. The equilibrium constant in DMSO-d6 is... 

Figure 6.17. Arrhenius plot of the rate constant for intramolecular hydrogen (upper trace) and deuterium (lower trace) transfer in the lowest triplet state of compound (6.20) in three different solvents 3-methylpentane (A), its 1 1 mixture with isopentane (O), and a 2 1 1 mixture of both with methylcyclopentane ( ). (From Al-Soufi et al. [1991].)...

Next reviews were dedicated to problems of hydrogen-bonded systems. Hydrogen/deuterium isotope effects on NMR parameters in liquids and solids have been reviewed by Limbach et al.11 Review covers period to 2004 and illustrates the correlation of intermolecular hydrogen-bonded systems geometry and H/D isotope shifts and coupling constants, particularly measured in the solid state and in liquids at low temperature. Several reviews concern the isotope effects on intramolecular hydrogen-bonded systems.12-17 Since that time several new papers dedicated to hydrogen-bonded systems were published, mostly on intramolecular systems.18-24... 

Fig. 18. The expected percentages of various labelled products of the dioldehydratase reaction using 25 as substrate. The calculation was based on the following facts and assumptions (1) The enzyme does not differentiate between the enantiotopic hydrogen positions (conclusion from experiments with species 17 and 18 shown in Fig. 14) (2) in the competition between vicinal hydrogen atoms there is an intramolecular kinetic deuterium isotope effect of 2.6 (Fig. 15) (3) this effect is 10 for geminal hydrogen atoms (4) the migrating hydroxyl group substitutes one of the hydrogen atoms in the vicinal position stereospecifi-cally (i.e., with inversion).

Reuben J (1986) Intramolecular hydrogen bonding as reflected in the deuterium isotope effects on carbon-13 chemical shifts. Correlation with hydrogen bond energies. J Am Chem Soc 108 1735-1738... 

Altman, L. J., Lauggani, D., Gunnarsson, G., and Wennerstrom, H., Proton, deuterium, and tritium nuclear magnetic resonance of intramolecular hydrogen bonds. Isotope effects and the shape of the potential energy function, J. Am. Chem. Soc. 100, 8264-8266 (1978). 

---