Primary deuterium kinetic isotope

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). 

These reactions proceed through symmetrical transition states [H H H] and with rate constants kn,HH and kH,DH, respectively. The ratio of rate constants, kH,HH/kH,DH> defines a primary hydrogen kinetic isotope effect. More precisely it should be regarded as a primary deuterium kinetic isotope effect because for hydrogen there is also the possibility of a tritium isotope effect. The term primary indicates that bonds at the site of isotopic substitution the isotopic atom are being made or broken in the course of reaction. Within the limits of TST such isotope effects are typically in the range of 4 to 8 (i.e. 4 < kH,HH/kH,DH < 8). 

Pyrazolines have been used as models of intramolecular dyotropy (87T5981, 93JCS(P2)l2li). By combining primary deuterium kinetic isotope effects and X-ray crystallography, polycyclic systems, like (426), were shown to undergo a double proton transfer to (427). 

Ab initio density functional calculations have been applied to dimethyhiitramine decomposition in order to calculate the primary deuterium kinetic isotope effect (kH/km =4.21) for HONO elimination Me2NN02 - [TS] - CH2NMe + N02H and the secondary isotope effect (kH/kD6 = 1.4) for N—N bond homolysis, each at 240 °C.64 Since the experimentally observed isotope effect is 1.57, it has been concluded that the latter process may be rate determining. 

In contrast, reaction of electron acceptor-substituted phenols exhibits p = +1.72, indicating the development of negative charge at the phenolic oxygen in the rate-determining step for reaction of relatively acidic, weakly nucleophilic phenols with 110, and the addition of 112f exhibits a large primary deuterium kinetic isotope effect of k /kv = 5.3. This is consistent with the electrophilic addition mechanism of equation 85, in which full or partial protonation at silicon precedes nucleophilic attack. 

Primary deuterium kinetic isotope effects have always been observed, ruling out their use as a mechanistic tool to distinguish between the two possibilities. The different behavior observed with these systems can be explained on the basis of the... 

At high pH, both oc-and p-NeuNAcOAr liberate ArO by a base-catalysed process which, however, shows only a weak dependence on the of ArOH P K —0.2), is not subject to a primary deuterium kinetic isotope effect at C3, and does not result from nucleophilic attack on the aromatic ring, as shown by 0 labelling. A possible, though far from proven, mechanism, is that of Figure 3.26. 

The well-known oxidations of primary and secondary alcohols with Cr species proceed through chromate esters. The definitive mechanistic expeii-ments " demonstrating that previously observed chromate esters were indeed on the reaction pathway showed that either formation or decomposition of the ester could be rate-determining. The rates of oxidation of cyclohexanol and the secondary hydroxyl group of a very steiically hindered steroid in aqueous acetic acid were measured as a function of the solvent composition. The former increased radically as the acetic add concentration increased whereas the latter remained invariant. The former exhibited a primary deuterium kinetic isotope effect of 5, whereas there was no KIE on the oxidation of the crowded steroid. Therefore, the rate-determining step in the oxidation of the cyclohexanol was decomposition of the chromate ester and in the oxidation of the steroid it was its formation, with the ester an obligate intermediate in both reactions. 

Scheme 9 Initial expectation of a normal primary deuterium kinetic isotope effect due to ground state energy differences.

Okamura determined the primary deuterium kinetic isotope effect in a vitamin D-like model system as a function of temperature to obtain d - h = 1. 62 kcal/mol and Ah/Ad = 0.835 (Scheme 7.56). These results suggest a normal primary KIE without tunneling, not unlike those determined by Roth for the 1,5-hydrogen shift in cw-l,3-pentadiene (see Chapter 6, Section 2). 

To study the stereochemistry of the hydrogen shift, optically active 1-deuterio-l-methyl-3- r -butylindene was found to give l- r -butyl-3-methylindene = 5.5) with optical and deuterium labeling consistent with a suprafacial deuterium shift (Scheme 10.4). Moreover, the primary deuterium kinetic isotope effect was roughly 3. 

---