Intramolecular and Intermolecular Kinetic Isotope Effects (KIE) in the Nitrosoarene Ene Reaction:  Experimental Evidence for Reversible Intermediate Formation

The intramolecular and intermolecular kinetic isotope effects (KIE) have been determined for the nitrosoarene ene reaction with deuterium-stereolabeled 2,3-dimethyl-2-butenes (TME). <i>trans</i>-TME<i>-d</i><sub>6</sub> (<i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 3.0) and <i>gem</i>-TME<i>-d</i><sub>6</sub> (<i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 4.0) show large intramolecular primary isotope effects. In contrast, the intramolecular competition in <i>cis-</i>TME<i>-d</i><sub>6</sub> (<i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 1.5) and the intermolecular competition for the TME-<i>d</i><sub>0</sub>/TME-<i>d</i><sub>12</sub> pair (<i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 1.98) show considerably smaller, but mechanistically significant kinetic isotope effects. The latter fact is rationalized in terms of reversible formation of a three-membered-ring intermediate, namely the aziridine <i>N</i>-oxide, or a similar unsymmetrical, polarized diradical in the first step of the reaction. Such reversibility has also been implied earlier for triazolinedione (TAD) and singlet oxygen (<sup>1</sup>O<sub>2</sub>) with deuterium-stereolabeled 2-butenes, but of the three enophiles, ArNO is the most sensitive toward reversibility, which is due to its moderate reactivity and its high steric demand.