kinetics of the reaction were readily simulated [8] by the use of two simple models, one (see A, Scheme 1) that follows the conventional mechanism in which the product catalyzes the addition of the enolate 3 to the aldehyde 4, and the second (see B, Scheme1) in which the product catalyzes a ratelimiting breakdown of the zwitterionic intermediate 5, for example, by proton transfer.

The two mechanistic scenarios (A and B) can, in principle, be distinguished on the basis that upon employing αdeuterated acrylate (2-[2H1]-1;= d1-1), a primary KIE should be completely absent in A but evident in B prior to the autocatalyzed breakdown of zwitterion 5 becoming more efficient than its generation. As the latter condition might only be fulfilled very early in the reaction, the comparison of absolute rates over a number of half-lives, as performed by Isaacs and co-workers with deuterated (> 99%) acrylonitrile,[4a] is unlikely to be informative. In fact, a competition experiment between d-1 and 1 would clearly identify the RLS because we would expect a primary KIE to increase the mole fraction of d-1 in the acrylate (xd-1) if step 3 is rate-limiting and a secondary KIE to decrease xd-1 if step 2 is rate-limiting.[9] We thus analyzed the effect of C (2)-deuteration by 1H NMR spectroscopic analysis of the BHR of approximately equimolar mixtures of d-1 and 1 (xd-1= 0.505 Æ 0.005, Figure 1). As evident from Figure 1b, in the early stages of reaction (up to% 20% conversion), the mole fraction of d-1 increases substantially. As reaction proceeds further into the phase where autocatalysis is by far the dominant process, the ratio then stabilizes (xd-1max= 0.55).[9] This shows that in the early phase (< 20% conversion), step 3 is rate-limiting (primary KIE evident). By using model B as a starting point, we were able to simulate the kinetics of the competition experiments;[8, 9] for example, see the comparison of the predicted (lines) and observed (circles) kinetics in Figure 1, graphs a and c. For satisfactory simulation, the model required incorporation of a substantial primary KIE (kH/kD= 5 Æ 2) for the noncatalyzed step 3. The fact that the simplification of kH/kD= 1 for autocatalysis of step3 allows a satisfactory simulation suggests that the autocatalysis causes a change in the RLS from step 3 to step 2 early in the reaction.[9]