Rate determining step Stille coupling

The general catalytic cycle for the coupling of aryl-alkenyl halides with alkenes is shown in Fig. 9.6. The first step in this catalytic cycle is the oxidative addition of aryl-alkenyl halides to Pd(0). The activity of the aryl-alkenyl halides still follows the order RI > ROTf > RBr > RC1. The olefin coordinates to the Pd(II) species. The coordinated olefin inserts into Pd—R bond in a syn fashion, p-Hydrogen elimination can occur only after an internal rotation around the former double bond, as it requires at least one /I-hydrogen to be oriented syn perpendicular with respect to the halopalladium residue. The subsequent syn elimination yields an alkene and a hydridopalladium halide. This process is, however, reversible, and therefore, the thermodynamically more stable (E)-alkene is generally obtained. Reductive elimination of HX from the hydridopalladium halide in the presence of a base regenerates the catalytically active Pd(0), which can reenter the catalytic cycle. The oxidative addition has frequently assumed to be the rate-determining step. 

We have used inter- and intramolecular kinetic isotope effects to examine the mechanism of these Lewis acid catalyzed ene reactions. The Lewis acid catalyzed ene reaction has traditionally been though to proceed through either a concerted pericyclic mechanism or a stepwise reaction with a zwitterionic intermediate. We found that the intermolecular isotope effect in the Me2AlQ catalyzed ene reaction of formaldehyde is 1.3 with methylenecyclohexane and methylenecyclohex-ane-2,2,6,6- 4 and 1.4 with 2,3-dimethyl-2-butene and 2,3-dimethyl-2-butene- /i2. Since secondary iotope effects could be responsible for these results, these values are consistent with either a stepwise or concerted mechanism. Intramolecular isotope effects were determined to be 2.9 and 2.7 with 2 and 3, respectively. These substantial intramolecular isotope effects coupled with the small intermolecular isotope effects indicate that the reaction is stepwise with proton transfer following the rate determining step. In an intramolecular competition such as the ene reactions of formaldehyde with 2 and 3 an isotope effect will still be observed if the hydrogen transfer occurs... 

Determination of III is based upon the different rate at which the coupled reaction to the first reduction step takes place for I and III (or II). Under the same experimental conditions, the voltammogram of I shows no anodic peak, while that of III still shows the reoxidation of remaining adsorbed 5,8-dihydroneopterin. This fact is exploited analytically, and this peak (Illia) is used for the joint determination of III and II, under the assumption that they behave exactly the same way. 

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