Isotopic labelling studies ring opening

The acetylene-insertion reaction presumably occurs by the following mechanistic sequence (1) insertion of Pd(0) into the SCB, (2) regioselective yy -silylpalladation of the acetylenic compounds to provide seven-membered l-pallada-4-silacyclic intermediate, and (3) reductive elimination of Pd(0) to afford silacyclohexene. Alternatively, /3-hydride elimination would open the palladacycle, generating a vinylpalladium hydride species that would undergo reductive elimination to yield the ring-opened allylvinylsilane. Isotopic labeling studies provided evidence in support of this mechanistic hypothesis (Scheme 47). 

The proof that the C=C bond was itself being broken in these reactions was provided by isotopic labelling studies, first by Calderon in 1967 for the exchange reaction of but-2-ene [7,8], eq. (2), then by Boelhouwer (1968) for the reaction of propene [9], eq.(3), and later by DallAsta in 1971 for the ring-opening copolymerization of [1- C]cyclopentene with unlabelled cyclooctene [10]. 

Below — 140°C, the EPR spectrum observed was that of the cyclopropylmethyl radical. If the photolysis was done above — 140°C, however, the spectmm of a second species was seen, and above — 100°C, this was the only spectmm observed. This second spectmm could be shown to be that of the 3-butenyl radical. This study also established that the 3-butenyl radical did not revert to the cyclopropylmethyl radical on being cooled back to — 140°C. The conclusion is that the ring opening of the cyclopropyl radical is a very facile process and that the lifetime of the cyclopropyl radical above — 100°C is very short. Even though the equilibrium favors the 3-butenyl radical, the reversible ring closure can be detected by isotopic labeling experiments, which reveal the occurrence of deuterium migration ... 

Wentrup and co-workers have carried out systematic flash vacuum thermolysis studies with a series of fused tetrazoles. Investigations of the isomeric tetrazolo[l,5- ]pyrazine 17 and tetrazolo[l,5-f]pyrimidine 20 showed that, in both cases, ring contraction takes place to afford imidazoles in high yields, but isotope labeling experiments revealed that the mechanisms of the openings of the two ring systems are different <2002JOC8538>. 

Isotope labelling again proved (21) that the decarboxylation involves only carbon 2 of the oxazolidine-2,5-dione, and studies of the kinetic isotope effect (22) demonstrated that this step is not the rate-determining in the overall process. Therefore, the rate of the overall reaction is determined either by (a) — the formation of the complex, or by (b), viz. by opening of the ring between atoms 1 and 5. This conclusion applies also to the "normal amine-propagated NCA polymerisation. 

Baillie, T.A. et al., Mechanistic studies on the reversible metabolism of rofecoxib to 5-hydroxyrofecoxib in the rat Evidence for transient ring opening of a substituted 2-furanone derivative using stable isotope-labeling techniques, Drug Metab. Dispos., 29(12), 1614, 2001. 

Although the reaction mechanism has been studied via an isotopic labeling experiment, the proposed mechanism is still not clear. Thus a revised and tentative mechanism is displayed here. In this mechanism, the initial addition of an amido nitrogen to the iminium ion eliminates the charge, but the protonation of nitrogen increases the ring strain, and the three-membered ring opens. 

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