Vinylcyclopropane Rearrangement - Mechanism

Mechanism

The mechanistic discussion on whether the vinylcyclopropane rearrangement proceeds through a diradical-mediated two-step or a fully concerted orbital-symmetry-controlled mechanism has been going on for more than half a century. Kinetic data together with the secondary kinetic isotope effects observed at the vinyl terminus of the vinylcyclopropane suggest a concerted mechanism whereas product distribution indicates a stepwise-diradidal mechanism. In the 1960s, shortly after the rearrangement was discovered, it was established that the activation energy for the vinylcyclopropane rearrangement is around 50 kcal/mol. The kinetic data obtained for this rearrangement were consistent with a concerted mechanism where cleavage of the cyclopropyl carbon-carbon bond was rate-limiting. Albeit a concerted mechanism seemed likely it was shortly recognized that the activation energy to break the carbon-carbon bond in unsubstituted cyclopropane was with 63 kcal/mol exactly 13 kcal/mol higher in energy than the parent activation energy, a difference remarkably similar to the resonance energy of the allyl radical. Immediately people started to appreciate the possibility for a diradical intermediate arising from homolytic cleavage of the weak C1-C2-cyclopropane bond under thermal conditions.

The discussion on whether the vinylcyclopropane rearrangement proceeds via a fully concerted or a two-step, non-concerted mechanism was given further careful consideration when Woodward and Hoffmann used the vinylcyclopropane rearrangement to exemplify -sigmatropic concerted alkyl shifts in 1969. They hypothesized that if a concerted mechanism was operative the consequences of orbital-symmetry controlled factors would only allow the formation of certain products. According to their analysis of a vinylcyclopropane substituted with three R groups the antarafacial -shift of bond 1,2 to C-5, with retention at C-2, leading to the ar cyclopentene and the suprafacial -shift of bond 1,2 to C-5, with inversion at C-2, leading to cyclopentene si are symmetry allowed whereas the suprafacial -shift of bond 1,2 to C-5, with retention at C-2, leading to cyclopentene sr and the antarafacial -shift of bond 1,2 to C-5, with inversion at C-2, leading to the ai cyclopentene are symmetry-forbidden. It is important to note that Woodward and Hoffmann based their analysis solely on the principles of the conservation of orbital symmetry theory without however making any mechanistic or stereochemical prediction.

The attention directed towards the vinylcyclopropane rearrangement by Woodward and Hoffmann as a representative example for -carbon shifts clearly enhanced the interest in this reaction. Furthermore their analysis revealed potential experiments that would allow to distinguish between a concerted or stepwise mechanism. The stereochemical consequences of a concerted reaction pathway on the reaction outcome suggested an experiment where one would correlate the obtained reaction stereochemistry with the predicted reaction stereochemistry for a model substrate. Observing the formation of ai- and sr-cyclopentene products would support the notion that a stepwise, non-concerted mechanism is operative whereas their absence would point towards a fully concerted mechanism. As it turned out finding an appropriate substituted model substrate to study the stereochemical outcome of the vinylcyclopropane rearrangement was much more challenging than initially thought since side reaction such as the homodienyl -hydrogen shift]]s and more so thermal stereomutations tend to scramble stereochemical distinctions much faster than rearrangements lead to the cyclopentene products.

Even though deconvolution of the complex kinetic scenarios underlying these rearrangements was difficult there have been several studies reported where exact and explicit deconvolutions of kinetic and stereochemical raw data to account for the stereochemical contributions arising from competitive stereomutations was possible.

Thereby rate constants for all four stereochemically distinct pathways of the vinylcyclopropane rearrangement could be determined.

The data clearly indicated that the mechanistic preferences of the rearrangements are system dependent. Whereas trans-vinylcyclopropanes tend to form more of the symmetry-allowed ar- and si-cyclopentenes supportive of a concerted mechanism, the cis-vinylcyclopropanes preferentially yield the symmetry-forbidden ai- and sr- products suggesting a more stepwise, diradical mechanism. The influence of substituent effects on the reaction stereochemistry also becomes apparent from the data. Substituents with increased radical stabilizing ability not only lower the rearrangements activation energy but also reclosure of the initially formed diradical species becomes slower relative to the rate of cyclopentene formation resulting in an overall more concerted mechanism with less stereomutation (e.g. entry 6 & 7). In all cases though all the four products were formed indicating that both orbital-symmetry controlled pericyclic, as well as diradical-mediated two-step mechanisms are operative either way. The data is consistent with the formation of biradical species on a relatively flat potential energy surface allowing for restricted conformational flexibility before the products are formed. The amount of conformational flexibility and therefore conformational evolution accessible to the diradical species before forming product depends on the constitution of the potential energy surface. This notion is also supported by computational work. One transition state with a high diradicaloid character was found. Following the potential energy surface of the lowest energy path of the reaction it was found that a very shallow regime allows the diradical species to undergo conformational changes and stereoisomerization reactions with minor energetic consequences. Furthermore it was shown that substituents can favor stereoselective pathways by destabilizing species that allow stereochemical scrambling.