Computational Study and Analysis of the Kinetic Isotope Effects of the Rearrangement of cis-Bicyclo[4.2.0]oct-7-ene to cis,cis-Cycloocta-1,3-diene Carlos Silva Lo ´ pez, Olalla Nieto Faza, and A Ä ngel R. de Lera* Departamento de Quı ´mica Orga ´ nica, Facultade de Quı ´mica, UniVersidade de Vigo, Lagoas-Marcosende, E-36310, Vigo, Galicia, Spain qolera@uVigo.es Received February 22, 2006 ABSTRACT On the basis of KIE experiments, the ring opening of cis-bicyclo[4.2.0.]oct-7-ene has been suggested as an anti-Woodward-Hoffmann reaction candidate. We hereby report the results of a high-level computational study of the alternate reaction pathways which proves that the energy profiles show a clear preference for the conrotatory (W-H allowed) ring opening followed by double-bond isomerization. Computed KIE values for the aforementioned mechanism are in good agreement with the experimental values. The thermal ring-opening reaction of cis-bicyclo[4.2.0]oct- 7-ene 1 to cis,cis-cycloocta-1,3-diene 5 has been a mecha- nistic enigma for decades. Very recently, Baldwin and co- workers conducted a thorough study aimed to provide a definitive answer to such a stimulating question. 1 Three candidate mechanisms (transition-state numbering in paren- theses) were considered for this rearrangement (see Figure 1): (i) A disrotatory ring opening (2 disrot ). (ii) A conrotatory ring opening (2 conrot ) to 3 followed by a [1,5] H sigmatropic shift (4 [1,5]-H ). (iii) A conrotatory ring opening (2 conrot ) to 3 followed by a double-bond isomerization (4 dbi ). Baldwin collected then a complete set of Arrhenius parameters of the potential steps describing the reaction and performed a number of KIE experiments devised to rule out the involvement of a [1,5] H sigmatropic shift or a double- bond isomerization. The latter experiments seemed to confirm that none of the possible evolutions of a cis,trans- cycloocta-1,3-diene 3 intermediate are participating in the reaction mechanism. In this paper, however, Baldwin rec- (1) (a) Baldwin, J. E.; Gallagher, S. S.; Leber, P. A.; Raghavan, A. Org. Lett. 2004, 6, 1457. (b) Baldwin, J. E.; Gallagher, S. S.; Leber, P. A.; Raghavan, A.; Shukla, R. J. Org. Chem. 2004, 69, 7212. Figure 1. Mechanistic alternatives for the ring opening of cis- bicyclo[4.2.0]oct-7-ene 1. ORGANIC LETTERS 2006 Vol. 8, No. 10 2055-2058 10.1021/ol060465f CCC: $33.50 © 2006 American Chemical Society Published on Web 04/21/2006