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Abstract: cis,anti,cis-Tricyclo[7.4.0.0^2,8]tridec-10-ene (13TCT) undergoes [1,3] sigmatropic rearrangements to the si product 1 and to the sr product 2 with si/sr = 2.1 at 315 ¼C in the gas phase. However, the dominant isomerization process is epimerization at  C8 to give product 3. That stereomutation occurs 50% faster than the si and sr shifts combined.

The theoretical paradigm for thermal sigmatropic reactions enunciated by Woodward and Hoffmann in The Conservation of Orbital Symmetry provided guidance on mechanistic and stereochemical expectations.¹  For [1,3] carbon shifts such as vinylcyclobutane-to-cyclohexene isomerizations, they would, according to the rubric, take place with symmetry-allowed si (suprafacial, inversion) and ar (antarafacial, retention) stereochemical outcomes, if formed through concerted paths, and not give symmetry-forbidden sr (suprafacial, retention) and ai (antarafacial, inversion) products unless non-concerted reactions were involved.

Thermal isomerizations  of chiral trans-1,2-divinyl- and 1,2-dipropenylcyclobutanes were studied by Berson and Dervan in 1973.² All four possible stereochemical outcomes as these monocyclic vinylcyclobutanes formed isomeric cyclohexenes were evident in product mixtures.  The suprafacial paths were preferred, with si/sr ratios >1.  Antarafacial stereochemical paths were relatively minor, but they were detected.  Given the geometric constraints inherent in most bicyclic vinylcyclobutanes, [1,3] carbon shift reactions cannot give antarafacial products.  Only  symmetry-allowed si and symmetry-forbidden sr products might be formed, at different rates. Experimentally determined si/sr ratios would afford  stereoselectivity and mechanistic distinctions between concerted and diradical-mediated routes for [1,3] shifts of bicyclic vinyl-cyclobutanes.   The si/sr ratio became a default standard for assessing the degree of concert for these sigmatropic reactions.

Thermal reactions of bicyclo[3.2.0]hept-2-enes³ and bicyclo[4.2.0]oct-2-enes⁴ revealed some stark differences with respect to product stereoselectivity and preferred exit channels. The si/sr ratios are larger for bicyclo[3.2.0]hept-2-enes³ than for bicyclo[4.2.0]oct-2-enes,⁴ systems of greater conformational flexibility.  Compared to the strong preference for [1,3] shifts favored by bicyclo[3.2.0]hept-2-enes,  bicyclo[4.2.0]oct-2-enes exhibit dramatically different thermal behavior.  The dominant rearrangement mode for bicyclo[4.2.0]oct-2-enes at 275 ¼C leads to a one-centered stereomutation, an epimerization, at C8.  The next most prominent thermal process is fragmentation.  The [1,3] carbon migrations, only marginally stereoselective, are least important. 

In order to examine conformational mobility at the migrating carbon on [1,3] shifts, we have studied a series of three tricyclic vinylcyclobutanes, labeled by the  acronyms  11TCU, 12TCD, and 13TCT, combining the number of carbons involved, the common tricyclic designation (TC), and the initial for the olefinic name.     Each of the three contains a common bicyclo[4.2.0]oct-2-ene core; they differ only in the ring size in which the migrating carbon resides: the tricyclics have 5, 6-, and 7-membered rings fused with the bicyclo[4.2.0]oct-2-ene substructure.   As shown in Table 1, 11TCU is restricted to a symmetry-forbidden sr migration^5a whereas 12TCD undergoes a [1,3] shift with si/sr = 2.4.^5b

Table 1.  Stereochemistry of [1,3] Shifts for 4 and Tricyclic Vinylcyclobutane Analogs

The 13TCT reactant leads to [1,3] shifts in a si/sr  ratio of 2.1 (Table 1), a value comparable to that for 12TCD. The thermal profile of 13TCT, however, is quite distinct compared to the other two tricyclic vinylcyclobutanes in that the major thermal isomerization process involves an epimerization at C8, not [1,3] sigmatropic rearrangements. While 13TCT mimics the bicyclo[4.2.0]oct-2-enes in this regard, fragmentation is only a minor thermal pathway for 13TCT unlike the product distribution shown by exo-8-methylbicyclo-[4.2.0]oct-2-ene (4), as seen in Table 2.

Table 2.  Exit Channels for 4 and Tricyclic Vinylcyclobutane Analogs

Impact of the Research

The present study of 13TCT is the third variation of a tricyclic vinylcyclobutane with a bicyclo[4.2.0]oct-2-ene core.  Our recent work on bicyclo[4.2.0]oct-2-enes and their tricyclic analogs has been a very productive period for the PI with respect to undergraduate student research productivity and subsequent publication of the undergraduate research.  A manuscript on the 13TCT research will be submitted for publication.

Two F&M undergraduate students, Drew Bogdan and Dave Powers, were coauthors of the two prior tricyclic vinylcyclobutane papers (references 5a and 5b).  Drew Bogdan received his Ph.D. from Cornell and is currently in a postdoctoral position at Scripps.  Dave Powers should complete his Ph.D. at Harvard this year and is in the process of applying for postdoctoral appointments.  One former F&M students and four current F&M students are coauthors on the 13TCT manuscript.  Two of the current students intend to pursue a graduate degree in chemistry; the other two students will apply to medical school.

References

(1) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital Symmetry; Verlag Chemie: Weinheim, 1970.

(2) Berson, J. A.; Dervan, P. B. J. Am. Chem. Soc.  1973, 95, 267-269; 269-270.

(3) Leber, P. A.; Baldwin, J. E.  Acc. Chem. Res.  2002, 35, 279-297.

(4) (a) Bogle, X. S.; Leber, P. A.; McCullough, L. A.; Powers, D. C.  J. Org. Chem.  2005, 70, 8913-8918.  (b)  Baldwin, J. E.; Leber, P. A.; Powers, D. C.  J. Am. Chem. Soc.  2006, 128, 10020-10021. (c) Powers, D. C.; Leber, P. A.; Gallagher, S. S.; Higgs, A. T.; McCullough, L. A.; Baldwin, J. E.  J. Org. Chem.  2007, 72, 187-194. (d) Leber, P. A.; Lasota, C. C.; Strotman, N. A.; Yen, G. S. J. Org. Chem.  2007, 72, 912-919.

(5) (a) Baldwin, J. E.; Bogdan, A. R.; Leber, P. A.; Powers, D. C.  Org. Lett.  2005, 7, 5195-5197. (b)  Leber, P. A.; Bogdan, A. R.; Powers, D. C.; Baldwin, J. E.  Tetrahedron  2007, 63, 6331-6338.