Articles Manifestations of Bridgehead-Bridgehead Interactions in the Bicyclo[1.1.1]pentane Ring System William Adcock,* ,† Andrei V. Blokhin, ‡ Gordon M. Elsey, § Nicholas H. Head, † Alexander R. Krstic, † Michael D. Levin, ‡ Josef Michl,* ,‡ Jamie Munton, † Evgueni Pinkhassik, ‡ Marc Robert, | Jean-Michel Save ´ant,* ,| Alexander Shtarev, ‡ and Ivan Stibor ⊥ Department of Chemistry, The Flinders University of South Australia, Adelaide, Australia, 5001, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, Department of Chemical Sciences, Deakin University, Geelong, Victoria, Australia 3217, Laboratoire a’ Electrochimie Mole ´ culaire de L’Universite ´ Denis Diderot (Paris 7), 2 place Jussieu, 75251 Paris Cedex 05, France, and Institute of Chemical Technology, Prague, Czech Republic Received October 22, 1998 A series of 3-halo-substituted bicyclo[1.1.1]pentane-1-carboxylic acids 1 (Y ) COOH; X ) F, Cl, Br, I, and CF 3 ) as well as the parent compound 1 (Y ) COOH, X ) H) have been prepared, and a study of some of their properties have been made. It was found that their reactions with xenon difluoride cover a wide range of reactivities. On one hand, the fluoro acid 1 (Y ) COOH, X ) F) displayed no apparent reaction at all while, on the other, the bromo acid 1 (Y ) COOH, X ) Br) and parent compound 1 (Y ) COOH, X ) H) underwent ready reaction with complete disintegration of the ring system. A possible explanation is advanced based on polar kinetic and thermodynamic effects governing the lifetime of an intermediate acyloxy radical species. The relative ease of oxidation of the carboxylates 1 (Y ) COO - ;X ) H, F, Cl, Br, I, CF 3 , and COOCH 3 ), as mirrored by their peak oxidation potential values (E p ) determined by cyclic voltammetry, also covers a wide range. These data coupled with the dissociation constants (pK a ) of some of the acids 1 (Y ) COOH; X ) H, F, Cl, and CF 3 ) reflect significantly on the modes of transmission of electronic effects acting through the bicyclo[1.1.1]pentane ring system. Introduction Over the years the bridgehead positions of polycycloal- kanes have been shown to have considerable utility as probe sites for ascertaining structural and electronic factors underlying various physical and chemical phe- nomena. In the case of the bicyclo[1.1.1]pentane ring system (1) these positions are uniquely disposed being separated by only ca. 1.85 Å, 1 and hence cross-cage interactions are mandatory. Several striking manifesta- tions of strong bridgehead-bridgehead interactions in this system have now been recorded. 1-12 Theoretical considerations have largely centered on through-space interactions between the back- or rear-lobes of the bridgehead bond molecular orbitals which depend sen- sitively on the electronic characteristics of the substitu- ents or reaction site located at the bridgehead positions. In this paper we report the surprising course of the reactions between 3-halo and 3-trifluoromethyl-substi- tuted (X) bicyclo[1.1.1]pentane-1-carboxylic acids 1 (X ) F, Cl, Br, and CF 3; Y ) COOH) and xenon difluoride (XeF 2 ) which demonstrate further physical and chemical consequences of cross-cage interactions in this small bicyclic ring system. In addition, the dissociation con- stants of the carboxylic acids 1 (X ) H, F, Cl, and CF 3 ;Y ) COOH) have been determined and the electrochemical † The Flinders University. ‡ University of Colorado. § Deakin University. | L’Universite ´ Denis Diderot. ⊥ Institute of Chemical Technology. (1) Wiberg, K. B.; Hadad, C. M.; Sieber, S.; Schleyer, P.v. R. J. Am. Chem. Soc. 1992, 114, 5820 and references therein. (2) Wiberg, K. B.; Conner, D. S. J. Am. Chem. Soc. 1966, 88, 4437. (3) Barfield, M.; Della, E. W.; Pigou, P. E.; Walter, S. R. J. Am. Chem. Soc. 1982, 104, 3549. (4) (a) Kaszynski, P.; Michl, J. J. Org. Chem. 1988, 53, 4593. (b) Wiberg, K. B.; Waddell, S. T. J. Am. Chem. Soc. 1990, 112, 2194. (5) Adcock, W.; Krstic, A. R. Tetrahedron Lett. 1992, 33, 7397. (6) Toops, D. S.; Barbachyn, M. R. J. Org. Chem. 1993, 58, 6505. (7) (a) Maillard, B.; Walton, J. C. J. Chem. Soc., Chem. Commun. 1983, 900. (b) McKinley, A. J.; Ibrahim, P. N.; Balaji, V.; Michl, J. J. Am. Chem. Soc. 1992, 114, 10631. (8) Della, E. W.; Grob, C. A.; Taylor, D. K. J. Am. Chem. Soc. 1994, 116, 6159. (9) Wiberg, K. B.; McMurdie, N. J. Am. Chem. Soc. 1994, 116, 11990. (10) Adcock, W.; Clark, C. I.; Houmann, A.; Krstic, A. R.; Pinson, J.; Save ´ ant, J.-M.; Taylor, D. K.; Taylor, J. F. J. Am. Chem. Soc. 1994, 116, 4653. (11) Adcock, W.; Binmore, G. T.; Krstic, A. R.; Walton, J. C.; Wilkie, J. J. Am. Chem. Soc. 1995, 117, 2758. (12) Adcock, W.; Krstic, A. R. Magn. Reson. Chem. 1997, 35, 663. 2618 J. Org. Chem. 1999, 64, 2618-2625 10.1021/jo982124o CCC: $18.00 © 1999 American Chemical Society Published on Web 03/24/1999