ORGANIC
LETTERS
2006
Vol. 8, No. 4
749-752
cis-endo-Bicyclo[1.1.1]pentane-1,2,3,4-
tetracarboxylic Acid and Its Derivatives
Ctibor Mazal,*,‡ Ondrˇej Skarka,‡ Jirˇ´ı Kaleta,‡ and Josef Michl†
ˇ
Department of Organic Chemistry, Masaryk UniVersity, Kotla´rˇska´ 2, 611 37 Brno,
Czech Republic, and Department of Chemistry and Biochemistry, UniVersity of
Colorado, Boulder, Colorado 80309-0215
Received December 14, 2005
ABSTRACT
We report the synthesis of cis-endo-bicyclo[1.1.1]pentane-1,2,3,4-tetracarboxylic acid and several of its derivatives with differentiated bridgehead
and bridge positions, starting with tetracyclo[3.2.0.01,6.02,6]heptane.
We are interested in the possibility that close spatial
proximity of multiple functional groups crowded on a small
cage, such as bicyclo[1.1.1]pentane, might lead to unusual
properties as a result of their mutual interactions. In addition
to offering interesting substrates for reactivity studies, highly
functionalized bicyclo[1.1.1]pentanes might also provide
future access to bridge-functionalized [1.1.1]propellanes and
thus to laterally substituted [n]staffane molecular rods.1
Although numerous bicyclo[1.1.1]pentanes substituted
only in the bridgehead positions are known,2 those also
functionalized on the bridges are extremely rare. 1,3-
Disubstituted 2,2-dichloro and 2,2-dibromo derivatives were
prepared by reaction of bicyclo[1.1.0]butane derivatives with
dichloro3-6 and dibromo carbenes, respectively. Such tetra-
substituted bicyclo[1.1.1]pentanes were also prepared by
direct chlorination of bicyclo[1.1.1]pentane-1,3-dicarboxylic
acid, its dichloride,7 and 1,3-dibromobicyclo[1.1.1]pentane.8
Interestingly, 2-monochloro derivatives did not accumulate
and had to be obtained by subsequent partial dehalogenation.
Direct fluorination of the 1,3-dicarboxylic acid provided
almost all of the possible fluorinated diacids which were
separated and used for an investigation of long-range NMR
coupling constants.9,10 Some 2,2-difluoro derivatives have
been patented as structural units for liquid crystals.11 Carbon-
linked bridge substitution is only represented by 2,4-ethano12
and 2,4-propano13-16 bridged derivatives (tricyclo[3.2.0.02,6]-
heptanes and tricyclo[4.2.0.02,7]octanes, respectively) and by
poly[1.1.1]propellanes, whose bicyclo[1.1.1]pentane cages
carried an alkyl chain,17 including one with a remote hydroxyl
function18 used to anchor a dendritic fragment.19
(8) Hamrock, S. J.; Michl, J. J. Org. Chem. 1992, 57, 5027.
(9) Levin, M. D.; Hamrock, S. J.; Kaszynski, P.; Shtarev, A. B.; Levina,
G. A.; Noll, B. C.; Ashley, M. E.; Newmark, R.; Moore, G. G. I.; Michl,
J. J. Am. Chem. Soc. 1997, 119, 12750.
(10) Shtarev, A. B.; Pinkhassik, E.; Levin, M. D.; Stibor, I.; Michl, J. J.
Am. Chem. Soc. 2001, 123, 3484.
(11) Yano, H.; Takeuchi, H. Jpn. Kokai Tokkyo Koho 1998 JP 10168453
A2 19980623 Heisei. CAN 129:142670.
(12) Mazal, C.; Paraskos, A. J.; Michl, J. J. Org. Chem. 1998, 63, 2116.
(13) Stroeter, T.; Szeimies, G. J. Am. Chem. Soc. 1999, 121, 7476.
(14) Bunz, U.; Szeimies, G. Tetrahedron Lett. 1990, 31, 651.
(15) Schlueter, A. D.; Wegner, G.; Feast, W. J. Angew. Chem. 1988,
100, 283.
(16) Belzner, J.; Szeimies, G. Tetrahedron Lett. 1987, 28, 3099.
(17) Bothe, H.; Schlueter, A. D. AdV. Mater. 1991, 3, 440.
(18) (a) Freudenberger, R.; Lamer, W.; Schlueter, A. D. J. Org. Chem.
1993, 58, 6497-6498. (b) Lassale, I.; Schmidt, M.; Schlueter, A. D. Acta
Polymer 1994, 45, 389.
‡ Masaryk University.
† University of Colorado.
(1) Schwab, P. F. H.; Levin, M. D.; Michl, J. Chem. ReV. 1999, 99, 1863.
(2) Levin, M. D.; Kaszynski, P.; Michl, J. Chem. ReV. 2000, 100, 169.
(3) Applequist, D. E.; Wheeler, J. W. Tetrahedron Lett. 1977, 3411.
(4) Applequist, D. E.; Renken, T. L.; Wheeler, J. W. J. Org. Chem. 1982,
47, 4985.
(5) Hall, H. K., Jr.; Smith, C. D.; Blanchard, E. P., Jr.; Cherkofsky, S.
C.; Sieja, J. B. J. Am. Chem. Soc. 1971, 93, 121.
(6) Potekhin, K. A.; Maleev, A. V.; Struchkov, Yu. T.; Surmina, L. S.;
Koz’min, A. S.; Zefirov, N. S. Dokl. Akad. Nauk SSSR Ser. Khim. 1988,
298, 123.
(7) Robinson, R. E.; Michl, J. J. Org. Chem. 1989, 54, 2051.
10.1021/ol053039n CCC: $33.50
© 2006 American Chemical Society
Published on Web 01/20/2006