Synthetic
and theoretical studies on highly pyramidalized alkenes
Research Interests
The polycyclic structure of tricyclo[3.3.0.03,7]octane (bisnoradamantane) is very fascinating for both synthetically and theoretically oriented organic chemists due to their intriguing physical properties and their interesting reactivity. During more than twenty years our group has been engaged in a project aimed to understand the structure and the reactivity of bisnoradamantane derivatives. We have developed two general entries to this strained carbocyclic skeleton and we have synthetized and dimerized several highly pyramidalized alkenes contained into the bisnoradamantane system in order to build more complex polycyclic structures.
Two general entries to the bisnoradamantane skeleton:
We have developed two general entries to the bisnoradamantane skeleton. Our first approach involves the iodine induced oxidation of bis-enolates of bicyclic esters of general structure I. Several diesters of general structure II have been synthetized in medium to good yields. A second approach involves the pinacol-type coupling of diketones of general structure III to compounds IV by using TiCl4 / Zn. Several pinacols have been synthetized in excellent yields.
Scheme 1
Synthesis, chemical trapping and dimerization of several highly pyramidalized alkenes:
The ideal geometry for a double bond has the olefinic carbon atoms and the four substituents of the double bond in the same plane. However, when a double bond is located at the bridgehead position in a polycyclic structure the two planes formed by each of the olefinic carbons and the substituents attached to them are not coplanar. This phenomenon is called pyramidalization and this kind of double bond is pyramidalized.
Figure 1
Thus, while alkenes
react usually with electrophiles, pyramidalized alkenes are highly reactive
towards nucleophiles and dienes, while in the absence of such reagents
they usually dimerize to give cyclobutanic dimers. These cyclobutanic
derivatives can undergo a [2+2] retrocycloaddition to give isomeric
dienes (scheme 2). We have published the syntheses, chemical trapping
and dimerization of several highly pyramidalized alkenes. Moreover,
we have developed a new methodology in order to generate highly pyramidalized
alkenes in excellent yields and we have carried out the first cross-coupling
reaction of two highly pyramidalized alkene, leading to functionalized
tetrasecododecahedradienes (scheme 3).
Scheme 3
Recently, we have generated pyramidalized alkene 13. The dimerization of 13 did not lead to a cyclobutane derivative but to an orthogonally fused dimer, 15. The unusual formation of 15 can be explained through a radical cascade process (scheme 4).
Scheme 4
Current projects:
a) Although much work has been done on pyramidalized alkenes, much of the efforts have mainly been of interest to physical organic chemist, owing to the lack of synthetic utility of the dimers. This is because most of the studied compounds were hydrocarbons without functional groups. As a part of our ongoing interest in pyramidalized alkenes, currently we want to synthesize a series of precursors of pyramidalized alkenes bearing functional groups compatible with the conditions needed to generate them. Functional group manipulations on the cyclobutanic dimers may lead to more complex polycyclic products. We also intend to carry out theoretical (ab initio and molecular mechanics calculations) and experimental (photoelectron spectroscopy, differential scanning calorimetry, etc) studies on the pyramidalized alkenes and the polycyclic compounds derived from them. The study of the - interactions between double bonds closed to the space, the study of transannular reactions and the possibility of complexing some of these compounds with metals would be of great interest.
b)
Moreover, although our group has a broad experience on the synthesis
of polycyclic cage compounds such as bisnoradamantane, homoadamantane,
noradamantane and adamantane derivatives, to date, we have not carried
out studies directed towards the synthesis of biologically active bisnoradamantane,
noradamantane or homoadamantane derivatives. Currently, we are working
in the synthesis of aminopolyciclic cage compounds as potentially pharmacologically
active compounds. Our first, very interesting, results will be reported
soon.
Recent papers
1.-
P. Camps, X. Pujol, R. A. Rossi, S. Vázquez. Synthesis of Several
8-Halopentacyclo [6.4.0.02,10.03,7.04,9]dodecane Derivatives, Synthesis,
1999, 854-858.PDF
2.- P. Camps, A. Lukach, X. Pujol, S. Vázquez, Hunsdiecker-Type
Bromodecarboxylation of Carboxylic Acids with Iodosobenzene Diacetate-Bromine,
Tetrahedron, 2000, 56, 2703-2707.PDF
3.- P. Camps, X. Pujol, S. Vázquez. Cross-Coupling of Highly
Pyramidalized Alkenes: A Straightforward Access to Functionalized Tetrasecododecahedradienes.
Org. Lett., 2000, 2, 4225-4228.PDF
4.- P. Camps, A. E. Lukach, S. Vázquez, Formation and cleavage
of bisnoradamantane derivatives through SmI2 reductions, Tetrahedron,
2001, 57, 2419-2425.PDF
5.- P. Camps, A. E. Lukach, R. A. Rossi, Synthesis of several halobisnoradamantane
derivatives and their reactivity through the SRN1 mechanism, J. Org.
Chem., 2001, 66, 5366-5373.PDF
6.- P. Camps, X. Pujol, S. Vázquez, M. A. Pericàs, C.
Puigjaner, L. Solà, Cross-Coupling of a functionalized highly
pyramidalized Alkene: DSC and NMR study of the [2+2] retrocycloaddition
of cyclobutane cross products, hyperstability and pyramidalization of
the formed dienes. Tetrahedron, 2001, 57, 8511-8520.PDF
7.- P. Camps, X. Pujol, S. Vázquez, Synthesis and reactivity
of a new functionalized and highly pyramidalized alkene containing the
bisnoradamantane skeleton and its diene dimer. Tetrahedron 2002,
58, 10081-10086.PDF
8.- S. Vázquez, GIAO-DFT study of 13C NMR chemical shifts of
highly pyramidalized alkenes. J. Chem. Soc., Perkin Trans. 2 2002,
2100-2103.PDF
9.- P. Camps, J. A. Fernández, S. Vázquez, M. Font-Bardia,
X. Solans, Generation., trapping, and dimerization of pentacyclo[6.4.0.02,10.03,7.04,9]dodeca-5,8,11-triene:
An Uncatalyzed Thermal [2+2+2+2] cycloaddition, Angewandte Chemie,
International Edition, 2003, 42, 4049-4051.PDF
10.- C. Ayats, P. Camps, M. D. Duque, M. Font-Bardia, M. R. Muñoz,
X. Solans, S. Vázquez, Alternative syntheses of the new D2d symmetric
tetramethyl tricyclo[3.3.0.03,7]octane-1,3,5,7-tetracarboxylate, Journal
of Organic Chemistry, 2003, 68, 8715-8718. PDF
11.-P.
Camps, J.A. Fernández, M. Font-Bardia, X. Solans, S. Vázquez,
Diels–Alder reactions of highly pyramidalized
tricyclo[3.3.0.03,7]oct-1(5)-ene derivatives: further chemistry of pentacyclo[6.4.0.02,10.03,7.04,9]dodeca-5,8,11-triene,
Tetrahedron, 2005, 61, 3593-3603. PDF
12.- S. Vázquez, P. Camps, Chemistry of pyramidalized alkenes, Tetrahedron, 2005, 61, 5147-5298. PDF
13.
P. Camps, M.R. Muñoz, S. Vázquez, Generation and Reactions
of Two New FunctionalizedTricyclo[3.3.0.03,7]oct-1(5)-ene Derivatives,
Journal of Organic Chemistry, 2005, 70, 1945-1948.
PDF
Current and past collaborations
Prof. Dr. Rolf Gleiter, Organisch-Chemisches Institut
der Universität Heidelberg (Germany).
Prof. Dr. Miguel A. Pericàs & Dr. Lluís Solà,
Servei de Calorimetria de Reacció, Parc Científic de Barcelona
(Barcelona).
Prof. Dr. F. Javier Luque, Departament de Físico-Química,
Universitat de Barcelona (Spain).
Prof. Dr. Roberto A. Rossi, Universidad de Córdoba (Argentina).
| Dr. Pelayo Camps García
camps@ub.edu |
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