Ph. D. THESIS 2009

2. Conclusions of the part A
Different saturated bicyclic compounds derived from tetramethyl 3,7dihydroxybicyclo[3.3.1]nona-2,6-diene-2,4,6,8-tetracarboxylate
1 have been
synthesized: diketone 2, spiro-monodioxane 3 and 4 and dioximes 5a and 5b.
The structural analysis has been performed by X-ray diffraction (four
single crystal structures), NMR at 300 MHz and 500 MHz, mass spectrometry,
FT-IR in solid state and in solution, and molecular modeling.
Synthesis of diketone 2 from precursor 1 was carried out following a novel
and uncatalysed straightforward strategy, classic and under microwave
irradiation, involving a one-step hydrolysis-decarboxylation route.
The structural analysis in solution and in solid state highlighted exclusively
the ketone form for compound 2 and the enol form, stabilized by intramolecular
H bonds, for the tetraester precursor 1.
Two possible structures of the enol form of compound 1, stabilized by
intramolecular H-bond between the enol ρ(C-O-H) fragment and ester groups
(carbonyl or methoxy fragment) have been modeled. The difference of energy
between these two forms, estimated from the theoretical work, is very low,
suggesting a fast inter-conversion between each other, .and the preference of
the H-bond interactions for the carbonyl fragment (confirmed by single crystal
X-ray diffraction).
The spiro-monodioxane 3 and 4 display a semi-flexible structure due to the
bicyclic skeleton rigidity and exhibit axial and elicoidal chirality, demonstrated
by the diastereotopicity of the 2'-C and 4'-C carbon atoms of the dioxane ring as
well as by the diastereotopicity of the Ha and Hb protons belonging to the
prochiral carbon atom of the bromomethyl substituent (compound 4).
The bicyclic dioxime 5 exhibits a particular case of axial chirality and the
corresponding stereoisomers syn and anti have been separated. The
thermodynamic and kinetic parameters of the syn-anti equilibrium were
determined by 1 H- NMR experiments.
Isomer syn (5a) is achiral (unlike) and isomer anti (5b) is chiral (like). The
chiral compound 5b was analyzed by chiral HPLC and its enantiomers were
discriminated.
The separated syn and anti isomers form stable H-bonds driven
supramolecular structures (cyclic dimer and trimer) by enantio- and
diastereospecific processes of self assembly based on four and six hydrogen
bonds, respectively. The structures are supported by single crystal X-ray
diffraction, FT-IR in solid state and in solution, NMR and molecular modeling.
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