| dc.description.abstract | The present thesis initially describes a methodology for obtaining two series of
diastereoisomers of 1-aryl-4-hydroxy-2-thiaspiro[4,5]alkan-6-ones (5a-k and 6a-k), totaling 22
novel compounds by sulfa-Michael addition reaction. For this purpose, 1,4-dihydroxy-2,5-
dithiane was used under mild reaction conditions, such as ethanol as solvent and triethylamine
as a base, were used, and yields of 52 to 98% could be obtained. The influence of the size of
the spiro carbocyclic portion was evaluated, by using precursor (E)-2-arylidenecyclohexanones (3a-h) and (E)-2-arylidene-cyclopentanones (3i-k) as well as the impact of
different substituted aryl groups such as, phenyl, 4-methoxyphenyl, 4-nitrophenyl, 4-
fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 1-naphthyl, 4-(N,N)dimethylphenyl on the
stereoselectivity of the reactions. The resulting compounds were fully characterized from
spectroscopic analyses such as ¹H and ¹³C NMR, HSQC, HMBC, X-ray diffraction as well as
mass spectrometry. A preference for the formation of the diastereoisomer (1S,4S,5S) for the
cyclohexyl derivatives (a-h) and (1S,4R,5S) for the cyclopentyl derivatives (i-k) was observed.
As a derivation (application), fluorination reactions by nucleophilic substitution were also
carried out employing DAST. Modest yields on the order of 6 - 38% were obtained using
protocols established in the literature for fluorination of tetrahydrothiophenes. After ¹H, ¹³C and
¹9F NMR spectroscopic characterization, it was found that the reaction occurred in such a way
as to maintain the chiral configuration of the starting material, this feature being confirmed by
X-ray diffraction. Subsequently, this thesis studied the development of the synthesis and
derivatization reactions of a new model of trifluoromethyl substituted vinyl ketone, which was
obtained from the acetal acylation of (E)-2-benzylidene-cyclohexanone (2a) with
trifluoroacetic anhydride. Thus the structural characterization of (E)-1-(3-benzylidene-2-
methoxycyclohexenyl)-2,2,2-trifluoroethanone (10) was performed by ¹H and ¹³C NMR
techniques, as well as by single crystal X-ray diffraction. Additionally, the reactivity of the
three possible electrophilic centers of vinyl ketone 10 were assigned from the LUMO
coefficients, obtained by theoretical TD-DFT calculations. Experimental tests were carried out
from nucleophilic substitution and cyclo-condensation reactions, employing primary amines,
aryl and alkyl amines (04 compounds up to 95% yield); 1,2 dinucleophiles such as phenyl
hydrazine, semicarbazide and thiosemicarbazide (03 compounds, up to 68% yield); and 1,3
dinucleophiles like amidines, (03 compounds up to 68% yield). All these derivatives were
characterized by melting point, ¹H- and ¹³C NMR spectroscopy and HRMS analyses. | |
