Darstellung von perfluoralkyl- und perfluoraryl-substituierten Heterocyclen ausgehend von Donor-Acceptor-Cyclopropanen

Abstract

Die vorliegende Arbeit beschreibt die Darstellung von perfluoralkyl- und perfluoraryl-substituierten Heterocyclen durch Reaktionen von entsprechend substituierten 2-Siloxycyclopropancarbonsäureestern. Ausgehend von perfluorsubstituierten Ketonen wurden fluorierte Silylenolether dargestellt, welche in Übergangsmetall-katalysierten Cyclopropanierungen mit α-Diazoestern umgesetzt wurden. Die erhaltenen Donor-Acceptor-Cyclopropane dienten in Folgereaktionen als Äquivalente von 1,4-Dicarbonylverbindungen. Diese wurden einerseits isoliert oder in situ freigesetzt und durch Addition von Nukleophilen zu Lactonen und Pyridazinonen mit potentieller biologischer Aktivität umgesetzt. Ein alternativer Weg führte über die Deprotonierung und Addition der Siloxycyclopropane an Heterocumulene zu fluorierten Thiophen- und Pyrrolderivaten, die zu Heterocyclen mit potentieller Anwendung als funktionale Materialien umgesetzt wurden. Desweiteren wurde ein Cyclopropanderivat in Multikomponentenreaktionen eingesetzt, woraus fluorierte Aminosäurederivate erhalten wurden, die Anwendung als Peptidmimetika finden könnten.

Aim of the dissertation was to find access to perfluoroalkyl- and perfluoroaryl-substituted 2-siloxycyclopropanecarboxylates starting from commercially available or easily accessible fluorinated materials. The cyclopropane derivatives should be used as C3 building blocks for the rapid construction of heterocyclic compounds with potential biological activity. Inspired by the great interest that organofluorine compounds in general and fluorinated heterocyclic compounds in detail received in the last decades as well as the synthetic potential of donor-acceptor-cyclopropanes as building blocks in organic synthesis, perfluoroalkyl- and perfluoroaryl-substituted 2-siloxycyclopropanes were prepared by cyclopropanation of perfluoroalkyl- and perfluoroaryl-substituted silyl enol ethers with diazo esters. The equivalence of the cyclopropane derivatives with 1,4-dicarbonyl compounds was shown by fluoride-promoted desilylation and ring opening yielding γ-oxo esters in excellent yields. Furthermore, the siloxycyclopropanes were used as masked carbonyl compounds in one pot transformations which afforded fluorinated γ-hydroxy esters, γ-lactones or pyridazinone derivatives with potential biological activity in good overall yields. The cyclopropanes were also deprotonated and addition of the produced ester enolates to alkyl halides furnished the alkylated derivatives in good yields and excellent diastereoselectivities, enhancing the flexibility of the synthetic route. This concept was extended by the addition of these ester enolates to heterocumulenes, by which ring-expanded intermediates and ultimately perfluoroalkyl-substituted thiophenes and pyrroles were obtained. A fluorinated siloxycyclopropane was also applied in the UGI-multicomponent reaction affording novel fluorinated δ-amino acids, amino acid derivatives and pyrrolidinones that could possibly mimic peptides. Finally, ethyl diazo- trifluoropyruvate was employed as a component in 1,3-dipolar cycloaddition reactions with alkynes yielding polyfluorinated pyrazoles. The rate of the reactions, the regioselectivity of addition and the VAN ALPHEN-HÜTTEL rearrangement of the obtained products were studied.