Development of a new methodology for the synthesis of haloconduritols and gold catalyzed alkyne cyclizations of n-propargyl substituted indole derivatives /

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2015
Kaya, Serdal
Because of the biological properties and being useful intermediates, haloconduritols became synthetically important molecules. During the last decades, some methodologies have been developed for the construction of haloconduritol derivatives. Our synthetic strategy was based on stereospecific hydroxylation of one of the double bonds of commercially available cyclopentadiene. After protection of the hydroxyl groups as a ketal, the remaining double bond was submitted to the dibromocarbene addition reaction. Silver-promoted ring opening reaction of the tricyclic compound resulted in the formation of a six-membered ring with a double bond having a bromine atom. Removal of the ketal group under the acidic conditions gave bromocyclo-hexenetriols In the second part of the thesis, the main interest was concentrated on the synthesis of nitrogen containing heterocycles. For this purpose, starting from N-propargyl-2-indole carbaldehyde or N-propargyl-2-indole carboxylic acid, the synthesis of the nitrogen containing heterocycles, such as pyrazino-indole-N-oxide, pyrazolo-pyrazino-indole, diazepino-indole and pyrazolo-diazepino-indole derivatives, were planned. Ring cyclization was carried out in the presence of Au(III) salt and NaH. Cyclization of oxime derivative derived from N-propargyl-indole aldehyde gave the corresponding pyrazine oxides. In case of substituted alkynes, an oxime-oxime rearrangement was observed which was unprecedented in the literature. Gold-catalyzed cyclization of N-propargyl indoles having a pyrazole ring attached to the C-2 carbon atom underwent 6-exo-dig and 7-endo-dig cyclization reactions depending on the nature of the substituents attached to the terminal alkyne group. However, NaH-supported cyclization resulted in the formation of six-membered rings.
Citation Formats
S. Kaya, “Development of a new methodology for the synthesis of haloconduritols and gold catalyzed alkyne cyclizations of n-propargyl substituted indole derivatives /,” Ph.D. - Doctoral Program, Middle East Technical University, 2015.