Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations

Bao, Guanglin (2000) Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Kempane diterpenes such as 1 and 2, which are isolated from the defense secretions of nasute termite soldiers, are attractive and challenging targets for total synthesis. We have developed a highly stereoselective route, which is referred to as the Dithiane Route, to the kempane diterpene ring system that possesses all of the required stereogenic centers and sufficient functionality to allow for its conversion to the natural products. Our strategy took advantage of a highly regio- and endo-selective Diels-Alder reaction to construct the benzoindane ring system. 2-[1-[(tert-Butyldimethylsilyl)oxy]vinyl]-6,10-dithia-spiro[4,5]-dec-2-ene reacted with 2,6-dimethyl-1,4-benzoquinone to produce a cycloaddition adduct. The diene was prepared through a sequence that involved an alkylation of a dithiane compound with 2-methyl-2-(2-iodoethyl)-1,3-dioxolane, followed by an acid-catalyzed intramolecular aldol condensation. During the course of assembling the seven-membered ring cyclization precursor, a remarkably regioselective acetylide addition to a seemly more hindered carbonyl group was observed. In subsequent steps, a γ-hydroxyl group in an α,β-unsaturated ketone was cleaved by zinc reduction, followed by epimerization of a resulting decalin ring junction and double-bond isomerization catalyzed by ρ-toluene-sulfonic acid. In order to introduce the required double bond in the seven-membered ring at a later stage of the synthesis, a four-carbon side chain required for the target molecule was designed to be installed in two steps. Despite the failures of our "First Route" and "Diether Route", the Dithiane Route proved to be promising enough for construction of the kempane diterpene ring skeleton and elaboration to the natural products. -- To explore the possibility of introducing a methyl group at C-4 of kempane diterpenes, we investigated an electrophilic reaction of a silyl enol ether with 1,3-dithienium tetrafluoroborate and a cyclopropanation of a silyl enol ether. Model studies showed that indirect methylation of the TBS enol ether was successful, but that the subsequent acetylide addition step gave poor regio- and stereoselectivity. -- During the study of a cascade radical cyclization, a 5-exo-dig, 5-exo-trig tandem process and a 5-exo-dig, 6-exo-trig tandem process were achieved, although in low yield. It had been anticipated that this tandem radical cyclization strategy could provide an efficient approach to polycyclic compounds in high stereoselectivity.

Item Type: Thesis (Doctoral (PhD))
Item ID: 9334
Additional Information: Includes bibliographical references.
Department(s): Science, Faculty of > Chemistry
Date: 2000
Date Type: Submission
Library of Congress Subject Heading: Diterpenes--Synthesis; Ring formation (Chemistry)

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