Synthesis of the kempane diterpene ring system, and regio- and stereoselectivity in the reductions of cyclic enediones

Liu, Chunjian (1998) Synthesis of the kempane diterpene ring system, and regio- and stereoselectivity in the reductions of cyclic enediones. Doctoral (PhD) thesis, Memorial University of Newfoundland.

[img] [English] PDF - Accepted Version
Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.

Download (8Mb)


Kempane diterpenes such as 1 and 2, which are a class of compact tetracyclic compounds isolated from the defense secretions of nasute soldier termites, have been challenging synthetic targets. We have achieved a highly stereoselective synthesis of the kempane diterpene ring system that possesses all the required stereogenic centers and sufficient functionality to allow elaboration to 1 and 2. A key step of our synthesis of the ring system is the highly regia- and facially-selective Diels-Alder cycloaddition of cis-5-(I-((tert-butyldimethylsilyl)oxy)vinyl)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one (78) and 2,6-dimethyl-1,4-benzoquinone (13) to establish the benzoindane ring system 79. The diene 78 was prepared through a sequence that contained a regiospecific [2 + 2] cycloaddition of 1-methyl-1 ,3-cyclohexadiene (38) with dichloroketene, generated in situ from dichloroacetyl chloride and triethylamine. Though attempts to cyclize the seven-membered ring in hemi-acetal 72 by aldol reaction were unsuccessful due to the difficulty in opening the five-membered hemi-acetal ring, the seven-membered ring was constructed by a regiospecific Dieckmann condensation in ethyl (1α,2β,4α,4aβ,6β,6aα,7aβ,10aβ,10bα,10cα)-2,3,4,4a,5,6,6a,7,7a,10,10a,10b,10c-tridecahydro-4-hydroxy-6-(2-methoxyethoxy)methoxy-2,10c-dimethyl-9-oxo-1Hbenz[6,7]indeno-[2,1-b]furan-l-methylcarboxylate (131). The transformation of the benzoindane ring system 79 to carboxylate 131 involved a remarkably regio- and stereoselective addition of an acetylide to the apparently more hindered carbonyl in 79, a reductive cleavage of a γ-hydroxy group in an α,β-enone system, and a one-pot acid-promoted epimerization and double-bond isomerization. -- To explore the possibility of modifying our synthesis of the kempane diterpene ring system to an asymmetric approach, we investigated the asymmetric [2 + 2] cycloadditions of enantiopure, L-menthoxy- and 1,2:5 ,6-di-O-isopropyllidene-a-D-glucofuranoxy-substituted ketenes 174 and 185 with cyclopentadiene (175). -- In the course of the synthetic study towards kempane diterpenes, an exiremely regia- and stereoselective reduction of the seemingly more hindered carbonyl in enedione 56 with lithium tri-tert-butoxyaluminohydride or sodium borohydride was observed. Systematic study proved this observation to be general with non-bridged cyclic enediones. Both the regio- and stereoselectivities are due to a preference for axial attack by the reducing reagents. Among possible axial additions to the two carbonyls, only one approach is sterically allowed. It was also found that the combination of sodium borohydride and cerium trichloride, the Luche reagent, was a useful alternative reducing reagent. It either improved or completely reversed the regioselectivity.

Item Type: Thesis (Doctoral (PhD))
Item ID: 10906
Additional Information: Includes bibliographical references.
Department(s): Science, Faculty of > Chemistry
Date: 1998
Date Type: Submission
Library of Congress Subject Heading: Carbonyl compounds; Diterpenes--Synthesis.

Actions (login required)

View Item View Item


Downloads per month over the past year

View more statistics