Compounds containing the 2,3-dioxabicyclo[2.n.n] moiety, otherwise known as bicyclic endoperoxides, are a class of cyclic peroxides that are readily found in nature and can be utilized as important synthetic building blocks. The chemistry of endoperoxides has chiefly been concerned with the relative weakness of the peroxide bond, with comparatively little attention directed towards transformations of the alkene unit within these compounds. Therefore the focus of this thesis is on dihydroxylation of bicyclic endoperoxides and examination of their further utility. A broad range of 1,4-disubstituted-2,3-dioxabicyclo[2.2.2]oct-5-enes were synthesized featuring a variety of alkyl and aryl substituents. These compounds were subsequently dihydroxylated with osmium tetroxide to yield diols anti to the peroxide linkage, as single diastereomers, in excellent yields. Reduction of the peroxide bond afforded cyclohexane-1,2,3,4-tetraols of toxocarol relative stereochemistry in excellent yield; this configuration of hydroxyl groups is quite prevalent in nature. In order to demonstrate the synthetic scope of dihydroxylation of bicyclic endoperoxides followed by reduction of the peroxide linkage, tetraol formation from alkyl and aryl substituted diols was examined. It was confirmed that both alkyl and aryl substituents can be tolerated in the 1,4-positions. Dihydroxylation of endoperoxides containing H atoms at the 1,4-positions was also documented. The methodology of dihydroxylation followed by reduction of the peroxide linkage was employed to synthesize the reported natural product (1S,2R,3S,4R,5R)-2-methyl-5-(propan-2-yl)cyclohexane-1,2,3,4-tetrol in a short sequence from (R)-α-phellandrene. The 2,3-dioxabicyclo[2.2.2]octane-5,6-diols discussed above were also found to undergo an extremely clean rearrangement to yield 1,4-dicarbonyls and glycoaldehyde, a rearrangement not reported in the literature. The possible mechanism of this rearrangement was probed and is discussed in detail. The repercussions of diol orientation to product outcome were also investigated. Finally, the possibility of expanding the scope of synthetic application for this rearrangement, particularly the potential for synthesis of optically pure 1,4-dicarbonyls is discussed. Some preliminary results are reported. / Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 2009
| Identifer | oai:union.ndltd.org:ADTP/264728 |
| Date | January 2009 |
| Creators | Valente, Peter |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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