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The use of camphor in sesquiterpenoid synthesis

University of British Columbia

This thesis, entitled "The use of camphor in sesquiter-penoid synthesis", consists of three chapters. Chapter One describes the conversion of (+)-8-bromocamphor (42) into a chiral dimethyl-acetal enolsilyl ether (105) that undergoes facile TiCl₄₋ promoted intramolecular cyclisation to provide tricyclic intermediates (195a,b), which after a series of functional group interconversions and the introduction of the gem-dimethyl group, leads to the first enantiospecific total synthesis of (+)-longiborneol (59) (ca. 13% in 21 steps from ( + )-camphor (26)). Oxidation of (+)-longiborneol (59) provides (+)-longicamphor (83), which was converted into (+)-longi-isoborneol (89) by reduction. Subsequent treatment with of (+)-longiisoborneol (89) with MsCl, 4-DMAP, and pyridine, reveals (+)-longifolene (61) (ca. 52% in 3 steps from (59)). Two other major attempts were also carried out prior to the successful synthesis of (59) and (61). Triene acetates (103a,b) were synthesised (ca. 8% in 10 steps from (+)-camphor (26)), but failed to undergo the intramolecular Diels-Alder reaction. In addition, (+)-campherenone (151) was also prepared (ca. 28% in 9 steps from (+)-camphor (26)), and both (151) and its derivatives (170), and (104) undergo SnCl₄-promoted intermolecular tertiary ∝-alkylation reaction to provide dimers (169a,b). Chapter Two describes two synthetic approaches to albene (221) which involves an intramolecular ene reaction, or an intramolecular free radical cyclisation reaction. A new enantiospecific synthesis route to (+)-β-santalene (259) (ca. 78% in 2 steps from (+)-campherenone (151)) is illustrated, however, (+)-β-santalene failed to undergo the intramolecular ene reaction to provide olefin (261). In addition, bromo-olefin (260) is also prepared (ca. 59% in 14 steps from (+)-camphor (26)), but cyclises in a 6-exo-trig mode in the intramolecular free radical cyclisation reaction to provide methyl ether (331). Chapter Three describes an evaluation of the potential use of (+)-5,6-dehydrocamphor (323) as a chiral synthon in the synthesis of the A,B ring system (cf. 329) of several classes of terpenoid. (+)-5,6-dehydrocamphor (323) was prepared from (-)-endo-3-bromocamphor (41) in two steps, and which is then converted to bicyclic enones (368a,b, 369a,b, 376a,b) by a sequence in which the key reaction was an anionic oxy-Cope rearrangement. Bicyclic enones (368a,b) were converted to tricyclic ketals (385a,b), but attempts to convert this compound to an angularly methylated intermediate (434) were unsuccessful. Furthermore, 1,5-dienols (409a,b), synthesised from (323) in ca. 50% yield, failed to undergo an anionic oxy-Cope rearrangement to provide bicyclic ketones (410a,b). Alternative ways of constructing an angular methyl group into the C(10) position in bicyclic enones (369a,b, or 376a,b) are currently being investigated in our laboratory. In addition, bicyclic ketones (373a,b) could serve as key intermediates in an enantiospecific synthesis of spirodysin (421), and indirectly to the synthesis of furodysin (422), and furodysinin (423). [Formula Omitted]

Text

2010-09-30

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http://hdl.handle.net/2429/28847

Chemistry

University of British Columbia

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