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Bicyclo(3.2.1)octan-8-ones

University of British Columbia

The first part of this thesis is concerned with the development of a general synthetic approach to-the bicyclo(3.2.1)octane ring system. This work resulted in the successful synthesis of 1,5-dimethylbicyclo (3.2.1)octan-8-one(54) , 1,5-dimethylbicyclo (3.2.1)oct-6-en-8-one(55) and 1,5-dimethyl-6-isoproxybicyclo (3.2.1)oct-6-en-8-one(56). Alkylation of 2,6-dimethylcyclohexanone with allyl bromide afforded the olefinic ketones (78) and (79). Ozonolysis of the latter gave the keto aldehydes (80) and (81), which underwent a facile intramolecular aldol condensation to afford a mixture of the bicyclic alcohols (68) and (69). The mesylates (94_) and (9_5_) were obtained from the bicyclic alcohols (68J and (69_) . The keto iodide (70) , obtained by treating a mixture of the mesylates (94) and (95) with sodium iodide in refluxing acetone, was dehydrohalogenated to afford the desired bicyclic ketone (55). Hydrogenation of the latter over palladium afforded the desired bicyclic ketone (_54) . Oxidation of a mixture of the keto alcohols (68) and (69) with Collin's reagent afforded the diketone (71) which, under appropriate conditions, underwent O-alkylation to give the desired bicyclic enol ether (56) . In the second part of this thesis, the stereochemistry of nucleophilic addition to the 8-keto group present in the bicyclic ketones (54) , (55) and (56) was briefly investigated. The bicyclic ketones (54), (55) and (56) were reduced with lithium aluminium hydride to afford the bicyclic alcohols (112), (113) and (114) . Hydrogenation of the alcohol (113) yielded the alcohol (112). Hydrolysis of the enol ether (114) gave the ketol (116) . Hydrogenolysis of the dithioketal(117) of the keto alcohol (116) with Raney-nickel afforded alcohol (112). Thus, the bicyclic alcohols (112), (113) and (114) must have the same relative stereochemistry at C-8. The bicyclic ketones (5_4_) , (5_5) and (5_6_) were also treated with one equivalent of methylithium under identical conditions to form the corresponding tertiary alcohols (128), (129) and (130). These alcohols are also formed stereo-selectively and have the same relative stereochemistry as the corresponding secondary alcohols (112) , (113) and (114) .

Text

2010-01-20

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http://hdl.handle.net/2429/18706

Chemistry

University of British Columbia

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