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UBC Theses and Dissertations

Thermal rearrangement of 1,2-divinylcyclopropanes as applied to the total synthesis of (±)-β-himachalene and the synthesis of bicyclo [3.2.1.] octadienes Ruediger, Edward Herbert


The work described in this thesis involves two separate applications of the thermal rearrangement of 1,2-divinylcyclo-propane systems in organic synthesis. In the first case, the thermal rearrangement of the 3-(cyclopropyl)enone (100) to afford the seven-membered ring annelated product (101) comprised the key step in the total synthesis of (±)-β-himachalene (3). Compound (100) was readily prepared in six steps as follows. Treatment of acrolein with 2,2-dimethyl-1,3-propanediol in the presence of p-toluenesul-fonic acid afforded the acetal (117) which reacted with dibromo-carbene under phase transfer conditions to afford the crystalline dibromocyclopropane (116) . The latter material reacted stereoselectively with n-butyllithium and iodomethane at -95°C to give predominantly the cis-methylated cyclopropane (114). Acid hydrolysis of (114) afforded (E)-2-bromo-2-methylcyclo-propanecarboxaldehyde (113) which underwent a Wittig reaction with isopropylidenetriphenylphosphorane to yield the olefin (112). Successive treatment of (112) with t-butyllithium and phenylthiocopper led to the in situ formation of a lithium phenylthiocuprate reagent (111) which reacted with 3-iodo-2-cyclohexen-1-one to give the required β-(cyclopropyl)enone (100). Thermolysis (138°C) of (100) led to the exclusive formation of the bicyclic ketone (101). Methylation of ketone (101) followed by selective catalytic hydrogenation of the disubstituted double bond gave the ketone (127). Preparation of the enol phosphate (128) of the ketone (127) and reduction of the former with lithium in ethylamine completed the successful total synthesis of (±)-β -himachalene. The thermal rearrangements of a number of 6-alkenylbicyclo-[3.1.0]hex-2-enes (221) (R₁-R₄ = Me , H) to afford the corresponding bicyclo[3.2.1]octa-2,6-dienes (222) (R₁-R₄ = Me > H) are also described. The former were readily prepared in four steps from methyl acetoacetate. Thus, the alkylation of the dianion of methyl acetoacetate with (E)-5-bromo-1,3-pentadiene, (E)-5-bromo-2-methyl-1,3-pentadiene, (2E,4E)- and (2E,4Z)-1-bromo-2-methyl-2,4-hexadiene led to a series of β-keto esters. Diazo group transfer reaction of these β-keto esters afforded the corresponding a-diazo esters which underwent a copper-catalyzed intramolecular cyclization to give the appropriate 6-exo-(1-alkenyl)bicyclo[3.1.0]hexan-2-ones. Treatment of these ketones with lithium diisopropylamide followed by trapping of the resultant lithium enolates with tert-butyldimethylsilyl chloride led to the silyl enol ethers (221). Thermolysis (138°C or 165°C) of the latter led cleanly to the desired bicyclo-[3.2.1]octa-2,6-dienes (222). These rearranged silyl enol ethers were readily deprotected to give the corresponding β-keto esters. Similarly , 1-carbornethoxy-6-exo-vinylbicyclo [3 .1. 0] hex-3-en-2-one (237) rearranged thermally to afford 1-carbomethoxy-bicyclo[3.2.1]octa-2,6-dien-8-one (240). [diagrams not included]

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