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UBC Theses and Dissertations

Methylenecyclohexane annulations : total syntheses of axane-type sesquiterpenoids Yeung, Bik Wah Anissa


This thesis describes the preparation of 5-chloro-2-trimethyl-stannyl-1-pentene (111) and its conversion into 5-chloro-2-lithio-1-pentene (112). The latter reagent, which reacts smoothly with cyclohex-anone at -78°C to give 5-chloro-2-(1-hydroxycyclohexyl)-1-pentene (132), was found to be thermally unstable at temperatures higher than -63°C. Reagent (112) was transformed into the Grignard reagent (144) and the organocopper-phosphine complex reagent (145). Conjugate addition of reagents (144) and/or (145) to cyclic enones under appropriate conditions followed by cyclization of the resultant products, effected useful methylenecyclohexane annulation sequences [(104) → (116)]. This methylenecyclohexane annulation method served as one of the two key steps in the syntheses of (±)-axamide-1 (174), (±)-axiso-nitrile-1 (173), and the corresponding C-10 epimers. Thus, copper(I)-catalyzed addition of the Grignard reagent (144) to 2-methyl-2-cyclo-penten-1-one (152), followed by cyclization of the resultant chloro ketone (159), gave the annulation product (170), which was converted into the enone (203). The other key step in the projected synthesis, which involved TiC1₄-catalyzed conjugate addition of the bis(trimethyl-silyl) ketene acetal (226) to the enone (203), provided a mixture of the keto acids (222) and (223). With appropriate functional group manipulations, (222) was converted into (±)-axamide-1 (174) and (±)-axisonitrile (173), while (223) was converted into (±)-10-epi-axamide-1 (224) and (±)-10-epi-axisonitrile-1 (225). [Formula Omitted]

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