A new annulation method and its application to terpenoid synthesis

• Main Author: Tse, Hoi Lun Allan
• Language: English
• Published: University of British Columbia 2010
• Subjects: Organic compounds > Synthesis; Terpenes
• Online Access: http://hdl.handle.net/2429/27553

The major theme of the work described in this thesis is concerned with the preparation of the β-trimethylstannyl enoates 53, 54 and 55, and their utilization in annulation processes. Treatment of the enol triflates 88, 91 and 92 with the cuprate reagent 56 produces compounds 53, 54 and 55, respectively, in good yields. Base promoted alkylation of the enoates 53 and 54 with 3-iodo-1-chloropropane provides the products 111 and 119. Under similar reaction conditions, 55 was alkylated with 1,4-dibromobutane and 1,5-dibromopentane to give 132 and 136. By employing standard reactions, 111, 119, 132 and 136 were converted into 113, 123, 134 and 141, respectively. Treatment of 113, 123, 134 and 141 with methyllithium in THF, in the presence of HMPA, led to the formation of the substituted bicycle[4.3.0]nonenes 114, 124 and 128, and the bicyclo[5.3.0]decene 142, respectively. The annulation method described above was applied successfully to the synthesis of the sesquiterpenoid (±)-chiloscyphone (151) and its isomer (±)-S-epi-chilos-cyphone (203). Thus, reaction of compounds 182 and 183, which were derived from 54 and the alkylating agent 178, with methyllithium in THF-HMPA provided the key bicyclic intermediates 184 and 190, respectively. These two compounds were subsequently transformed into 151 and 203. The sesquiterpenoid eremofukinone, whose structure was proposed as 204, was synthesized by exploiting the annulation method described earlier. Treatment of compound 228, which was produced from 54 and the dibromide 223, with methyllithium in 1,2-dimethoxyethane afforded the key intermediate 229 along with the diene 230. Suitable chemical manipulations converted 229 into 204. On comparing the ¹H nmr spectra of 204 and eremofukinone, substantial differences were noticed. Since compound 204 was constructed by an unambiguous route, it was concluded that the original structural proposal for eremofukinone is in error. [Formula Omitted] === Science, Faculty of === Chemistry, Department of === Graduate