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UBC Theses and Dissertations

Bifunctional organometallic reagents: preparation and use in annulation sequences Kaller, Alan Matthew


The use of bifunctional organometallic reagents (182, 35, and 271) to afford novel annulation products, such as the trans-fused bicyclo[3.3.0]octane (236) and bicyclo[4.3.0]nonane (83) systems and highly functionalized cyclopentene (273) systems, was investigated. The bifunctional reagent 132, was obtained in three steps from the bromo alcohol 134 via the alcohol 133 and the tosylate 158. The novel functionalized allylcopper(I) reagents, 162 and 182, were prepared from the corresponding allylstannanes 132 and 183 by treatment with methyllithium followed by CuBr∙Me₂S. These allylcopper(I) reagents were shown to add in a 1,4-fashion to a variety of α,β-unsaturated cyclic ketones (30) to provide ketones of general structures 191 and 192. A general annulation method for the preparation of trans-fused bicyclo[3.3.0]octane and bicyclo[4.3.0]nonane systems from a cyclopentanone system 61 was also developed. A palladium(O) catalyzed methoxycarbonylation of the alkenyl triflate 67, obtained from the keto ketal 61, provided the α,β-unsaturated ester 68, which was converted into the corresponding aldehyde 71. Conjugate addition of the allylcopper(I) reagent 182 or the lower order cyanocuprate 35, to the α,β-unsaturated aldehyde 71, were the key transformations to afford the aldehydes 239 and 80, respectively. Treatment of 239 or 80 with AModosuccinimide provided the alkenyl iodides 238 and 99 which underwent CrCl₂/NiCl₂-mediated cyclizations to provide the trans-fused bicyclo[3.3.0]octane and bicyclo[4.3.0]nonane systems, 237 and 102 & 103, respectively. These alcohols were converted into the corresponding ketones 236 and 83 in three additional steps. A copper(I) chloride-mediated intramolecular coupling reaction of alkenyltrimethylstannane moieties was used to provide highly substituted cyclopentene systems (273). Addition of 271, generated from 183 by treatment with methyllithium, to β-trimethylstannyl α,β-unsaturated aldehydes of general structure 275, followed by acetylation of the resultant alcohols provided 274. An intramolecular copper(I) chloride-mediated coupling of the alkenyltrimethylstannanes of general structure 274 gave the highly functionalized cyclopentenes of general structure 273. [Formula]

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