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New annulation methods employing bifunctional conjunctive reagents : total syntheses of (-)-homalomenols A and B

University of British Columbia

This thesis is divided into two parts. Part 1 describes the use of the bifunctional conjunctive reagent 13 in novel annulation sequences. As previously developed in our laboratories, compound 13 was converted into the key organocopper(I) reagent 15 which can be used as the synthetic equivalent of a 1-butene a²,d⁴-synthon 14 or a 1-butene d²,d⁴- synthon 21. The preparation of structurally complex tricycic ring systems of general structures 32 and 32a was accomplished via an annulation sequence involving: (a) the stereoselective conjugate addition of the organocopper(I) reagent 15 to bicyclic enones of general structure 19 to afford the vinylgermane intermediates 19a, (b) conversion of the vinylgermane adducts 19a into the corresponding keto vinyl iodides 19b, and (c) intramolecular Pd(0)-catalyzed coupling reactions of the vinyl iodides 19b to generate the unique tricydic keto alkenes 32 and 32a. The use of the organocopper(I) reagent 15 as the synthetic equivalent of the d²,d⁴- synthon 21 was employed in an annulation sequence designed to generate tricyclic compounds bearing an allylic, angular hydroxyl group (see general structure 33). The key step in this sequence involved the cyclization of the keto vinyl iodides 19b via a lithiumiodine exchange reaction and subsequent closure of the resultant vinyllithium species onto the carbonyl carbon. Part 2 of this thesis describes the first total syntheses of the sesquiterpenes (-)- homalomenol A (168b) and B (169b). The preparation of these products involved the conversion of the enantiomerically homogeneous allylic acetate 181b to the bicyclic enone 17Th via a known five-membered ring annulation sequence. The key steps were the stereoselective conjugate additions of the organocopper(I) reagents 178 and 179 to the bicyclic enone 177b. The resultant bicyclo[4.3.0]nonan-2-ones 175b and 176b were then readily converted to the products 168b and 169b, respectively, via two synthetic steps. [chemical compound diagrams]

Thesis/Dissertation

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2009-04-24

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http://hdl.handle.net/2429/7538

Chemistry

University of British Columbia

UBCV

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