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UBC Theses and Dissertations

Studies on vinyl-alkyl based transition metal catalyzed coupling reactions and synthetic approach to the fusicoccane diterpenoids Fenster, Erik


Work relating to the transition metal catalyzed cross coupling of sp3 hybridized carbons to sp2 hybridized carbons is reported along with an asymmetric synthetic approach to the fusicoccane diterpenoids. A novel cross-coupling reaction between alkyl bromides (such as 2.40) with vinylzinc and vinylmagnesium reagents was developed. A catalytic system (5 mol % Pd(OAc)2, 5 mol % PCy3) and reaction conditions (NMP, 66 °C) were found which provided slightly over 50 % yield with a minimum amount of side product formation. The use of this reaction was explored in a tandem carboalumination/macrocyclization protocol. The formation of unsaturated macrocycles by way of intramolecular Negishi cross-coupling reaction was investigated. Neopentyl iodides were found to cross-couple with vinyl iodides in the intermolecular stereospecific formation of trisubstituted alkenes, although extending this to the complementary intramolecular reaction was challenging. Reaction conditions were found which allowed for the selective zinc activation of an alkyl iodide in the presence of a vinyl iodide contained within the substrate. The synthesis of the advanced intermediate towards fusicoccadiene, 4.2 was achieved in twenty-one steps (longest linear sequence) from the known (S)-(+)-4-(tertbutyldimethylsilyl) oxymethyl-Y-butyrolactone (4.15). Model studies revealed that fusicoccadiene may be obtained from 4.2 in additional four steps through the use of an acid catalyzed cyclodehydration reaction to form the C-ring. The formation of the 8-membered B-ring was achieved through the use of ring closing enyne metathesis. Other key features of the synthesis include the preparation of the functionalized cyclopentane A-ring through the use of a stereoselective Pauson-Khand [2+2+1] cycloaddition to establish the C-10 and C-14 stereocentres followed by the Norrish Type I reaction and an asymmetric cyclopropanation reaction to establish the remote C-7 stereocentre. Significantly, all stereocentres but one are established by stereochemical relay of the stereochemistry present in 4.15.

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