UCLA

In Chapter 1, rearrangements of 4-substituted bicyclo[2.2.2]oct-2-enyl-5-selenophenyl esters are explored. Reduction of the esters under radical-generating conditions initially generates a bicyclo[2.2.2]oct-5-en-2-yl radical which can rearrange to a bicyclo[3.2.1]oct-6-en-2-yl radical via a cyclopropylcarbinyl radical. Although the bicyclo[3.2.1]octene system exhibits greater strain than does the bicyclo[2.2.2]octene system, radical-stabilizing substituents can reverse this preference. The product ratios are influenced by the interplay of ring strain and radical stability. In addition, the rearranged products favored the equatorial over the axial isomers, which can be explained by torsional steering.

In Chapter 2, different approaches to the synthesis of the optically active bicyclo[2.2.2]octane-2,5-diones are presented. A stereoselective Diels-Alder cycloaddition was explored to construct the bicyclo[2.2.2]octane skeleton in an efficient manner. This approach was hindered by unexpected polymerization and lack of stereoselectivity. A different method of synthesizing the optically active bicyclo[2.2.2]octane-2,5-dione featuring a diastereoselective 1,4-addition is also presented.

In Chapter 3, progress toward the total synthesis of parthenolide is described. The synthetic route relies on ring-closing metathesis to close the 10-membered carbocycle of the natural product. The efforts leading up to and including the key ring-closing step are described. Specific attention is given to different methods for overcoming the difficulties associated with medium-sized ring formation.