My thesis was entitled Cross-Metathesis of Electron-Deficient Polyenes and Studies Toward the Total Synthesis of Arenolide, and it was completed under the advisement of Professor Tarek Sammakia at University of Colorado at Boulder. I graduated in 2012.
My initial thesis work centered on the selectivity of the cross-metathesis reaction between electron-deficient polyenes and a general terminal alkene by use of different metathesis catalysts. I examined this reaction using monoenes to tetraenes and determined that the reaction was most efficient when applied between a monoene or triene, providing the desired product in good to excellent yields. The selectivity is attributed to the reactivity of the terminal alkene of the triene which is furthest removed from the electron-withdrawing aldehyde or ester, rendering it the only alkene capable of reacting with the catalyst.
I also studied different approaches toward the total synthesis of arenolide, a 14-membered macrolide with unclear stereochemical assignment and bioactivity. My first approach utilized a 1,5-anti aldol reaction that was found to lack diastereoselectivity when applied to the total synthesis. The second-generation approach focused on alternative methods to produce the 1,5-anti relationship between the alcohols at C9 and C13 with the exo-methylene group at C11. All studies included the use of a key intramolecular vinylogous aldol macrocyclization developed in the Sammakia lab, which was shown to be effective on a model precursor very similar to that of arenolide.