Synthesis of isotopically labeled compounds and new transformations of functionalized sulfinate esters

Faragher, Robert James
Journal Title
Journal ISSN
Volume Title
University of Guelph

This thesis covers many different aspects of organic chemistry and is divided up into two main areas: incorporation of isotope labels and sulfinyl chemistry. There were two isotopically labeled substrates that were targeted and were prepared easily from literature procedures. Leflunomide is a recently approved drug that combats rheumatoid arthritis and was targeted with the incorporation of four 13C labels to determine the pharmacokinetics of the drug. A second substrate, perdeuterated 4-pentadecylpyridine ( 19) was prepared for investigating water incorporation into biomimetic bilayers. The first chapter concludes with new methodology developed for the preparation of determined length perdeuterated oligomeric (ethylene glycol) in high yields starting from immediate precursors through a Williamson reaction. After obtaining perdeuterated tetra(ethylene glycol) efficiently functionalized at both ends, it was successfully applied into the preparation of DPTL-'d'16 (22) and DPOL-'d'32 (23). The applications of DPTL and DPOL were for biomimetic bilayers precursors and to investigate the transportation of water through phospholipid membranes. Recent work with [alpha],[beta]-unsaturated sulfinate esters has only begun to explore the reactivity of this useful functional group. In the preparation of our [alpha],[beta]-unsaturated sulfinate esters 112 and 113, a byproduct of the oxidative fragmentation has been found. There have been some improvements developed for the preparation/isolation of 112 and 113. Lewis acid coordination studies have also been carried out with 112 and 113 to determine the coordination site for the Lewis acid on the dienophile. The Lewis acid studies provided corroborative evidence to explain the reactivity of our dienophiles. The versatility to prepare cycloadducts with 112 or 113 is explored further in the preparation of other cyclohexene derivatives with asymmetric and other symmetrical dienes in moderate to high yield, respectively. Recently prepared cycloadducts were reduced to the corresponding 1,3-mercapto carbinols and the reduction aided in the structural determination of the cycloadducts. Addition of Grignard reagents to various sulfinate ester cycloadducts has demonstrated an unusual phenomenon in that stereoconvergence occurs at the sulfinyl configuration. This phenomenon is explored in determining the generality of the reaction and breadth. As well, mechanistic considerations are also addressed.

isotope labels, sulfinate esters, substrate, synthesis