Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Since Friedrich Wöhler’s synthesis of urea in 1828, the techniques of organic synthesis have developed and advanced greatly. This advancement has facilitated the discovery of new organic synthetic methods, and enabled access to a more expansive chemical space. The purpose of this dissertation is to present the development of new organic synthetic reactions that were uncovered through previous discoveries. Additionally, the main theme of this work relies on exploiting the versatility of triphosgene in organic synthesis. To this end, the developed chemistries rely on the ability of triphosgene to serve as an activating agent, and a chloride source.

Chapter 1 highlights selected advances in triphosgene-enabled organic synthetic reactions in the last decade. This briefly showcased the utility of triphosgene in the synthesis of organohalides and heterocycles, among others. Additionally, the application of triphosgene in polymer synthesis, as well as in techniques, such as flow chemistry and solid-phase synthesis is illustrated.

Chapter 2 is centered around our newly developed triphosgene-DMAP protocol for the dehydration of tertiary alcohols. The chapter begins with a quick survey of previously reported approaches, followed by our newly developed method. This study showcased the utility of triphosgene-DMAP mixture in the dehydration of various acyclic and cyclic tertiary alcohols. In addition, the developed protocol was ultimately applied to the late-stage dehydration of the methylated derivative of commercially available allergy medicine, singulair®.

Finally, Chapter 3 briefly introduces the pyranoside core and provides a review of the various ways for the synthesis of these cores. This chapter also illustrates our attempt at developing a method for the diastereoselective synthesis of chlorinated tetrahydropyranosides from d,e- Epoxyketones. The developed protocol involves using a mixture of triphosgene and pyridinium ion to circumvent the innate reactivity of d,e-Epoxyketones towards bicyclic ketal formation.

Thereby, harnessing the epoxyketones towards pyranoside synthesis. This developed procedure was subsequently applied to the synthesis of various aliphatic, aromatic, and heterocyclic bearing pyranosides. The adaptability of the developed method for the synthesis of tetrahydropyran was demonstrated by quenching with a hydride source. Ultimately through this study, we were able to uncover the unprecedented chemoselective activation of an epoxyketone with triphosgene, as well as discover a novel counterion-based selectivity during the ionization of epoxyketones.

Committee Chair

Kartika, Rendy G.

DOI

10.31390/gradschool_dissertations.5838

Available for download on Thursday, April 24, 2025

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