Graduation Year

2025

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Justin M. Lopchuk, Ph.D.

Co-Major Professor

Jianfeng Cai, Ph.D.

Committee Member

James Leahy, Ph.D.

Committee Member

Feng Cheng, Ph.D.

Keywords

Phosphonate, SuFEx, Asymmetric Synthesis, Bifunctionalization, Sulfoximine, Sulfonimidamide, Sulfinamide, Sulfonimidoyl Fluoride, Organolithium, Organomagnesium

Abstract

This dissertation mainly covers the development of synthetic methodologies related to several heteroatom functional groups, including phosphonates P(V), sulfoximines S(VI), sulfonimidamides S(VI), sulfonimidoyl fluorides S(VI), and sulfinamides S(IV). The interests in these functionalities are not only out of chemistry curiosity but also due to their pharmaceutical importance indicated by the existing drug molecules that contain these functional groups. The first chapter introduced the importance of phosphonates in biochemistry and organic synthesis, also provided some essential background of our synthetic efforts. The second chapter described the phosphonate synthesis from commercially available starting materials, with the purpose to obtain heterocyclic phosphonates in a modular fashion. The method development and rationale were based on our previous S(VI) chemistry knowledge. The third chapter introduced the importance of S(VI) and S(IV) chemistry and O to N replacement on sulfur functional groups in pharmaceutical discoveries, as well as existing synthetic methods. The chapter also provided some knowledge of chemical species related to our synthetic efforts. The fourth chapter described the development of a platform for the asymmetric synthesis of sulfoximines, sulfonimidamides and sulfonimidoyl fluorides from a readily available enantiopure reagent. The reagent development, synthetic applications, substrate scope and explorations of each stage were explained in details.

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