Date on Master's Thesis/Doctoral Dissertation

5-2022

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemistry

Degree Program

Chemistry, PhD

Committee Chair

Hammond, Gerald

Committee Co-Chair (if applicable)

Nantz, Michael

Committee Member

Nantz, Michael

Committee Member

Grapperhaus, Craig

Committee Member

Valdes Jr., Roland

Author's Keywords

Halogenation; trifluoromethylation; trifluoromethylthiolation; dithiadication; Umemoto reagent; nitrile

Abstract

Organic halides are extensively utilized as synthetic intermediates in areas such as pharmaceuticals, agrochemicals, and material polymers. While many halogenating agents have been developed, they continue to have low efficiency or selectivity, are difficult to handle, and often have limited substrate scope. To address this issue, our laboratory has developed novel halogenating agents with improved stability and efficiency. In these studies, we demonstrated a novel application of halogenating reagent, HCl·DMPU, in the nitrile synthesis. We developed a novel method for C−SCF3/SeCF3 cross-coupling reactions using gold redox catalysis. We developed a novel trifluoromethylating agent in a cost-effective and highly efficient manner. We also attempted the development of dithiadication based electrophilic trifluoromethylating agents. With the objective of exploring other applications of HCl·DMPU beyond chlorination, we found a novel application of HCl·DMPU in one-pot conversion of aldehydes to nitriles. This method exhibited broad substrate scope with high yields for the aromatic, aliphatic, and α,β-unsaturated aldehydes incorporating various functional groups. We developed a novel application of halogenating agents like AgSCF3 and [(NMe4)(SeCF3)] in combination with commercially available gold catalyst [(MeDalphos)AuCl] for trifluoromethylthiolation (-SCF3) and trifluoromethylselenolation (-SeCF3) of the diverse array of aromatic, alkenyl and alkynyl halides and obtained the corresponding trifluoromethylthio and trifluoromethylseleno derivatives in good to excellent yields under mild reaction conditions . This protocol was successfully utilized in late-stage modification of various drug derivatives. In our quest of developing novel halogenating agents, we invented a newer version of Umemoto reagent II in one-pot synthesis from inexpensive starting material. This reagent is more powerful than Umemoto reagent II. and its applicability in the trifluoromethylation of various nucleophiles was demonstrated. In an attempt to explore the uncharted territory of trifluoromethylation, we designed and attempted to synthesize dithiadication electrophilic trifluoromethylating agents endowed with two transferable trifluoromethyl groups. However, our efforts to date have not produced satisfactory results.

Download

Share

COinS