Date

2017

Document Type

Dissertation

Degree

Doctor of Philosophy

Department

Chemistry

First Adviser

Vicic, David A.

Other advisers/committee members

Flowers, II, Robert A.; Ferguson, Gregory S.; Nataro, Chip

Abstract

Fluorine-containing molecules have become increasingly more prevalent in life sciences, agricultural, and materials fields. Difluoromethylene and trifluoromethyl moieties can modify the electronic properties as well as the hydrophobicities of the parent molecules. These groups also are much more resistant to degradation and metabolic decomposition pathways relative to their non-fluorinated counterparts, a feature that is especially important for medicinal applications. Herein, I report the preparation of novel dinuclear zinc reagents from commercially available α,ω-diiodoperfluoroalkanes and dibromoperfluoroalkanes for the preparation of both fluoroalkyl ring systems and linear fluoroalkyl linked arenes under relatively mild conditions. Additionally, the dizinc reagents are more stable and more versatile than analogous α,ω-dinucleophiles previously developed. The formation of varying (CF2) linker lengths can be achieved with only minor modifications to the conditions. I also detail my first efforts to develop a catalytic method for polydifluoromethylenation of both aryl iodides and aryl diiodides. In addition to the protocol described above, I describe a new route to prepare fluoroalkylated chains that are unsymmetrically disubstituted with aryl end groups. My approach involved the use of a novel α-bromo-ω-silyl fluoroalkane. Using the appropriate silver salt and ligand, the isolable silver reagent, [(phen)Ag(CF2)nBr], could be prepared in good yields. This reagent undergoes cross-coupling with aryl iodides in the presence of a copper catalyst to form the targeted arylated fluoroalkyl bromide building blocks. Lastly, copper complexes containing fluoroalkyl moieties have been employed in a myriad of protocols, yet I am not aware of any studies comparing their efficacy under similar conditions for fluoroalkylations. By studying well-known metal catalyzed trifluoromethylations of aryl halides, I benchmarked several copper trifluoromethyl reagents. I believe the findings reported should help others better understand these reactions.

Available for download on Friday, June 01, 2018

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