Date of Graduation

7-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

McIntosh, Matthias C.

Committee Member

Allison, Neil T.

Second Committee Member

Thallapuranam, Suresh

Third Committee Member

Zheng, Nan

Keywords

2-ketoazoles; Azoles; Breslow intermediate; Claisen Rearrangement; Tertiary alcohols; Thiamine

Abstract

This work describes efforts targeted at the development of novel reactivity modes for the Breslow intermediate, which was proposed by Breslow to explain the mechanism of action of thiamine-dependent enzymes. By employing this intermediate as a hydroxy-substituted N,S-ketene acetal, we successfully captured it via Claisen rearrangement towards the preparation of diaryl tertiary alcohol products that are isomers of the hitherto elusive intermediate. This strategy also constitutes an unusual disconnection for a Claisen rearrangement precursor.

We have also uncovered an unprecedented radical C-N bond scission of a Breslow intermediate when a fluorenyl group is installed on the azolium nitrogen atom. This facile homolysis affords intermediates that lead to products analogous to those previously reported by Oka. This method is useful for the preparation of several medicinally relevant 2-ketoazoles, while efforts are underway for its application towards the derivatization of existing azole drugs and medicinally relevant aldehydes.

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