Date of Graduation

8-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor

Nan Zheng

Committee Member

Matthias McIntosh

Second Committee Member

Neil Allison

Third Committee Member

Bill Durham

Keywords

Pure sciences; Carbon-carbon bond; Fused indolines; Organolithium chemistry; Tethered styrenes; Visible light photoredox catalysis

Abstract

Chemists worldwide have accepted the challenge of developing methods to access a variety of compounds as single enantiomers, including the use of enzymes, chiral auxiliaries, and resolutions. In particular, dynamic resolutions offer a unique way to access chiral compounds using a few controllable steps, including the variation of both time and temperature. Many groups have implemented this methodology to generate various polysubstituted pyrrolidines and piperidines, which are substructures ranking high on the list of nitrogen–containing pharmaceuticals.

The Gawley group revealed a catalytic dynamic resolution (CDR) of N–Boc–piperidine using a chiral ligand. Impressively, the chemistry was tolerant of a variety of electrophiles and generated the products with high enantioselectivity. However, due to unknown reasons, reproducibility emerged as an issue regarding this methodology. In this document, meticulous studies on factors that affect the CDR are discussed, including ligand purity, temperature studies, and impurity detection. Additionally, studies on the diastereoselective synthesis of α,α,α’–trisubstituted is presented, including 2D NMR data that aided in determining the relative configurations of select products.

Another focus was also pursued due to the unexpected passing of Dr. Bob Gawley. Visible light has recently emerged as a valuable reagent in the synthesis of organic molecules in the presence of a photoredox catalyst. This discovery has opened the doors for synthetic chemists to provide important molecules using sustainable methods.

Nan Zheng recently revealed an oxidative C–N bond–forming cascade of styrenyl anilines to yield a variety of substituted indoles using visible light photoredox catalysis. They proposed a benzylic cation intermediate that ultimately forms an indole by deprotonation in an E1 fashion. In this document, the synthesis of C2,C3 fused indolines is presented using a similar approach. Using styryl anilines tethered with a nucleophile, the benzylic cation intermediate was effectively trapped in a SN1 fashion to generate various fused indolines as single diastereomers. Additionally, detailed synthetic routes, including the challenges in substrate syntheses, as well as the limits of this photoredox cascade is presented.

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