Date of Graduation

7-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor

Mattias C. McIntosh

Committee Member

Nan Zheng

Second Committee Member

Neil Allison

Third Committee Member

James F. Hinton

Keywords

Pure sciences; Cross-coupling; Dynamic resolution; Organolithium

Abstract

My former boss, Dr. Gawley, always loved to say, “The world is chiral” (à la Pasteur). From DNA and proteins to hands and feet, it is obviously true. Also, a wide variety of chemical products exist as single enantiomers. Advances in chemical technology have greatly accelerated asymmetric synthesis in the past quarter century, and namely, organolithiums, have been shown to provide a versatile route to chiral natural products and biologically active molecules. Versatility arises from the array of methods that produce a chiral organolithium. Dynamic thermodynamic resolution (DTR) is considered one of the most practical methods, but among the others are asymmetric deprotonation and tin-lithium exchange. The selected targets for this investigation using chiral organolithiums, 2,3-dehydropyridones and chiral tertiary alcohols, are important building blocks for enantioselective synthesis. Practicality ultimately begins and ends with cost efficiency, and catalysis is generally a good place to start. Catalytic dynamic resolution (CDR), as well as conventional transition metal-catalyzed cross-coupling, has been applied with the intention of expanding the scope of organolithiums in asymmetric synthesis. The dynamic resolution of the ethylene and propylene ketal of N-Boc-2-lithio-4-oxopiperidine was investigated and resulted in a number of novel piperidine derivatives, and arylation of alkyl and benzyl carbamates via Negishi and Stille-type cross-coupling gave a number of novel tertiary alcohol precursors.

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