Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Chemistry

Supervisor

Brian L. Pagenkopf

Abstract

The Mukaiyama oxidative cyclization has been a major area of study within the Pagenkopf group and within the field of THF containing natural products. This document contains a brief discussion of the major divisions of THF synthesis; SN2, cycloadditions, and transition mediated strategies. The development of the Mukaiyama cyclization is described from the earliest applications of cobalt acac type ligand in Mukaiyama’s work to the initial discovery of the cyclization reactivity. Initial finding from the Mukaiyama group is shown, accompanied by its applications to the synthesis of mucosin, aplysiallene, and bullatacin. Previous attempts at improved catalyst design are presented with characterization via x-ray crystallography.

The development of a novel (Z)-2-hydroxy-5,5-dimethyl-1-(4-methyl-1-piperazinyl)-2-Hexene-1,4-dione, water-soluble, ligand system for the Mukaiyama oxidative cyclization has been accomplished in an efficient and reproducible fashion. The ligand was utilized in cobalt catalyzed oxidative cyclizations of trans-tetrahydrofuran rings. Improved catalyst performance was discovered including; greater catalyst stability, higher product yield and simplified purification. Increased catalyst performance also allowed for an increased substrate scope as compared to earlier generations of the catalyst. Substrate scope exploration demonstrated that oxidizable positions were tolerated by the new catalyst. Discussion of subsequent applications of the Co(nmp)2 in total synthesis is also included.

Previous catalyst systems for the Mukaiyama cyclization proved unable to cyclize more highly substituted THF precursors. Under the cyclize conditions with Co(nmp) 2,various substrates were able to be cyclized to achieve new THF and oxime products. 2,2,5 tetrahydrofuran substitution patterns were explored and were accessible in moderate yields. Finally, the synthesis of cyclocapitelline is discussed to demonstrate the utility of cyclization conditions in synthesis.

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