College of Science and Health Theses and Dissertations

Date of Award

Spring 6-13-2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Quinetta Shelby, Ph.D.

Second Advisor

Paul Vadola, Ph.D.

Third Advisor

Caitlin Karver, Ph.D.

Abstract

Spirocycles are a class of molecules consisting of a quaternary atom al the junction of two fused rings. This structural motif is found in a number of biologically active natural products and pharmaceuticals. Current strategies to synthesize these structures include classical methods such as alkylation and rearrangement, as well as more modern methods reported in the past decade which utilize electrophilic halogen reagents. As part of our research interests in clectrophilic transition metal catalysts to effect powerful transformations, we developed the first redox-neutral spirocyclization of para-methoxy aryl alkynoate esters using homogeneous gold catalysis. The reaction proceeds at ambient temperature in dichloromethane with 5 mol % loading each of Au(PPh3)Cl catalyst and AgOTf activator. The addition of I equivalent of water

was found to be essential for the success of the reaction, playing a crucial role as a nucleophilc in

the proposed reaction mechanism. During our investigation ofthe substrate scope of the reaction, we found that substrates bearing various groups on the alkyne underwent spirocyclization in good lo excellent yields in short reaction limes. In addition, both electron-rich and electron­ deficient aromatic rings were well tolerated under these reaction conditions. However, substrates bearing strongly deactivating groups on the alkyne failed to react. Using our conditions, we were also able to directly access the tricyclic core of the antifungal compound perenniporide A, a spirocyclic secondary metabolite of Perenniporia sp., a fungus found in the Chinese medicinal plant Faliopiajaponica.

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