Date of Award

1993

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Richard D. Gandour

Abstract

Enzymes exhibit extraordinary efficiency and specificity in catalysis. A source of the catalytic power observed in enzymes has been attributed to the ability of the enzyme-substrate complex to bring the substrate into close proximity to the catalytic groups with proper orientation for reaction. However, the contributions of proximity and of orientation to the origin of catalytic power have not been quantified. A series of tethered and untethered 2,2$\sp\prime,$6,6$\sp\prime$-tetrasubstituted diarylethynes have been proposed to study the effect of proximity of the catalytic group to the substrate on catalysis. The syntheses of the diarylethyne models require efficient procedures for the synthesis of 2,6-disubstituted arylethynes and unsymmetrical 2,2$\sp\prime,$6,6$\sp\prime$-tetrasubstituted diarylethynes. A literature search for the preparation of mono- and diarylethynes has revealed no examples of 2,6-disubstituted arylethynes with oxygen substituents or unsymmetrical 2,2$\sp\prime,$6,6$\sp\prime$-tetrasubstituted diarylethynes. The methodology developed for synthesizing these mono- and diarylethynes serves as a basis for synthesizing the models. Two procedures have been developed for the synthesis of arylethynes. The first method involves a modification of a classic procedure for synthesizing arylethynes from acetophenones. The second procedure involves a palladium-mediated coupling of aryl iodides with trimethyl ((trimethylsilyl)ethynyl) stannane, followed by cleaving the trimethylsilyl group. The advantages and disadvantages of these procedures are discussed. Six new arylethynes have been synthesized by these methods. Unsymmetrical diaryl- and arylnaphthylethynes have been synthesized by palladium-mediated coupling of arylethynes with aryl triflates or halides. The arylnaphthylethynes serve as precursors to another series of models, which have different distances and orientations between the functional groups, to test proximity on catalysis. A close precursor to the untethered diarylethyne, 2- (2-methoxy-6-(methoxymethoxy)-phenylethynyl) -3-methoxybenzoate, was synthesized. One pathway for the synthesis of the tethered models has been eliminated; however, three additional pathways are proposed. The ortho-substituted functional groups of the 2,2$\sp\prime,$6,6$\sp\prime$-tetrasubstituted diarylethynes react with ethyne to form three heterocycles. The robust chemistry of the demethylation and lactonization of the diarylethynes provides an easy entry to unusual and highly substituted 2-arylbenzofurans, 3-arylbenzopyranones, and 3-benzylideneisobenzofuranones.

Pages

143

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