Date of Award


Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)



First Advisor

Michael A. McKinney

Second Advisor

Daniel T. Haworth

Third Advisor

William A. Donaldson

Fourth Advisor

Sheldon E. Cremer

Fifth Advisor

Jeffrey Zalon


The nucleophilic ring opening of electron-deficient (electrophilic) cyclopropanes has found application in organic synthesis, the utility being greatly enhanced by the increased reactivity of spiroactivated cyclopropyl ring systems. Mechanistically the reaction is of fundamental importance being related to the Michael reaction of activated alkenes and nucleophilic substitution at saturated carbon. For this reason a comprehensive mechanistic and kinetic investigation of the nucleophilic cleavage of spiroactivated cyclopropanes was undertaken. The ring opening reaction with nucleophiles was studied using uv spectroscopy, employing pseudo-first-order kinetics. The reaction was found to be second-order and reversible under certain conditions. This reversibility provided a unique opportunity for obtaining the rates and equilibria parameters vital to this study. This reaction can also be viewed as an analog of the Menschutkin reaction for which the transition state structure is a matter of controversy. In probing the transition state structure of this system, activation parameters, extended Bronsted correlations, solvent effect, and Hammett (rho)(sigma) correlations were employed. An effort was also made to sort out the structure-reactivity relationships provided by this system. For the reaction with the nucleophiles employed (generally substituted pyridines and cyclic secondary amines), a dipolar transition state is proposed in which the carbon-carbon bond breaking lies well ahead of the carbon-nitrogen bond making with extensive solvent reorganization having occurred at the negative end of the dipolar structure. The mechanism of the reaction was further probed through a stereochemical study in which an optically pure enantiomer of a spiroactivated cyclopropane was synthesized and subjected to various stereochemical tests. For the compound utilized, the reaction proceeded with inversion of configuration and without evidence of racemization. Of interest in studying this reaction system, were the chemical properties of the resulting products. Being dipolar in nature, an acidic site is present. The acidity of this site was determined, and was found to have a considerably lower pKa, relative to Meldrum's acid. Having gained some useful insight into the characteristics of this reaction system through an extensive kinetic, mechanistic, stereochemical, and product analysis, a foundation has been layed for understanding the synthetic utility of the nucleophilic cleavage of cyclopropanes.



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