Regardless of the acid employed to promote the pinacol-terminated Prins cyclization of allylic silyl ether 13, the selective formation of either carbocyclic products is possible. Cyclopentanone 14 is isolated when the reaction is performed in a non-polar reaction medium, while 12 is isolated when an aqueous solvent system is utilized. It is proposed that this reactivity can be attributed to the stereoelectronic effects that the allylic substituents exert on the nucleophilicity of the terminal alkene in the early and late transition states of the Prins cyclization. A shift from an early to a late transition state can be achieved through the use of an aqueous reaction medium, thereby effecting the reversal in stereoselectivity that is observed. The rearrangement of acetal 29 displays the same pattern in reactivity, as both heterocyclic products, 30 and 31, may be selectively isolated depending upon whether or not an aqueous solvent is employed. Aside from shedding further light upon our mechanistic understanding of the Prins-pinacol reaction, this study expands upon our model for stereoselection and increases its predictive power. This experimental link between solvent and stereoselectivity enhances the synthetic utility and scope of this already powerful tandem reaction sequence.

submitted in partial satisfaction of the requirements

for the degree of

MASTER OF SCIENCE

in chemistry

Thesis Committee:

Professor Larry E. Overman, Chair

Professor Scott D. Rychnovsky

Professor David L. Van Vranken

2005