UCLA

This dissertation describes the study of heterocyclic arynes and their applications to synthetic organic chemistry. Heterocyclic arynes are highly reactive intermediates that undergo a variety of unique reactions. The ability to employ these intermediates in organic synthesis allows for the synthesis of substituted heterocyclic compounds. Chapter one reviews previous efforts in the area of hetaryne chemistry. Emphasis is placed on the chemistry of indolynes and pyridynes and applications to the synthesis of natural products. Chapters two and three discuss experimental studies involving indolyne intermediates. Chapter two pertains to the development of various indolyne precursors and studies of their reactivity using both experimental and computational methods. This culminates in an explanation for the observed regioselectivity of the indolyne intermediates. Chapter three covers the design of a substituted indolyne that reacts with an opposite sense of regioselectivity from the parent system and the use of this species in the synthesis of the natural product indolactam V. Chapter four describes a simple computational model for predicting the accessibility and preferred site of attack for a hetaryne intermediate that utilizes Density Functional Theory calculations. Also included is a comparison of predicted regioselectivities to experimental data from published examples. Chapter five discusses the development of a method for controlling the regioselectivity in reactions of 3,4-pyridynes. The use of substituted pyridyne derivatives allows for either product isomer to be obtained selectively. The directing group is used for subsequent functionalization. Chapter six pertains to the synthesis of the natural product tubingensin A. Our studies focus on the use of a carbazolyne intermediate for the introduction of the key vicinal quaternary centers of the natural product.