The C-F bond as a tool in predicting the conformational preference of organic molecules

Abstract

Chapter One highlights the history and development of organofluorine chemistry. Later sections highlight the introduction of fluorine into organic molecules as an important tool in modifying their physical, chemical and biological properties. The significance of fluorine substitution is further explored by exemplifying its role in medicinal chemistry. Chapter Two introduces the importance of stereoelectronic effects on the conformational preference of organic molecules. The implications of the gauche effect and, in particular, the fluorine-gauche effect are discussed. Chapter Three presents results which demonstrate the influence of the C-F bond in the β- fluoroamide gauche effect and an α -fluoroamide cis effect. The presence of a fluorine atom (β-to an ester oxygen also reveals the influence of a (β -fluoroester) gauche effect. Chapter Four presents ab initio calculations used to investigate the gauche effect in protonated 2-fluoroethanol and 2-fluoroethylamine. It is noted that the (β-fluoroethylammonium ion is the largest conformational gauche preference yet measured whereas its neutral counterpart, fluoroethylamine, does not exhibit a measurable gauche preference.