This grant in the Organic and Macromolecular Chemistry Program is in the subfield of organic reaction dynamics, and supports research of Dr. Charles Perrin, University of California at San Diego, into the effects of non-bonding electron pairs and their spatial orientation on basic aspects of chemical reactivity such as proton transfer rates and stereoelectronic effects. It is important to understand these effects and the rates of ultrafast mechanistic processes, since it is their cumulative effect that is perceived in the macroscopic world as slower chemical reactions. The availability of nitrogen or oxygen lone pairs facilitates rapid proton transfer, occurring on a picosecond time scale, along with other important processes such as diffusion, rotation about single bonds, and solvent reorganization. According to current theories of stereoelectronic control, reactivity is increased when a lone pair is antiperiplanar to a leaving group or to an incoming nucleophile, but recent experimental results raise questions about this generalization. The first research area is a continuation of ongoing analyses of proton exchange processes in amides and of rotation in ammonium ion, in order to probe the role of hydrogen bonding in solvating ions. Extensive use is made of modern NMR instrumentation, which permits measurement of proton exchange kinetics under equilibrium conditions. A focal point here will be the phenomena of substrate selectivity and positional selectivity in encounter-controlled proton transfer from amidinium ions to hydroxide. Evidence will be sought for a heretofore unreported concerted mechanism for amine-catalyzed proton exchange in water. In a second research area, attempts will be made to determine the preferred stereochemical relationship between lone pairs and reacting bonds. Experimental systems will include kinetics for methoxy exchange in ortho esters and amide acetals, and of dehydration in epimeric gamma-amino allylic alcohols. An alternative approach will involve product studies in the hydrolysis of amidinium ions and guanidines, and in the reactions of amidinium, imidatonium, and iminium ions with nucleophiles. These experiments are designed to clarify the conditions under which stereoelectronic control might be operative and how much it contributes to increased reactivity.
