Reactivity and Lone Pairs: Proton Transfer and Stereoelectronic Effects

这项有机和大分子化学项目的拨款属于有机反应动力学的子领域，并支持加州大学圣地亚哥分校Charles Perrin博士的研究，研究非成键电子对及其空间取向对化学反应基本方面的影响，如质子转移速率和立体电子效应。理解这些效应和超快机械过程的速率是很重要的，因为它们的累积效应在宏观世界中被认为是较慢的化学反应。氮或氧孤对的可用性促进了在皮秒时间尺度上发生的快速质子转移，以及其他重要过程，如扩散、单键旋转和溶剂重组。根据目前的立体电子控制理论，当孤对与离去基或进入的亲核试剂反周平面时，反应性会增加，但最近的实验结果对这种概化提出了质疑。第一个研究领域是继续分析酰胺中的质子交换过程和铵离子中的旋转过程，以探索氢键在溶剂化离子中的作用。广泛使用现代核磁共振仪器，它允许在平衡条件下质子交换动力学的测量。这里的一个重点将是底物选择性和位置选择性的现象，在遇到控制质子从脒离子转移到氢氧化物。证据将寻求一个迄今未报道的协调机制的胺催化质子交换在水中。在第二个研究领域，将尝试确定孤对和反应键之间的首选立体化学关系。实验系统将包括甲氧基交换动力学在邻位酯和酰胺缩醛，脱水在外聚氨基烯丙醇。另一种方法将涉及对偕胺离子和胍的水解产物的研究，以及对偕胺、咪托铵和偕胺离子与亲核试剂反应的研究。这些实验旨在阐明立体电子控制可能起作用的条件，以及它对增加反应性的贡献有多大。

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.