Reactivity and Lone Pairs: Proton Transfer and Stereoelectronic Effects

有机和高分子化学项目的这项拨款是在有机反应动力学的子领域，并支持加州大学圣地亚哥分校的Charles Perrin博士研究非键电子对及其空间取向对化学反应的基本方面的影响，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，因为在宏观世界中，它们的累积效应被认为是较慢的化学反应。氮或氧孤对的存在促进了质子的快速转移，发生在皮秒时间尺度上，以及其他重要的过程，如扩散、围绕单键的旋转和溶剂重组。根据目前的立体电子控制理论，当一个孤立的对与离开的基团或进入的亲核试剂反周面时，反应性会增加，但最近的实验结果对这一推广提出了质疑。第一个研究领域是继续对酰胺中的质子交换过程和氨离子中的旋转过程进行分析，以探索氢键在溶剂化离子中的作用。现代核磁共振仪器被广泛使用，它可以测量平衡条件下的质子交换动力学。这里的焦点将是在相遇受控的质子从胺离子到氢氧化物的转移中的底物选择性和位置选择性现象。将寻找迄今未报道的胺催化水中质子交换的协调机制的证据。在第二个研究领域，将尝试确定孤立对和反应键之间的首选立体化学关系。实验系统将包括原酯和酰胺缩醛中的甲氧基交换动力学，以及表观伽马氨基烯丙醇中的脱水动力学。另一种方法将包括对酰胺离子和胍类离子的水解，以及酰胺离子、咪达通离子和亚胺离子与亲核试剂的反应的产物研究。这些实验旨在阐明立体电子控制可能起作用的条件，以及它在多大程度上有助于提高反应性。

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.