Beyond Acylation: New Methodology and Mechanistic Studies of Anhydrides for Stereoselective Synthesis

美国国家科学基金会化学部化学合成计划支持加州大学戴维斯分校化学系Jared Shaw教授实验室的这项研究项目。肖教授发现了新的反应，可以将简单的化学原料转化为复杂的分子，并控制其整体形状。为了实现这一目标，肖教授和他的学生正在探索三种尚未被探索的化学反应模式。它们都以一种新的方式使用了一种众所周知的分子片段——酸酐。新反应既包括新方法的发展，也包括对控制新反应速度和特异性的因素的探索。肖教授是戴维斯科学咖啡馆（Davis Science Cafe）的创始人，这是一个每月一次的活动，科学家们聚集在一起，向公众介绍他们的工作。该项目支持最大限度地发挥科学咖啡馆和其他外展活动的影响，并支持科学传播在北加州的传播。该项目还支持一系列推广活动，以实现各级科学教育的目标，包括参加小学的科学博览会，与初高中学生一起参加盲人化学营，以及在加州大学戴维斯分校复兴奇卡诺人/拉丁美洲人和美洲原住民科学促进会（SACNAS）。这项研究可能为化学工业提供新的、创新的方法和先进的制造机会。虽然酸酐的化学性质主要取决于它们作为亲电酰化剂的能力，但Shaw小组的新进展利用了这些化合物作为多功能亲核试剂的能力。这个项目正在寻求三个具体的调查途径。首先，将酸酐加到手性亚胺上显示出立体控制，这违反了羰基化合物所建立的规则。对这些反应结果的广泛调查与计算研究相结合，正在用于建立一个新的立体化学模型来描述亚胺在与软亲核试剂（即富电子烯烃）反应中的行为。其次，正在研究酸酐与新的亲电试剂的碱介导反应，如果可能的话，还在研究酸酐与新的亲电试剂的催化反应。这一努力包括合成一类新的手性催化剂，以及发展酸酐与缺电子烯烃和叠氮嘧啶之间的加成反应。第三，对酸酐烯醇硅烷的反应进行了研究。虽然这种化合物的数量很少，但肖小组已经发现了新的有机催化反应，这种反应可以用相同的亚胺亲电试剂导向至少两种不同的产物。这项研究补充了以前的工作，研究亚胺与酸酐的反应，提供了新的反应性，导致新的和有趣的产品。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Chemical Synthesis Program of the NSF Division of Chemistry supports this research project in the laboratory of Professor Jared Shaw in the Chemistry Department at the University of California, Davis. Professor Shaw discovers new reactions that enable simple, chemical starting materials to be converted into complex molecules with control of their overall shape. To accomplish this, Professor Shaw and his students are exploring three under explored modes of chemical reactivity. Each of these use a well-known molecular fragment, an anhydride, in a new way. The new reactions involve both the development of the new methods and an exploration of the factors that control the speed and specificity of the new reactions. Professor Shaw is the founding host of the Davis Science Cafe, which is a monthly event that brings scientists together to describe their work to the general public. This project support efforts to maximize the impact of the Science Cafe and other outreach events and bolster the spread of science communication in Northern California. This project also supports an array of outreach activities to achieve the goal of science education at all levels, including participation in a science fair at an elementary school, work with middle and high school students at Chemistry Camp for the Blind, and the revival of the Chapter of the Society for the Advancement of Chicanos/Latinos and Native Americans in Science (SACNAS) at UC Davis. This research may provide new, innovative approaches and advanced manufacturing opportunities for the chemical industry. Although the chemistry of anhydrides is dominated by their ability to serve as electrophilic acylating agents, new advances in the Shaw group exploit the ability of these compounds to serve as versatile nucleophiles. This project is pursuing three specific avenues of inquiry. First, the addition of anhydrides to alpha-chiral imines has shown stereocontrol that defy the rules established for carbonyl compounds. A broad investigation of the outcomes of these reactions paired with computational studies is being used to build a new stereochemical model to describe the behavior of imines in reactions with soft nucleophiles, i.e. electron-rich alkenes. Second, the base-mediated and, if possible, catalyzed reactions of anhydrides with new electrophiles are being studied. This effort involves the synthesis of a new class of chiral catalysts and the development of addition reactions between anhydrides and electron-deficient alkenes and aziridines. Third, the reactions of anhydride enol silanes is being nvestigated. Although a small number of these compounds have been made, the Shaw group has discovered new organocatalytic reactions that enable the reactivity to be steered toward at least two different products with the same imine electrophile. This investigation complements previous work examining the reactions of imines with anhydrides by providing novel reactivity leading to new and interesting products.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.