Asymmetric Lewis Base Catalysis in Main Group Chemistry

描述(由申请人提供)：本提案的主要目的是：(1)演示Lewis酸的Lewis碱激活(古特曼电子密度极化)的概念，因为它适用于主族中16和17族中的亲电物种，(2)开发尚未实现催化的经典主族反应的催化变体，(3)了解目标反应的结构/反应性相关性和获得高催化活性(周转频率和周转次数)的规则，(4)设计具有高立体选择性和高化学转化率的手性Lewis碱，以引入新的碳和杂原子取代的立体中心；(5)对下述新发明的催化反应进行详细的机理研究(动力学、光谱、结晶学、计算)。第一个主要工作将是开发16和17族亲电试剂最常见的反应的催化、对映体选择性变体。直接官能化和环官能化是合成立体定义的链、杂环和碳环的有效方法。这些反应是由亲电试剂硫(II)、氯(I)、溴(I)和碘(I)有效地引发的。设计路易斯碱来催化和控制结构和对映体的选择性将构成该计划的主要组成部分。第二个主要活性是合成富含对映体的含硫产物。除了众所周知的功能操作外，还将开发利用过渡金属催化偶联和直接配体偶联反应的C-S键的新的、立体控制的、建设性的取代反应。第三个主要工作将是发明、开发和探索一种新的Lewis碱催化反应亚类，该反应使用更高氧化态的碘(III)试剂来形成碳-碳键。碘盐的配体偶联反应的催化作用是前所未有的，并将被用于构建对映体富集芳基、烯基、炔基以及潜在的芳基取代酮和酯。 与公众健康相关：这项研究计划旨在开发一类主要组元素硫、氯、溴和碘在不同氧化态下的全新催化反应。路易斯碱激活这些元素的亲电性的能力的概念基础几乎具有无限的潜力。在美国，每年生产的价值近1万亿美元的商品已经涉及到催化作用，我们的贡献是用于目前还没有催化过程的化学反应。

DESCRIPTION (provided by applicant): The primary objectives of this proposal are: (1) to demonstrate the concept of Lewis base activation of Lewis acids (Gutmann electron density polarization) as it applies to electrophilic species in Groups 16 and 17 in the Main Group, (2) to develop catalytic variants of classical main group reactions for which catalysis has yet to be realized, (3) to learn the structure/reactivity correlations and the rules for achieving high catalytic activity (turnover frequencies and turnover numbers) for the target reactions, (4) to design chiral Lewis bases that will impart high stereoselectivity and high chemical conversion for the introduction of new carbon and heteroatom substituted stereocenters, and (5) carry out detailed mechanistic (kinetics, spectroscopic, crystallographic, computational) investigations of the newly-invented catalytic reactions described below. The first major effort will be the development of catalytic, enantioselective variants of the most common reactions of electrophilic Group 16 and 17 reagents. Direct functionalization and cyclofunctionalization of alkenes bearing a tethered nucleophile (oxygen, nitrogen, carbon) is a powerful method for creating stereodefined chains, heterocycles and carbocycles. These reactions are efficiently initiated by electrophilic sulfur(II), chlorine(I), bromine(I), and iodine(I) reagents The design of Lewis bases to catalyze and control the constitutional and enantiofacial selectivity will constitute a major component of this program. The synthetic manipulation of the enantiomerically enriched, sulfur-containing products constitutes the second major activity. In addition to well-known functional manipulations, new, stereocontrolled, constructive replacements of the C-S bond that employ transition metal catalyzed coupling and direct ligand coupling reactions will be developed. A third major effort will be the invention, development, and exploration of a new subclass of Lewis base catalyzed reactions that employs higher oxidation state iodine(III) reagents for carbon-carbon bond formation. Catalysis of the ligand coupling reaction of iodonium salts is unprecedented and will be investigated for the construction of enantiomerically enriched ?-aryl, ?-alkenyl, ?-alkynyl, and also potentially ?-aryl substituted ketones and esters. PUBLIC HEALTH RELEVANCE: This research proposal aims to develop a fundamentally new class of catalytic reactions of the main group elements, sulfur, chlorine, bromine, and iodine in various oxidation states. The conceptual foundation for the ability of Lewis bases to activate the electrophilic character of these elements has almost unlimited potential. Already, catalysis is involved in the processing of nearly a trillion dollars worth of goods produced annually in the US, and our contribution is for chemical reactions for which there is currently no catalytic process.