Stereoselectivities of Synthetic Organic Reactions

描述（由申请人提供）：本研究项目的目标是开发和应用最先进的计算方法来理解立体选择性，并帮助设计新的立体选择性试剂和催化剂。立体选择性的控制是高效合成的一个基本特征，目前已经开发出许多控制立体化学的精细程序。这些都是合成有效药物制剂的关键因素。GM36700的更新是建立在上一个拨款期的成就之上的。与世界各地许多合成实验室的合作使我们的注意力集中在有机合成进展的核心问题上。该基金已成为大量研究生、博士后和来自合成小组的实验室访客的培训工具，这些人已成为有机化学和药物化学计算理解的领导者。新资助期的具体目标是：目标1：发展量子力学方法，为大分子和柔性分子的立体选择性提供准确的预测。需要在计算方法和应用方面取得许多进步，才能使这些方法对重要的有机反应进行实时探索。目标2：不对称有机催化的探索和新催化剂的预测和测试。许多有机催化剂已经被发现，并将在理论上进行研究。新设计的催化剂将由我们或我们的合作者进行研究。目的3：探索过渡金属催化的不对称反应。Rh、Mo、Ru、Pd和ni催化的氢化、烯丙基取代和不对称偶联反应的研究将增加对立体选择反应的过渡金属催化起源的认识。目标4：协同设计和测试立体选择反应的新试剂和催化剂。正在进行的与许多合成有机化学家和其他合作者的合作可能在下一个资助期发展，推动新技术的发展和对立体选择性的了解的增加。

DESCRIPTION (provided by applicant): The goal of this research program is to develop and apply state-of-the-art computation methods to understand stereoselectivity and to aid in the design of new stereoselective reagents and catalysts. The control of stereoselectivity is an essential feature of efficient synthesis, and many elegant procedures for the control of stereochemistry have been developed. These are critical elements in the synthesis of effective pharmaceutical agents. This renewal of GM36700 is built on the achievements of the last grant period. Collaborations with many synthetic laboratories around the world have kept our attention focused on problems that are central to progress in organic synthesis. The grant has been a training vehicle for a large number of graduate students, postdocs, and visitors to our laboratories from synthetic groups, and these people have become leaders in computational understanding of organic and pharmaceutical chemistry. The specific aims for the new grant period are: Aim 1: Development of quantum mechanical methods to provide accurate predictions of stereoselectivity for large and flexible molecules. Many advances in computational methods and applications are needed to make these practical for the real-time exploration of important organic reactions. Aim 2: Explorations of asymmetric organocatalysis and predictions and testing of new catalysts. Many organocatalysts have been discovered and will be studied theoretically. Newly designed catalysts will be studied by us or our collaborators. Aim 3: Exploration of transition metal catalyzed asymmetric reactions. Studies of Rh, Mo, Ru, Pd, and Ni-catalyzed hydrogenations, allylic substitutions, and asymmetric coupling reactions will increase knowledge of the origins of transition metal catalysis of stereoselective reactions. Aim 4: Collaborative design and testing of new reagents and catalysts for stereoselective reactions. Ongoing collaborations with many synthetic organic chemists and other collaborators likely to develop during the next grant period drive the development of new technology and the increase in understanding of stereoselectivity.