CAREER: Computational Studies of Transition Metal Catalyzed Reactions in Organic Synthesis

在这个由化学系化学结构、动力学机制B项目资助的CAREER项目中，匹兹堡大学化学系的刘鹏教授正在开发新的策略，利用计算工具研究辅助配体在过渡金属催化的未活化起始材料（如具有碳-碳和碳-氢键的材料和未活化的烯烃）反应中的机制和作用。本研究的目标是揭示这些转换中常见的有机金属中间体的基本反应性规则，并开发新的模型来解释配体对反应性和选择性的影响。该项目的教育和推广计划旨在最大限度地提高计算能力，以加强有机化学概念的学习，并促进合成有机化学研究。刘教授的团队开发虚拟现实（VR）软件和教育材料，以在互动和沉浸式环境中可视化三维分子结构和反应机制视频。 VR软件及其教育模块通过Android和Apple应用程序商店免费向本科有机化学学生和公众发布。这项新技术可能会改变有机分子和反应呈现给非专业人士的方式，并创造一种更有效的方法来促进对有机化学概念的理解。该项目旨在解决过渡金属催化剂计算研究中的两个基本挑战：1）在许多最近开发的催化体系中缺乏机械理解，以及2）分析和合理化计算数据的复杂性，特别是配体效应的起源。研究了C-H键和C-C键断裂后形成的活性有机金属中间体的新反应途径，并阐明了配体、导向基团、取代基、环张力以及环己烯和刘易斯酸助催化剂的影响。为了系统地表征配体对反应性和选择性的影响，建立了配体-底物相互作用模型。该模型使用能量分解分析（EDA）方法将贯穿空间的配体-基底相互作用分解成化学上有意义的术语，包括空间排斥、极化、电荷转移和分散。从所提出的配体-底物相互作用模型获得的见解被用于开发过渡金属催化剂的催化剂筛选方法。 此外，该项目还为合成化学研究人员建立了一个学习和使用计算工具的平台，以支持他们的科学研究。一系列活动，包括课程和培训材料的开发，合作和学生交流，以及针对本科生代表性不足的少数民族学生的夏季研究计划，都纳入了该平台。为有机合成背景的学生开发了一门基于发现的计算化学课程，以提供有机化学和计算化学接口的跨学科培训。直接的计算模型，软件工具，反应性的原则，以及从研究活动中产生的在线配体数据库促进了合成有机化学家使用计算工具。

In this CAREER project funded by the Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division, Professor Peng Liu of the Department of Chemistry at the University of Pittsburgh is developing new strategies to use computational tools to investigate mechanisms and effects of ancillary ligands in transition-metal-catalyzed reactions of unactivated starting materials, such as materials with carbon-carbon and carbon-hydrogen bonds and unactivated olefins. The goal of this research is to reveal the fundamental reactivity rules of common organometallic intermediates in these transformations and to develop new models to interpret ligand effects on reactivity and selectivity. This project's educational and outreach plan aims to maximize the power of computations to enhance learning of organic chemistry concepts and to facilitate synthetic organic chemistry research. Professor Liu's team develops virtual reality (VR) software and educational materials to visualize three-dimensional molecular structures and reaction mechanism videos in an interactive and immersive environment. The VR software and its educational modules are released to undergraduate organic chemistry students and the general public free of charge through Android and Apple app stores. This new technology may transform the way organic molecules and reactions are presented to non-experts and create a more effective approach to advance understanding of organic chemistry concepts.This project aims to address two basic challenges in performing computational studies on transition metal catalysts: 1) the lack of mechanistic understandings in many recently developed catalytic systems, and 2) the complexities in analyzing and rationalizing computational data, in particular, the origin of ligand effects. The research investigates novel reaction pathways involving the activated organometallic intermediates formed after the C-H and C-C bond cleavage steps, and elucidates the effects of ligands, directing groups, substituents, ring strain, and norbornene and Lewis acid co-catalysts. To systematically characterize the origin of ligand effects on reactivity and selectivity, a ligand-substrate interaction model is developed. This model uses energy decomposition analysis (EDA) methods to dissect the through-space ligand-substrate interactions into chemically meaningful terms, including steric repulsion, polarization, charge transfer, and dispersion. The insights obtained from the proposed ligand-substrate interaction model are used to develop of a catalyst screening methodology for transition metal catalysts. In addition, this project establishes a platform for synthetic chemistry researchers to learn and use computational tools to support their scientific research. A spectrum of activities,including curriculum and training materials development, collaboration and student exchange, and summer research programs that target undergraduate underrepresented minority students, are incorporated in the platform. A discovery-based computational chemistry course for students with synthetic organic backgrounds is developed to provide an interdisciplinary training at the interface of organic and computational chemistry. The straightforward computational models, software tools, principles of reactivity, and the online ligand database resulting from the research activities facilitate the use of computational tools by synthetic organic chemists.