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

职业：有机合成中过渡金属催化反应的计算研究

• 批准号: 1654122
• 负责人: Peng Liu
• 金额: $ 62.5万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1654122&HistoricalAwards=false
• 关键词: CAREER; Computational; Studies; Transition; Metal

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.

在这个由化学系化学结构、动力学和机理B项目资助的CAREER项目中，匹兹堡大学化学系的Peng Liu教授正在开发新的策略，利用计算工具来研究辅助配体在未活化起始材料（例如具有碳-碳和碳-氢键的材料以及未活化的材料）的过渡金属催化反应中的机制和影响。 烯烃。本研究的目的是揭示常见有机金属中间体在这些转化中的基本反应规则，并开发新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发挥计算能力，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，在交互式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应用商店免费向有机化学本科学生和公众发布。这项新技术可能会改变向非专家展示有机分子和反应的方式，并创建一种更有效的方法来促进对有机化学概念的理解。该项目旨在解决对过渡金属催化剂进行计算研究的两个基本挑战：1）对许多最近开发的催化系统缺乏机械理解，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。该研究研究了涉及 C-H 和 C-C 键断裂步骤后形成的活化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、环张力以及降冰片烯和路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的起源，开发了配体-底物相互作用模型。该模型使用能量分解分析 (EDA) 方法将空间配体-底物相互作用分解为具有化学意义的术语，包括空间排斥、极化、电荷转移和色散。从所提出的配体-底物相互作用模型中获得的见解用于开发过渡金属催化剂的催化剂筛选方法。 此外，该项目为合成化学研究人员建立了一个学习和使用计算工具来支持他们的科学研究的平台。该平台纳入了一系列活动，包括课程和培训材料开发、合作和学生交流，以及针对本科生中代表性不足的少数族裔学生的暑期研究项目。为具有合成有机背景的学生开发了基于发现的计算化学课程，以提供有机和计算化学界面的跨学科培训。研究活动产生的简单计算模型、软件工具、反应原理和在线配体数据库促进了合成有机化学家对计算工具的使用。

项目成果

Zirconium-Redox-Shuttled Cross-Electrophile Coupling of Aromatic and Heteroaromatic Halides.

• DOI: 10.1016/j.chempr.2021.06.007
• 发表时间: 2021-07-08
• 期刊: Chem
• 影响因子: 23.5
• 作者: Wu TF;Zhang YJ;Fu Y;Liu FJ;Tang JT;Liu P;Toste FD;Ye B
• 通讯作者: Ye B

Boron insertion into alkyl ether bonds via zinc/nickel tandem catalysis

• DOI: 10.1126/science.abg5526
• 发表时间: 2021-04-09
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Lyu, Hairong;Kevlishvili, Ilia;Dong, Guangbin
• 通讯作者: Dong, Guangbin

Compatibility Score for Rational Electrophile Selection in Pd/NBE Cooperative Catalysis.

• DOI: 10.1016/j.chempr.2020.09.004
• 发表时间: 2020-10-08
• 期刊: Chem
• 影响因子: 23.5
• 作者: Qi X;Wang J;Dong Z;Dong G;Liu P
• 通讯作者: Liu P

An enzymatic platform for the asymmetric amination of primary, secondary and tertiary C(sp3)–H bonds

• DOI: 10.1038/s41557-019-0343-5
• 发表时间: 2019-10
• 期刊: Nature Chemistry
• 影响因子: 21.8
• 作者: Yang Yang-Yang;I. Cho;X. Qi;Peng Liu;F. Arnold

The Thermal Rearrangement of an NHC‐Ligated 3‐Benzoborepin to an NHC‐Boranorcaradiene

NHC 的热重排 - 连接 3 - 苯并硼平与 NHC - 硼烷二烯

• DOI: 10.1002/ange.201912234
• 发表时间: 2019
• 期刊: Angewandte Chemie
• 作者: Shimoi, Masaki;Kevlishvili, Ilia;Watanabe, Takashi;Maeda, Katsuhiro;Geib, Steven J.;Curran, Dennis P.;Liu, Peng;Taniguchi, Tsuyoshi
• 通讯作者: Taniguchi, Tsuyoshi