Ketone Alkylation Using Simple Olefins: A Sustainable Chemistry Approach

使用简单烯烃进行酮烷基化：一种可持续的化学方法

• 批准号: 1855556
• 负责人: Guangbin Dong
• 金额: $ 48.5万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1855556&HistoricalAwards=false
• 关键词: Ketone; Alkylation; Using; Simple; Olefins

Supported by the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Guangbin Dong of the University of Chicago is leading a team of researchers to invent new ways to make carbon-carbon bonds. Carbon-carbon bonds are an essential part of almost all organic chemicals. These important bonds form the backbone of most medicines and plastics (polymers) and thus are produced on massive scales. Dr. Dong?s research focuses on forming carbon-carbon bonds from simple, inexpensive and non-toxic stating materials without also producing by-products which must be separated and/or discarded. This approach follows the principles of ?Green Chemistry? in that the new synthetic routes to commodity and specialty chemicals are more environmentally friendly. The research grant also supports the education of students at many levels. Professor Dong is actively engaged in the "ChiS&E" program to provide early chemistry education to Chicago public middle-school students. He is also involved in the Collegiate Scholars Program to teach high school students and the Leadership Alliance Summer Research Early Identification Program (SR-EIP) to offer laboratory research experiences to undergraduate students. These outreach activities encourage a diverse group students to explore careers in science and engineering while learning and actively contributing to research.The goal of this project is to develop byproduct-free ketone-olefin coupling reactions via transition metal (TM)-catalyzed carbon-hydrogen (C-H) bond activation. These approaches could serve as more environmentally-friendly approaches to access alkylated ketones. The research plan employs bifunctional templates to enable enamine/TM or imine/TM cooperative catalysis. The team's objectives are first, to develop a direct branched-selective alpha-alkylation of ketones with simple olefins via enamine/TM cooperative catalysis and second, to develop a direct alkylation of ketones with simple olefins via imine/TM cooperative catalysis. Carbonyl functionalization plays a central role in organic synthesis. Enolate alkylation and conjugate (alkyl) addition represent two common and important approaches for introducing alkyl groups at carbonyl positions.. Notably, these reactions are not economically- or environmentally-friendly processes mainly due to the use of stoichiometric halogen-based alkylating agents and/or stoichiometric organometallic species. Here, Professor Dong and his team employ a TM-catalyzed enamine or imine-mediated C-H functionalization strategy to achieve ketone alkylation using simple unactivated olefins as the alkylating agents. This approach is considered more sustainable than current methods because stoichiometric by-products are not generated and the reaction conditions are generally pH- and redox-neutral, thereby tolerating a broad range of functional groups. From a practical viewpoint, olefins are typically a cheaper and more readily available feedstock than the corresponding alkyl halides or organometallic species. Byproduct-free ketone alkylation methods using regular olefins as the alkylating agents are developed through the new bifunctional catalysts. Professor Dong and his team are engaged in several outreach activities, including introducing grade school students to chemical concepts. Integrating educational activities of students from diverse age groups and backgrounds into the existing research program has been a primary goal of the research group.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.

在化学系化学合成（SYN）项目的支持下，芝加哥大学的董广斌教授正在带领一组研究人员发明制造碳-碳键的新方法。 碳-碳键是几乎所有有机化学品的重要组成部分。这些重要的键构成了大多数药物和塑料（聚合物）的支柱，因此可以大规模生产。 董博士的研究重点是用简单、廉价且无毒的材料形成碳-碳键，同时不会产生必须分离和/或丢弃的副产物。这种方法遵循“绿色化学”的原则。因为商品和特种化学品的新合成路线更加环保。研究补助金还支持多个层次的学生教育。 董教授积极参与“ChiS&E”项目，为芝加哥公立中学生提供早期化学教育。 他还参与了教授高中生的大学学者计划和领导力联盟夏季研究早期识别计划（SR-EIP），为本科生提供实验室研究经验。这些外展活动鼓励多元化的学生在学习和积极参与研究的同时探索科学和工程领域的职业生涯。该项目的目标是通过过渡金属 (TM) 催化的碳-氢开发无副产物的酮-烯烃偶联反应(C-H)键活化。 这些方法可以作为获取烷基化酮的更环保的方法。该研究计划采用双功能模板来实现烯胺/TM或亚胺/TM协同催化。该团队的目标首先是通过烯胺/TM协同催化开发酮与简单烯烃的直接支链选择性α-烷基化，其次是通过亚胺/TM协同催化开发酮与简单烯烃的直接烷基化。羰基官能化在有机合成中起着核心作用。烯醇化烷基化和共轭（烷基）加成是在羰基位置引入烷基的两种常见且重要的方法。值得注意的是，这些反应不是经济或环境友好的过程，主要是由于使用化学计量的基于卤素的烷基化剂和/或化学计量的有机金属物质。在这里，董教授和他的团队采用TM催化的烯胺或亚胺介导的C-H官能化策略，使用简单的未活化烯烃作为烷基化剂来实现酮烷基化。这种方法被认为比目前的方法更具可持续性，因为不会产生化学计量的副产物，并且反应条件通常为 pH 和氧化还原中性，从而可耐受多种官能团。 从实际角度来看，烯烃通常是比相应的烷基卤化物或有机金属物质更便宜且更容易获得的原料。通过新型双功能催化剂开发了使用常规烯烃作为烷基化剂的无副产物的酮烷基化方法。董教授和他的团队从事多项外展活动，包括向小学生介绍化学概念。 将来自不同年龄段和背景的学生的教育活动融入现有的研究计划一直是该研究小组的首要目标。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查进行评估，认为值得支持标准。

项目成果

Intramolecular β-Alkenylation of Cyclohexanones via Pd-Catalyzed Desaturation-Mediated C(sp 3 )–H/Alkyne Coupling

通过 Pd 催化去饱和介导的 C(sp 3 )–H/炔烃偶联进行环己酮的分子内 β-烯基化

• DOI: 10.1021/jacs.0c02654
• 发表时间: 2020-05
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Wang, Chengpeng;Naren, Nevin A.;Zheng, Pengfei;Dong, Guangbin
• 通讯作者: Dong, Guangbin

FMPhos: Expanding the Catalytic Capacity of Small-Bite-Angle Bisphosphine Ligands in Regioselective Alkene Hydrofunctionalizations

FMPhos：扩大小咬角双膦配体在区域选择性烯烃氢官能化中的催化能力

• DOI: 10.1021/acscatal.0c04199
• 发表时间: 2020-11-24
• 期刊: ACS Catalysis
• 影响因子: 12.9
• 作者: Xiao;Xukai Zhou;Jianchun Wang;Guangbin Dong
• 通讯作者: Guangbin Dong

Platinum‐Catalyzed α,β‐Desaturation of Cyclic Ketones through Direct Metal–Enolate Formation

铂 — 通过直接形成金属 — 烯醇化物催化环酮的 α,β 去饱和

• DOI: 10.1002/anie.202013628
• 发表时间: 2021-02
• 期刊: Angewandte Chemie International Edition
• 作者: Chen, Ming;Dong, Guangbin
• 通讯作者: Dong, Guangbin

Development and Mechanistic Studies of the Iridium‐Catalyzed C−H Alkenylation of Enamides with Vinyl Acetates: A Versatile Approach for Ketone Functionalization

铱催化烯酰胺与乙酸乙烯酯的 C-H 烯基化反应的开发和机理研究：酮官能化的多功能方法

• DOI: 10.1002/anie.202107331
• 发表时间: 2021-08
• 期刊: Angewandte Chemie International Edition
• 作者: Zhou, Bo;Qi, Xiaotian;Liu, Peng;Dong, Guangbin
• 通讯作者: Dong, Guangbin

Branched‐Selective Direct α‐Alkylation of Cyclic Ketones with Simple Alkenes

环酮与简单烯烃的支链选择性直接α烷基化

• DOI: 10.1002/anie.201900301
• 发表时间: 2019-02
• 期刊: Angewandte Chemie International Edition
• 作者: Xing, Dong;Qi, Xiaotian;Marchant, Daniel;Liu, Peng;Dong, Guangbin
• 通讯作者: Dong, Guangbin