New Frontiers in Chemical Reactivity Via Catalytic Hydrogen Atom Transfer

通过催化氢原子转移实现化学反应的新领域

• 批准号: 10608144
• 负责人: Julian G West
• 金额: $ 36.84万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608144
• 关键词: Alcohols; Alkenes; Amines; Architecture; Area; Aziridines; Chemicals; Complex; Cues; Data; Development; Electrons; Elements; Enzymes; Epoxy Compounds; Goals; Health; Human; Hydrogen; Hydrogenation; Isotopes; Mentors; Methodology; Methods; Molecular; Movement; Mutase; Nature; Process; Protons; Reaction; Reagent; Research; Source; System; Translating; Vitamin B 12; Work; career; catalyst; dehydrogenation; desaturase; design; frontier; functional group; methyl group; salen; unsaturated bonds

PROJECT SUMMARY Hydrogen atom transfer (HAT), or the movement of one proton and one electron simultaneously, is an increasingly important element in synthetic methodology. While nature has made extensive use of HAT steps in processes such as those performed by desaturase and mutase enzymes, synthetic chemists are just beginning to realize the potential of this powerful, radical transformation. This MIRA proposal describes two important new areas enabled by HAT that the PI will explore over the next 5 years: modular radical hydrogenation and transpositional functionalization. The PI is prepared to make an impact in this important field from his mentored career, where he designed catalytic dehydrogenation and dehydroformylation systems functioning via HAT. The first area of research concerns development of a modular, stereoselective hydrogenation system able to completely control the configuration and isotopic composition at each reduced center (Project 1). Preliminary work by the PI has demonstrated radical hydrogenation can be achieved using cooperative hydrogen atom transfer (cHAT), a mechanism where each hydrogen atom arrives from a separate catalyst, allowing for each catalyst to be modified independently. One goal of this project is independent stereocontrol of each new stereocenter though use of two asymmetric catalysts (Project 1a). This design will allow for enantioselective anti- reduction, a currently impossible transformation. A simultaneous, independent goal builds on preliminary data showing each catalyst receives its hydrogen atom from an orthogonal source, permitting different isotopes to be predictably delivered in the same reaction (Project 1b). Together, this project area will provide a method to install H, D, or T in any configuration starting from an unsaturated bond, selecting between all possible isotopologues and stereoisotopomers via catalyst and reagent control. The second research area focuses on the development of new mustase-like reactions, where functionality is regioselectively transposed in a 1,2-fashion to remodel molecular architectures (Project 2). However, unlike mutase enzymes, these methods will exchange the functional group during the transposition, allowing rapid diversification of complex molecules. Preliminary data from the PI demonstrates this principle using vitamin B12 and Co(Salen) cocatalysts to achieve “remote elimination”, where primary alkyl electrophiles are translated into a 2-alkenes with terminal methyl group. We anticipate this approach will be general, allowing for transpositional C–X, C–N, C–O, and C–C bond-forming reactions (Project 2a). In parallel, the ability of vitamin B12 to enantioselectively convert meso-epoxides and aziridines to allylic alcohols and amines will be used to achieve enantioselective C–H functionalization of the epoxides and aziridines (Project 2b). Together, the proposed research will leverage the unique reactivity of HAT to deliver a suite of new catalytic reactions both making -and using- olefins to streamline the synthesis of molecules important to human health.

项目总结 氢原子转移(HAT)，即一个质子和一个电子同时运动，是一种 在综合方法论中日益重要的元素。在大自然广泛使用帽子的同时， 合成化学家们才刚刚开始使用去饱和酶和变位酶进行的过程。 以实现这种强大的、激进的转变的潜力。米拉提案描述了两个重要的新 国际和平研究所未来5年将探索的由HAT实现的领域：模数自由基氢化和 换位功能化。私家侦探准备通过他的导师在这一重要领域产生影响 职业生涯中，他设计了通过HAT运行的催化脱氢和脱氢甲酰化系统。这个 第一个研究领域涉及模块化、立体选择性加氢系统的开发，该系统能够 完全控制每个还原中心的组态和同位素组成(项目1)。初步 PI的工作表明，使用合作的氢原子可以实现自由基氢化 转移(CHAT)，其中每个氢原子从单独的催化剂到达，允许每个氢原子 催化剂可独立改性。这个项目的一个目标是独立地立体控制每个新的 通过使用两种不对称催化剂实现立体中心(项目1a)。这种设计将允许对映体选择性的反 还原，这是一种目前不可能实现的转变。同时独立的目标建立在初步数据的基础上 展示了每个催化剂从一个正交源获得氢原子，允许不同的同位素 可预见地在同一反应中交付(项目1b)。总而言之，该项目区将提供一种安装 从不饱和键开始的任何构型的H、D或T，在所有可能的同位素中进行选择 和立体同分异构体通过催化剂和试剂控制。第二个研究领域集中在发展上 新的芥子酶样反应，其中官能团以1，2-方式区域选择性地转置以重塑 分子结构(项目2)。然而，与变位酶不同的是，这些方法将交换 在转位过程中的官能团，允许复杂分子的快速多样化。初步数据 从PI演示了这一原理，使用维生素B12和Co(Salen)共催化剂来实现远程 消除“，其中伯烷基亲电体被转化为末端带有甲基的2-烯烃。我们 预计这种方法将是通用的，允许转置的C-X、C-N、C-O和C-C键的形成 反应(项目2a)。同时，维生素B12对映体选择性转化中环氧化物和 氮杂环丙烷到烯丙醇和胺将被用来实现对映体选择性的C-H官能化 环氧化物和氮杂环丙烷(项目2b)。总之，拟议的研究将利用HAT的独特反应性 提供一套制造和使用烯烃的新催化反应，以简化合成 对人类健康很重要的分子。

项目成果

Photochemical diazidation of alkenes enabled by ligand-to-metal charge transfer and radical ligand transfer.

• DOI: 10.1038/s41467-022-35560-3
• 发表时间: 2022-12-23
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Bian, Kang-Jie;Kao, Shih-Chieh;Nemoto, David, Jr.;Chen, Xiao-Wei;West, Julian G.
• 通讯作者: West, Julian G.

HAT Lessons Help Hydrogen Hop, Skip, and Jump.

• DOI: 10.1016/j.trechm.2022.09.001
• 发表时间: 2022-12
• 期刊: Trends in chemistry
• 影响因子: 15.7
• 作者: Buzsaki SR;Bian KJ;West JG
• 通讯作者: West JG

Photocatalytic, modular difunctionalization of alkenes enabled by ligand-to-metal charge transfer and radical ligand transfer.

• DOI: 10.1039/d3sc05231a
• 发表时间: 2023-12-20
• 期刊: CHEMICAL SCIENCE
• 影响因子: 8.4
• 作者: Bian, Kang-Jie;Nemoto Jr, David;Chen, Xiao-Wei;Kao, Shih-Chieh;Hooson, James;West, Julian G.
• 通讯作者: West, Julian G.

Publisher Correction: Photocatalytic hydrofluoroalkylation of alkenes with carboxylic acids.

出版商更正：烯烃与羧酸的光催化氢氟烷基化。

• DOI: 10.1038/s41557-023-01403-x
• 发表时间: 2023
• 期刊: Nature chemistry
• 影响因子: 21.8
• 作者: Bian,Kang-Jie;Lu,Yen-Chu;NemotoJr,David;Kao,Shih-Chieh;Chen,Xiaowei;West,JulianG
• 通讯作者: West,JulianG

RECENT ADVANCES IN BASE METAL-CATALYZED COOPERATIVE TRANSFER HYDROGENATION AND HYDRODEUTERATION OF ALKENES.

• DOI: 10.1016/j.tetlet.2023.154404
• 发表时间: 2023-02
• 期刊: Tetrahedron letters
• 影响因子: 1.8
• 作者: H. N. Tran;Julian G. West