Selective Oxidation of Primary C-H Bonds Using Late-Transition-Metal-Oxo Catalysts
使用后过渡金属氧合催化剂选择性氧化初级 C-H 键
基本信息
- 批准号:10555189
- 负责人:
- 金额:$ 6.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAlcoholsArchitectureAreaAttentionBindingCarbonChemicalsComplexCouplingDerivation procedureDevelopmentDisparityDrug IndustryElectronicsHealthHumanHydrogen BondingIn SituIndustryKineticsLigandsMedicineMetalsMethodologyMethodsNatural ProductsOrganic ChemistryOrganometallic CompoundsOxidantsOxygenPharmaceutical ChemistryPharmaceutical PreparationsPharmacologic SubstancePhysical condensationPreparationProductionReactionResearchRoleRouteSeriesSiteStructureStructure-Activity RelationshipSynthesis ChemistryTechnologyTransition Elementsanalogcarbenecatalystchemical propertychemical synthesiscomparativedrug discoveryelectronic structureforgingfunctional grouphydroxyl groupimprovedinnovationinsightmethyl groupnext generationnitrenenoveloxeneoxidationpreventscaffoldsmall moleculetooltrend
项目摘要
Project Summary/Abstract
Advances in organic synthetic methodology can profoundly impact the development of new and useful
medicines. For example, cross-coupling reactions have become indispensable tools in medicinal chemistry,
provided entry to previously inaccessible chemical space, and enhanced drug discovery efforts. Recently,
methods for the selective functionalization of C–H bonds have gained attention from the pharmaceutical industry
due to their potential utility in the diversification of drug-like scaffolds. Toward this end, metal-catalyzed C–H
functionalization reactions that take advantage of polar functional groups to direct site-selective C–H activation
have been extensively explored. In comparison, methods that avoid the use of pre-installed directing groups, or
“undirected” C–H functionalization reactions, are underdeveloped. Specifically, the selective and undirected
metal-catalyzed activation of strong primary C(sp3)–H bonds in the presence of weaker C–H bonds represents
an ongoing challenge in the field. Notably, such technologies would provide chemists with useful synthetic tools
to install functionality at remote sites on bioactive molecules. Though methods for the undirected selective
catalytic functionalization of methyl groups to forge C–C, C–B, and C–Cl bonds have recently emerged, a general
catalytic oxidation (C–O bond formation) of unactivated primary C(sp3)–H bonds is unknown.
Metal-stabilized carbenes, nitrenes, and oxenes are useful reactive intermediates that can insert carbon or
heteroatom functionality into strong C(sp3)–H bonds with ligand-controlled selectivities. Although early- and mid-
first-row transition-metal-oxo complexes have been intensively studied, first-row late-transition-metal-oxo
species (LTM-oxo) are less explored despite their potential utility for C–H oxidation. Indeed, synthesizing LTM-
oxo complexes represents a major challenge toward harnessing these highly reactive species as useful oxidants.
The proposed research aims to develop a modular route toward a series of LTM-oxo complexes bearing a novel
sterically-bulky triptycene-substituted dipyrrin ligand scaffold. This ligand architecture is expected to enforce
kinetic stability of the complexes to facilitate isolation and characterization efforts. The ligand scaffold will also
promote high-spin electronic configurations, which should weaken the M–O bond and render the complexes
more reactive toward C(sp3)–H oxidation. Finally, the reactivity of transiently-formed and sterically encumbered
LTM-oxo complexes will be harnessed to enable the selective and undirected catalytic oxidation of sterically
unhindered methyl groups. This methodology will also be applied toward the selective late-stage functionalization
of medicinally-relevant scaffolds. These efforts will result in the first general method for the catalytic undirected
oxidation of primary C(sp3)–H bonds. Moreover, these studies will provide the first unambiguous characterization
of high-spin LTM-oxo complexes and validate their synthetic utility for catalytic C–H oxidation.
项目摘要/摘要
有机合成方法学的进步可以深刻地影响新的和有用的开发
药物。例如,交叉偶联反应已经成为药物化学中不可或缺的工具,
提供了进入以前无法进入的化学空间的机会,并加强了药物发现工作。最近,
C-H键的选择性官能化方法受到制药行业的重视
由于它们在药物类支架的多样化方面具有潜在的实用价值。为此,金属催化的C-H
利用极性官能团引导C-H位选择性活化的官能化反应
已经得到了广泛的探索。相比之下,避免使用预安装的定向组的方法,或者
“非定向”的C-H官能化反应是不发达的。具体地说,选择性的和非定向的
在存在较弱的C-H键的情况下,金属催化的强的初级C(SP3)-H键的活化代表
这是这一领域正在进行的挑战。值得注意的是,这种技术将为化学家提供有用的合成工具。
在生物活性分子的远程位置安装功能。虽然针对非定向选择的方法
最近出现了甲基的催化官能化以形成C-C、C-B和C-Cl键
未活化的初级C(SP3)-H键的催化氧化(C-O键形成)未知。
金属稳定的卡宾、硝烯和恶烯是有用的活性中间体,可以插入碳或
杂原子官能团转变为具有配体控制选择性的强C(SP3)-H键。虽然早-中-
对第一排过渡金属氧合物进行了深入的研究,第一排后过渡金属氧合物
物种(LTM-oxo)尽管对C-H氧化具有潜在的效用,但被探索得较少。事实上,合成LTM-
氧代络合物是利用这些高活性物种作为有用的氧化剂的主要挑战。
这项拟议的研究旨在开发一种模块化路线,以获得一系列LTM-oxo络合物,该络合物具有一种新颖的
立体大体积的三三烯取代的联苯并吡喃配体支架。这一配体架构预计将强制
络合物的动力学稳定性有助于分离和表征工作。配体支架也将
促进高自旋电子构型,这应该会削弱M-O键并使络合物
对C(SP3)-H氧化反应更活跃。最后,暂态形成和空间受阻的反应性
LTM-oxo络合物将被利用来实现空间上的选择性和非定向催化氧化
不受阻碍的甲基。这种方法论也将适用于选择性后期功能化
与医学相关的支架。这些努力将导致第一个通用的催化不定向方法
初级C(SP3)-H键的氧化。此外,这些研究将提供第一个明确的描述
并验证了它们在催化C-H氧化反应中的合成效用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Timothy Bartlett Boit其他文献
Timothy Bartlett Boit的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Timothy Bartlett Boit', 18)}}的其他基金
Selective Oxidation of Primary C-H Bonds Using Late-Transition-Metal-Oxo Catalysts
使用后过渡金属氧合催化剂选择性氧化初级 C-H 键
- 批准号:
10387337 - 财政年份:2022
- 资助金额:
$ 6.91万 - 项目类别:
相似海外基金
Collaborative Research: Overlooked Oxidation of Aqueous Alcohols: Kinetics, Mechanism, and Relevance to Water Reuse
合作研究:被忽视的水醇氧化:动力学、机制以及与水回用的相关性
- 批准号:
2304861 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Continuing Grant
STTR Phase I: Development of Modular Reactors to Convert Methane to Alcohols at Low Temperatures
STTR 第一阶段:开发在低温下将甲烷转化为醇的模块化反应器
- 批准号:
2151256 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Standard Grant
Development of amine-dehydrogenase and lyase biocatalysts for the sustainable manufacturing of unnatural chiral amino acids and amino alcohols
开发胺脱氢酶和裂解酶生物催化剂,用于可持续生产非天然手性氨基酸和氨基醇
- 批准号:
2870226 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Studentship
Collaborative Research: Overlooked Oxidation of Aqueous Alcohols: Kinetics, Mechanism, and Relevance to Water Reuse
合作研究:被忽视的水醇氧化:动力学、机制以及与水回用的相关性
- 批准号:
2304860 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Continuing Grant
Postdoctoral Fellowship: MPS-Ascend: Development of Selective Reaction Schemes for Photoactivation of Alcohols
博士后奖学金:MPS-Ascend:醇光活化选择性反应方案的开发
- 批准号:
2316541 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Fellowship Award
Development of phosphorylation of alcohols in protein based on the structural modification of phosphoenolpyruvate
基于磷酸烯醇丙酮酸结构修饰的蛋白质醇磷酸化研究进展
- 批准号:
22KJ1152 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Nickel Cross-Coupling Cascades with α-Heteroatom Radicals to Prepare Sterically Hindered Alcohols and Amines
镍与α-杂原子自由基交叉偶联级联制备位阻醇和胺
- 批准号:
10604535 - 财政年份:2023
- 资助金额:
$ 6.91万 - 项目类别:
Towards a better understanding of the effect of the pentafluorosulfanyl group on the lipophilicity and acid/base properties of alcohols and amines
更好地了解五氟硫基对醇和胺的亲脂性和酸/碱性质的影响
- 批准号:
571856-2021 - 财政年份:2022
- 资助金额:
$ 6.91万 - 项目类别:
Alliance Grants
Pd-Catalyzed C(sp3)-H Functionalizations Directed by Free Alcohols and Boc-Protected Amines
由游离醇和 Boc 保护的胺引导的 Pd 催化 C(sp3)-H 官能化
- 批准号:
10606508 - 财政年份:2022
- 资助金额:
$ 6.91万 - 项目类别:
Facile One-Pot Reductive Deoxygenations of Alcohols and Carboxylic Acids Using Sulfuryl Fluoride
使用硫酰氟轻松进行醇和羧酸的一锅还原脱氧
- 批准号:
546996-2020 - 财政年份:2022
- 资助金额:
$ 6.91万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral