Copper and rhodium catalyzed dynamic kinetic asymmetric transformations

铜和铑催化的动态动力学不对称转变

• 批准号: EP/N022246/1
• 负责人: Stephen Fletcher
• 金额: $ 42.41万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN022246%2F1
• 关键词: Copper; rhodium; catalyzed; dynamic; kinetic

The development of catalytic methods for asymmetric synthesis is one of the foremost achievements in chemistry. Asymmetric catalysis is a key technology in the efficient development of new medicines, fragrances, polymers, materials and catalysts. While many broadly useful methods for catalytic asymmetric oxidation and reduction exist, there are far fewer asymmetric methods for forming carbon-carbon bonds, which make up the framework of organic molecules. Typically in asymmetric catalysis, prochiral (usually flat) starting materials are used and the catalyst selects one side of the starting material for a reaction that introduces chirality and selectively produces one enantiomer of product. Where an 'enantiomer' is a specific 3d orientation, often described as one "hand" where there are two possible hands, and the hands or enantiomers are non-superimposible mirror images of each other. This project aims to develop new asymmetric reactions where racemic starting material (a 50:50 mixture of two enantiomers, or 'hands') is converted selectively into one enantiomer of a product at the same time that a new carbon-carbon bond forms. This is a much less straightforward process than using prochiral starting materials and there are only very few types of reaction that can use this strategy. However, as there are many more racemic than prochiral molecules, methods that use racemic starting materials would be very useful in asymmetric synthesis. Catalytic asymmetric carbon-carbon bond forming methods that use racemic starting materials are known, but these are limited to the combination of a precious metal catalyst (palladium, iridium, etc.) and an especially stabilized reaction partner. Here we will develop new methods that don't require stabilized reaction partners. We will use nuclear magnetic resonance spectroscopy to study the new reactions and try to understand the chemical pathways that are occurring. We expect that the information from the spectroscopic studies will be very useful in designing additional reactions. Overall, these studies will provide important new ways to rapidly synthesize a wide range of molecules with a wide variety of uses.

不对称合成催化方法的发展是化学领域最重要的成就之一。不对称催化是高效开发新药、香料、聚合物、材料和催化剂的关键技术。虽然存在许多用于催化不对称氧化和还原的广泛有用的方法，但用于形成构成有机分子框架的碳-碳键的不对称方法要少得多。通常在不对称催化中，使用前手性（通常平坦的）起始材料，并且催化剂选择起始材料的一侧用于引入手性并选择性地产生产物的一种对映异构体的反应。其中"对映异构体“是特定的3d取向，通常被描述为一个“手”，其中存在两个可能的手，并且手或对映异构体是彼此不可重叠的镜像。该项目旨在开发新的不对称反应，其中外消旋起始材料（两种对映体的50：50混合物，或“手”）选择性地转化为产物的一种对映体，同时形成新的碳-碳键。与使用前手性起始材料相比，这是一个不那么直接的过程，并且只有很少类型的反应可以使用这种策略。然而，由于存在比前手性分子多得多的外消旋分子，因此使用外消旋起始材料的方法在不对称合成中将是非常有用的。使用外消旋起始材料的催化不对称碳-碳键形成方法是已知的，但这些方法限于贵金属催化剂（钯、铱等）与催化剂的组合。和特别稳定的反应组分。在这里，我们将开发新的方法，不需要稳定的反应伴侣。我们将使用核磁共振光谱来研究新的反应，并试图了解正在发生的化学途径。我们期望从光谱研究中得到的信息在设计其他反应中将是非常有用的。总的来说，这些研究将提供重要的新方法来快速合成具有广泛用途的各种分子。

项目成果

Enantiomerically Enriched Tetrahydropyridine Allyl Chlorides

对映体富集的四氢吡啶烯丙基氯

• DOI: 10.26434/chemrxiv.8181686
• 发表时间: 2019
• 作者: Fletcher S

Cp2ZrMeCl: A Reagent for Asymmetric Methyl Addition.

• DOI: 10.1021/acs.orglett.6b01829
• 发表时间: 2016-07
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Kilian Garrec;S. Fletcher

Enantio- and Diastereoselective Suzuki-Miyaura Coupling with Racemic Bicycles

对映体和非对映选择性 Suzuki-Miyaura 与外消旋自行车的偶联

• DOI: 10.1002/ange.201906478
• 发表时间: 2019
• 期刊: Angewandte Chemie
• 作者: Goetzke F

Highly Enantioselective Hiyama Cross-Coupling via Rh-Catalyzed Allylic Arylation of Racemic Allyl Chlorides

通过 Rh 催化外消旋烯丙基氯的烯丙基芳基化实现高度对映选择性 Hiyama 交叉偶联

• DOI: 10.26434/chemrxiv.6960404
• 发表时间: 2018
• 作者: Fletcher S

Catalytic asymmetric hydrometallation of cyclobutenes with salicylaldehydes.

• DOI: 10.1039/d1sc06035j
• 发表时间: 2021-12-22
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Goetzke FW;Sidera M;Fletcher SP
• 通讯作者: Fletcher SP