New Insights, New Catalysts and New Processes using Enantioselective Carbonylations.

使用对映选择性羰基化的新见解、新催化剂和新工艺。

• 批准号: EP/M003868/1
• 负责人: Matthew Clarke
• 金额: $ 66.33万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM003868%2F1
• 关键词: New; Insights; Catalysts; Processes; using

This project is in the field of chemo-catalysis. Catalysis is used somewhere in the manufacture of most everyday items (plastics, drugs, food supplements, flavours/fragrances, finishes and coatings). Amongst the most important reactions, generally used in the manufacture of diverse products such as varnishes, plastics, banana flavouring and anti-inflammatories!, are those that use carbon monoxide as a building block. Carbon monoxide is one of the cheapest chemicals and can come from coal, oil, gas and renewables. Due to the low price of carbon monoxide and the fact that it can, in the presence of a catalyst, react in a very clean fashion with other molecules, these catalytic carbonylation reactions generate very little waste and are economical even at very large scale (Millions of tonnes). These features also potentially make this type of reaction a clean and economical way to make much higher value, more sophisticated molecules such as drugs. However, to make these molecules, exquisite control of several types of selectivity is needed. For example, many drugs exist as two mirror image forms (optical isomers) and one isomer must be made prefentially. The other optical isomer is often inactive, or in fact can cause an alternative biological effect (The side effects of Thalidomide are a tragic example of one optical isomer causing unwanted biological effects). This has led to a massive research effort by chemists to develop chemical reactions that are capable of selectively producing a single optical isomer ('Asymmetric Synthesis'). Significant developments have been made in this area, with several Nobel prizes in chemistry being awarded to some of the pioneers in asymmetric synthesis. The investigators group has recently obtained exciting preliminary results developing catalysts that can control several aspects of selectivity in model studies on a few types of carbonylation, including excellent selectivity to one optical isomer. This new project addresses building on these results to develop routes to different target chemicals.Development of new types of carbonylation or the ability to work on hitherto unreactive substrates is needed for the higher value fine chemicals/pharma intermediates sector. A number of potentially exciting new reactions such as combining several reaction into one stage of a synthesis, and one reactor, one set of solvents, purification etc. are proposed. This project will also gain mechanistic insights on the new catalyst and use this information to generate refined catalyst design and rational design of catalysts to accomplish new tasks. Overall the project has the potential to impact on fundamental knowledge, generate proof of concept for new industrial targets, and provide better, more benign routes to a range of important chemicals.

这个项目是在化学催化领域。催化在大多数日常用品(塑料、药品、食品补充剂、香料/香料、涂饰剂和涂料)的生产中都有应用。在最重要的反应中，通常用于制造各种产品，如清漆、塑料、香蕉调味料和消炎剂！其中最重要的反应是使用一氧化碳作为积木。一氧化碳是最便宜的化学品之一，可以来自煤炭、石油、天然气和可再生能源。由于一氧化碳价格低廉，而且在催化剂存在的情况下，它可以与其他分子以非常清洁的方式反应，这些催化羰化反应产生的废物非常少，即使在非常大的规模(数百万吨)下也是经济的。这些特点也可能使这种类型的反应成为一种清洁和经济的方式，以制造更高价值、更复杂的分子，如药物。然而，为了制造这些分子，需要对几种类型的选择性进行精细的控制。例如，许多药物以两种镜像形式(光学异构体)存在，必须优先制造一种异构体。另一种光学异构体通常是不活跃的，或者实际上可以引起另一种生物效应(沙利度胺的副作用是一个光学异构体引起不想要的生物效应的悲惨例子)。这导致化学家们进行了大量的研究工作，以开发能够选择性地产生单一光学异构体的化学反应(不对称合成)。在这一领域已经取得了重大进展，一些不对称合成的先驱被授予了几个诺贝尔化学奖。研究小组最近在开发催化剂方面取得了令人振奋的初步结果，这些催化剂可以在几种类型的羰化反应的模型研究中控制几个方面的选择性，包括对一个光学异构体的优异选择性。这一新项目致力于在这些结果的基础上开发不同目标化学物质的路线。对于价值较高的精细化学品/制药中间体部门，需要开发新型的羰化反应或在迄今未反应的底物上工作的能力。提出了一些潜在的令人兴奋的新反应，如将几个反应合并为一个合成步骤，以及一个反应器，一组溶剂，纯化等。该项目还将获得对新催化剂的机械见解，并利用这些信息来产生改进的催化剂设计和合理的催化剂设计，以完成新的任务。总体而言，该项目有可能影响基础知识，为新的工业目标提供概念证明，并为一系列重要化学品提供更好、更良性的途径。

项目成果

Phospholane-Phosphite Ligands for Rh Catalyzed Enantioselective Conjugate Addition: Unusually Reactive Catalysts for Challenging Couplings

• DOI: 10.1002/ejoc.202000336
• 发表时间: 2020-05
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Sophie H. Gilbert;J. Fuentes;D. Cordes;A. Slawin;M. Clarke

Diastereoselective and Branched-Aldehyde-Selective Tandem Hydroformylation-Hemiaminal Formation: Synthesis of Functionalized Piperidines and Amino Alcohols.

• DOI: 10.1021/acs.orglett.7b01049
• 发表时间: 2017-05
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Rachael Pittaway;J. Fuentes;M. Clarke

A Highly Enantioselective Alkene Methoxycarbonylation Enables a Concise Synthesis of ( S )-Flurbiprofen

高度对映选择性烯烃甲氧基羰基化可实现 (S)-氟比洛芬的简洁合成

• DOI: 10.1002/ejoc.201700791
• 发表时间: 2017
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Harkness G

Understanding a Hydroformylation Catalyst that Produces Branched Aldehydes from Alkyl Alkenes

• DOI: 10.1021/jacs.7b09164
• 发表时间: 2017-11-08
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Dingwall, Paul;Fuentes, Jose A.;Clarke, Matthew L.
• 通讯作者: Clarke, Matthew L.

Rapid Asymmetric Transfer Hydroformylation (ATHF) of Disubstituted Alkenes Using Paraformaldehyde as a Syngas Surrogate.

• DOI: 10.1002/chem.201502049
• 发表时间: 2015-07-20
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Fuentes JA;Pittaway R;Clarke ML
• 通讯作者: Clarke ML