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Cyclizations and cyclization cascades triggered by new reductions

新还原引发的环化和环化级联

基本信息

批准号：
EP/L00125X/1
负责人：
David Procter
金额：
$ 37.09万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FL00125X%2F1
关键词：
Cyclizations cyclization cascades triggered new

项目摘要

Synthetic chemistry - construction at the molecular level - continues to make a major impact on global society through its crucial role in the work of millions of industrial and academic scientists who require new molecules and materials for their studies: if new molecules and materials can't be made, the advancement of science will slow and benefits for society may be lost. The discipline of synthetic chemistry is built on the manipulation of 'functional groups' that are present in starting materials. The carbonyl group, in which a carbon atom is doubly-bonded to oxygen, is arguably the most important of these functional groups and the reactions of this group form the bedrock of the discipline. For example, the reduction of carbonyl compounds to alcohols is a key process in industry. Methods that allow carbonyl groups to be manipulated in a fundamentally new way have the potential to make a major impact on the global scientific community in academia and industry.We have recently found that the carbonyl groups in carboxylic acid derivatives can be reduced using electrons supplied by the user-friendly, commercial reagent, SmI2. Crucially, the reagent can only carry out the reductions when it is mixed with activating additives. Traditionally, these kind of 'electron transfer' reductions required reducing agents such as Na, Li and K that ignite on contact with moisture. Our new discovery therefore provides an attractive, safer alternative reagent system for important chemical processes. Our new reduction works by pumping electrons from the metal - samarium (Sm) - into the carbonyl groups of carboxylic acid derivatives. The process results in reactive species called radicals and these species can be used to form carbon-carbon bonds. In this project we will use the radicals generated in our new reductions in new ring-forming reactions ('cyclizations'). Furthermore, we will use the radicals generated to trigger a chain of events we call 'cyclization cascades' that convert simple starting materials to complex polycyclic products in a single operation, using a single reagent, with control of the shape, or stereochemistry, of the molecule under construction. We will show the value of the new processes by using a cascade cyclization to rapidly build the complex molecular framework of the famous anticancer drug, Taxol.In the second phase of the project, we plan to activate the commercial SmI2 reagent using a 'chiral' additive. 'Chiral' compounds can exist in two forms - think of your left and right hand. Using a single-handed form of the chiral additive with SmI2, we plan to take simple, symmetrical starting materials (made from the inexpensive and renewable chemical feedstock, malonic acid) and convert them selectively into complex, unsymmetrical, high-value products using the new cyclization reactions. Using chiral ligands to control electron transfer is extremely challenging and our studies will make a major impact in synthesis laboratories around the world.

合成化学-在分子水平上的构建-继续对全球社会产生重大影响，因为它在数百万工业和学术科学家的工作中发挥了关键作用，这些科学家需要新的分子和材料进行研究：如果不能制造新的分子和材料，科学的进步将会放缓，对社会的好处可能会丧失。合成化学的学科建立在对原料中存在的“官能团”的操纵上。其中一个碳原子与氧双键的羰基可以说是这些官能团中最重要的，而这个官能团的反应构成了这门学科的基础。例如，将羰基化合物还原为醇是工业中的一个关键过程。允许以一种全新的方式操纵羰基的方法有可能对学术界和工业界的全球科学界产生重大影响。我们最近发现，可以使用用户友好的商业试剂SmI2提供的电子来还原羧酸衍生物中的羰基。关键是，试剂只有在与活性添加剂混合时才能进行还原。传统上，这种“电子转移”还原需要Na、Li和K等还原剂，它们在与水分接触时会点燃。因此，我们的新发现为重要的化学过程提供了一种有吸引力的、更安全的替代试剂系统。我们的新还原工作原理是将电子从金属--Sm(Sm)--泵入羧酸衍生物的羰基中。这个过程产生了被称为自由基的活性物种，这些物种可以用来形成碳-碳键。在这个项目中，我们将在新的成环反应(环化反应)中使用在我们的新还原反应中产生的自由基。此外，我们将使用产生的自由基来触发一系列我们称为环化级联的事件，在一次操作中将简单的起始材料转化为复杂的多环产品，使用单一试剂，并控制正在构建的分子的形状或立体化学。我们将通过使用级联环化来快速构建著名抗癌药物紫杉醇的复杂分子框架来展示新工艺的价值。在项目的第二阶段，我们计划使用手性添加剂激活商业SmI2试剂。手性化合物可以以两种形式存在--想想你的左手和右手。使用单手形式的SmI2手性添加剂，我们计划获得简单、对称的起始原料(由廉价的可再生化学原料丙二酸制成)，并通过新的环化反应选择性地将它们转化为复杂的、不对称的、高价值的产品。使用手性配体来控制电子转移是非常具有挑战性的，我们的研究将在世界各地的合成实验室产生重大影响。