Cyclizations and cyclization cascades triggered by new reductions

合成化学-分子水平的构建-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着至关重要的作用，他们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，科学的进步将放缓，社会的利益可能会失去。合成化学的学科是建立在对原材料中存在的“官能团”的操作上的。羰基，其中一个碳原子与氧双键结合，可以说是这些官能团中最重要的，并且该基团的反应形成了该学科的基石。例如，将羰基化合物还原为醇是工业中的关键过程。以全新的方式操纵羰基的方法有可能对全球学术界和工业界产生重大影响。我们最近发现，羧酸衍生物中的羰基可以利用用户友好的商业试剂SmI 2提供的电子进行还原。至关重要的是，该试剂只有在与活化添加剂混合时才能进行还原。传统上，这种“电子转移”还原需要还原剂，如Na，Li和K，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。我们新的还原工作原理是将电子从金属钐（Sm）泵入羧酸衍生物的羰基。这个过程产生了被称为自由基的反应性物质，这些物质可用于形成碳-碳键。在这个项目中，我们将使用在新的成环反应（“环化”）中的新还原中产生的自由基。此外，我们将使用产生的自由基来触发我们称之为“环化级联”的事件链，这些事件在单一操作中将简单的起始材料转化为复杂的多环产物，使用单一试剂，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反应来快速构建著名抗癌药物Taxol.In第二阶段的项目，我们计划使用“手性”添加剂来激活商业SmI 2试剂的复杂分子框架，从而展示新工艺的价值。“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SmI 2手性添加剂的单手形式，我们计划采用简单，对称的起始材料（由廉价和可再生的化学原料丙二酸制成），并使用新的环化反应将其选择性地转化为复杂，不对称，高价值的产品。使用手性配体控制电子转移极具挑战性，我们的研究将对世界各地的合成实验室产生重大影响。

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.