Synthesis of enolates by nucleophilic substitution

我们需要能够制造新的分子，以继续推动社会可用的技术。在一系列令人兴奋的应用中，新化合物的合成为新药物、塑料、显示器材料和太阳能电池的发现奠定了基础。我们需要能够以一种尽可能高效的方式制造这些分子，并将我们对环境的影响降至最低。对合成效率极其重要的一个因素是选择性。反应必须尽可能地具有选择性，这样它才能产生我们想要的化合物。非选择性反应会产生不需要的副产物，必须去除这些副产物。这会产生必须去除的废物，通常需要耗时的程序，而且必须以最大限度地减少对环境的影响的方式处理。在合成中特别有用的一类化合物是酮。这些化合物表现出非常多功能的反应性，并能够形成各种新的键。酮的一种关键反应方式是以一种被称为烯醇的中间体的形式。烯醇酸盐是我们形成新的碳-碳键的关键中间体之一，它构成了所有有机分子的框架。醇化物通常是通过使用碱去除附着在直接与羰基相邻的碳上的氢离子来制造的。这就留下了一种带负电荷的中间体，它可以与亲电性(带正电的物种)反应，这种制造烯醇的经典方法在选择性上会带来几个挑战。主要的一点是，酮在其羰基的两边都可能有氢原子，这些氢原子中的任何一个都可以被碱除去。这会导致形成混合的烯醇化合物，最终产品的产量将会降低。我们的制造烯醇化合物的策略通过以一种新的方式制造烯醇化合物来绕过这一挑战。我们不是通过去除氢离子来制造烯醇化合物，而是通过取代酯来生成我们的烯醇中间体。为了做到这一点，我们将酯与含有原子(硼)的亲核剂反应，使其行为像带负电荷一样。这就有选择地控制了烯醇基中的部分负电荷的位置，因为只有引入了含硼基团的羰基一侧才能进一步反应。这避免了选择性问题，并意味着我们可以比以前更有效和更高产量地生产一系列高价值的酮。本项目旨在充分探索这种新的选择性酮合成，以了解我们可以用这种方法制造的体系的类型。

We need to be able to make new molecules to continue to advance technology that is available to society. The synthesis of new compounds underpins the discovery of new drugs, plastics, materials for displays and solar cells amongst a huge range of exciting applications. We need to be able to make these molecules in a way that is efficient as possible and minimises our impact on the environment. One factor that is extremely important for the efficiency of a synthesis is selectivity. A reaction must be as selective as possible so that it only generates our desired compound. A non-selective reaction will generate unwanted side-products that must be removed. This generates waste that must be removed, often using time-consuming procedures, and also must be disposed of in a way that minimises impact on the environment.One class of chemical compound that are especially useful in synthesis are ketones. These compounds show very versatile reactivity and are able to form a diverse range of new bonds. One key way that ketones react is as a type of intermediate known as an enolate. Enolates are one of our key intermediates for forming new carbon-carbon bonds, which make up the framework of all organic molecules. Enolates are normally made by removing a hydrogen ion attached to a carbon directly adjacent to a carbonyl group using a base. This leaves behind a negatively-charged intermediate which can react with an electrophile (positively charged species)This classical method for making an enolate can present several challenges with selectivity. The main one is that a ketone may have hydrogen atoms on either side of its carbonyl group, and either of these may be removed by a base. This leads to a mixture of enolates being formed and the final product will have a reduced yield as a result.Our strategy for making enolates circumvents this challenge by making enolates in a new way. Instead of making enolates by removing a hydrogen ion, we generate our enolate intermediate by substitution of an ester. To do this we react the ester with a nucleophile containing an atom (boron) that will make it act as if it is negatively charged. This then controls the site of partial negative charge in the enolate selectively, as only the side of the carbonyl group where the boron-containing group was introduced can react further. This prevents issues with selectivity and means that we can make a range of highly valuable ketones more efficiently and higher yielding than we could previously. This project aims to explore this new selective ketone synthesis fully to understand the types of systems that we can make using this method.