Studies of Intermolecular Asymmetric Halofunctionalisations of Alkenes

烯烃卤代官能化，即亲电卤素和亲核试剂在双键上的加成，是有机化学中基本的碳-杂原子键形成反应。这些反应有利于前手性烯烃部分转化成两个新的立体碳中心，具有可预测的区域控制和非对映选择性，因此是有吸引力的路线走向不同的对映体纯，杂原子轴承邻位二取代化合物。然而，尽管烯烃卤代官能化的立体化学过程在过去的世纪中已经得到了很好的建立，但是开发这些反应的催化、不对称变体对现代合成界提出了重大挑战。在过去的十年中，出现了几个对映体选择性分子内卤代官能化（涉及通过共价连接的亲核试剂捕获卤离子）的例子，其中许多利用手性双生物碱或BINOL-磷酸作为有机催化剂。相比之下，使用这些有机催化剂中的任一种的成功的对映选择性分子间卤代官能化反应（利用与起始烯烃无关的亲核试剂）的实例非常少。这是因为相对于它们的分子内对应物，对分子间系统的机械理解通常较差。受Li等人结果的启发，本研究计划旨在阐明有机催化分子间卤代官能化的机理，并在不同的有机催化体系之间进行比较。这将涉及使用析因设计的彻底优化实验，用于分析动力学数据的化学计量学，所有这些都与计算方法相结合，以围绕我们的实验数据开发理论。

Description of the chemistry and potentially issues in the fieldAlkene halofunctionalisations, namely the addition of an electrophilic halogen and a nucleophile across a double bond, are fundamental carbon-heteroatom bond-forming reactions in organic chemistry. These reactions facilitate the conversion of a prochiral alkene moiety into two new stereogenic carbon centres with predictable regiocontrol and diastereoselectivity, and are therefore attractive routes towards a diverse array of enantiopure, heteroatom-bearing vicinal disubstituted compounds. However, although the stereochemical course of alkene halofunctionalisations has been well-established over the past century, developing catalytic, asymmetric variants of these reactions has presented a significant challenge for the modern synthetic community. In the last decade, several examples of enantioselective intramolecular halofunctionalisation (involving capture of a halonium ion by a covalently tethered nucleophile) have emerged, many of which utilise chiral bisalkaloids or BINOL-phosphoric acids as organocatalysts. In contrast, there are very few examples of successful enantioselective intermolecular halofunctionalisation reactions (utilising a nucleophile extraneous to the starting alkene) using either of these organocatalysts. This is because of a generally poor mechanistic understanding of the intermolecular systems relative to their intramolecular counterparts. Inspired by results of Li et al., this project intends to elucidate the mechanisms of organocatalytic intermolecular halofunctionalisation, with comparisons being made between different organocatalytic systems. This will involve thorough optimisation experiments using factorial designs, chemometrics for the analysis of kinetic data, all tied in with a computational approach to develop theories surrounding our experimental data.