Oxazaborolidinium Ion Catalysed Asymmetric Diels-Alder Reactions of Anthracene Derivatives

自然界中的许多分子以两种不同的形式存在，它们具有相同的原子和键的连通性，但原子和基团在空间上的排列不同。这些不同的形式被称为对映体，在现代合成有机化学中，很多努力都致力于开发有效的途径，以促进一种对映体的选择性制备。解决这一问题的较成熟的方法之一是将手性助剂附着在选定的底物上，其功能是控制给定过程的选择性，随后去除和回收助剂。我们以前开发了一种有效的方法，采用了一种替代的辅助方法，使用手性取代蒽的不对称Diels-Alder环加成反应。这种方法对于许多烯烃底物来说是非常成功的，我们已经开发出几种天然产物的高效化学合成方法。本项目旨在通过开发第一个催化不对称Diels-Alder环加成蒽及其衍生物，大大扩大这一过程的范围和适用性。我们的目标是进行一系列优化，以映射适当的蒽和烯烃底物的反应性和选择性。一旦这已经完成，我们将进行所得产品的不对称转化，特别是看格氏加成和烯醇醇烷基化。然后将开发的化学物质应用于制备两种结构相关的天然产物目标，以展示整个过程的效率。与这里描述的工作平行，我们也将致力于开发基于顺-2-氨基-吲哚-1-醇的替代催化剂体系，这是一种我们有相当经验的催化剂前体。

Many molecules in Nature exist in two different forms which have the same connectivity of atoms and bonds, but differ in their arrangement of atoms and groups in space. These different forms are termed enantiomers and much effort in modern synthetic organic chemistry as been devoted to developing efficient routes that facilitate the selective preparation of one enantiomer over another. One of the more established ways to address this problem is to attach a chiral auxiliary to the substrate of choice, the function of which is to control the selectivity of a given process, followed by subsequent removal and recovery of the auxiliary. We have previously developed efficient methodology that employs an alternative auxiliary approach using an asymmetric Diels-Alder cycloaddition reaction of chiral substituted anthracenes. This methodology has been very successful for a number of alkene substrates and we have developed efficient chemical syntheses of several classes of natural products. This project aims to considerably widen the scope and applicability of this process by developing the first catalytic asymmetric Diels-Alder cycloaddition of anthracene and its derivatives. We aim to conduct a series of optimisations to map the reactivity and selectivity of appropriate anthracene and alkene substrates. Once this has been performed we will conduct asymmetric transformations of the products obtained, in particular looking at Grignard additions and enolate alkylation. The chemistry developed will then be applied to the preparation of two structurally related natural product targets to showcase the efficiency of the overall procedure. In parallel to the work described here, we will also aim to develop alternative catalyst systems based up cis-2-amino-indan-1-ol, a catalyst precursor for which we have considerable experience.