Versatile Chiral Building Blocks by Catalytic C-H and C-C Activation

轴向手性联芳化合物在不对称反应中被广泛用作辅助配体，具有很高的对映体选择性，是许多生物活性天然产物的一部分。虽然轴向手性联芳基化合物是一个很有吸引力的合成目标，但它们很难制备。现有方法的主要局限性之一是底物范围有限，因此需要一种更通用的方法来合成轴向手性联芳基。为了开发这种方法，本项目将探索两种涉及催化C-C和C-H活化的方法。特别是，通过联苯中的应变C-C键(图1，方案A)和邻位C-H键(图2，方案B)的C-C官能化，将获得一系列官能化的联芳基。为了开发C-C功能化方法，将首先在模型反应中测试一系列具有各种配体的钯、镍、铑和铱金属前体，以确定最佳催化体系。然后将通过试验联苯与一系列硼烷、二硼烷和硅硼烷的官能化来探索这一方法的范围。硼基或硅基取代的联芳基特别令人感兴趣，因为它们易于随后的官能化，因此它们有可能获得更广泛的底物范围。此外，具有各种R-取代基的联苯将在反应中进行测试，看看电子和立体结构对开环有什么影响。在第二种C-H活化方法中，将使用定向基团通过过渡金属催化剂在邻位位置添加官能团(图1，方案B)。要探索的官能团包括硼基、硅基、炔基和氨基，类似地，因为它们易于随后的官能化。在这两种方法中，手性金属催化剂和非手性金属催化剂在手性添加剂的存在下都可以实现手性诱导。

Axially chiral biaryl compounds are of high importance as they are widely used as auxiliary ligands in asymmetric reactions giving high enantioselectivities and form a part of many biologically active natural products. Although axially chiral biaryl compounds are an attractive synthetic target, they are difficult to make. One of the main limitations to existing methods is a limited substrate scope, thus a more general method for the synthesis of axially chiral biaryls is needed. To develop such a method, two approaches that involve catalytic C-C and C-H activation will be explored in this project. In particular, a range of functionalised biaryls will be obtained by C-C functionalisation of strained C-C bonds in biphenylenes (Fig. 1, Scheme A) and ortho C-H bonds in biphenyls (Fig. 2, Scheme B). To develop the C-C functionalisation approach, a range of palladium, nickel, rhodium and iridium metal precursors with a variety of ligands will be initially tested in a model reaction to identify the best catalytic system. The scope of this approach will then be explored by trialling functionalisation of the biphenylenes with a range of boranes, diboranes and silaboranes. Boryl or silyl substituted biaryls are of particular interest because they are amenable to subsequent functionalisation, thus they have the potential to give access to a wide substrate scope. In addition, biphenylenes with a variety of R-substituents will be tested in the reaction to see what effect electronics and sterics have on the ring opening. In the second approach C-H activation, a directing group will be used to add functionality in the ortho position using a transition metal catalyst (Fig 1. Scheme B). The functional groups to be explored include boryl, silyl, alkynyl, and amino, similarly because they are amenable to subsequent functionalisation. Chirality induction in both approaches will be achieved by the use of chiral metal catalysts and achiral metal catalysts in the presence of chiral additives.