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

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.