Ligand discovery and optimisation for metal catalysed asymmetric synthesis

Identifying a suitable ligand is central to achieving high enantioselectivity in a metal catalysed reaction. The group has developed several new classes of ligand based principally on ferrocene and a related cobalt sandwich complex. These usually display planar and central chirality, and the basis of our approach to ligand optimisation involves controlling the selective formation of two or more of these chirality elements, and identifying the matched stereochemical relationship.

Representative ligands_2

Ferrocene-based ligands developed by several groups have been applied extensively in metal catalysed asymmetric synthesis, and many are available commercially from catalogue suppliers as summarised here. To aid the process of ligand identification, reaction summaries are provided for several of these ligand classes.


Metallacycles as catalysts and precatalysts in asymmetric synthesis

Metallacycles are typically bidentate ligand-metal complexes synthesised by C-H activation. Use of a ferrocene or cobalt sandwich complex precursor results in a new element of planar chirality, and the group has developed several stereoselective methods to control this reaction. Planar chiral metallacycles, notably palladacycles, have been widely used as catalysts in asymmetric synthesis. In addition they have the potential to be used as precatalysts following introduction of an additional ligating group (Y) and metal capture.



Sequential catalysis and the synthesis of bioactive compounds

The products of asymmetric catalysis may be further diversified by linking to a second catalysed process where orthogonal reactivity is exploited to give additional structural, functional group and stereochemical complexity. In this way simple prochiral  starting materials are converted quickly into novel fragment and lead-like compounds, starting points for the discovery of bioactive compounds.