Organic Synthesis
Cross-coupling reactions
Synthesis of bioactive compounds

The Suzuki reaction is a simple and very popular method for the construction of carbon-carbon bonds, especially between aromatic substrates. Catalysts for this transformation should ideally be used in very low loadings and be applicable to a wide range of substrates, including aryl chlorides. Our solution to these demands is the ferrocene based palladacycle 2, synthesised within minutes by addition of palladium acetate to ligand 1. Addition of as little as 0.01mol% of 2 to the Suzuki reaction of para-chlorotoluene results in a clean reaction at 60 °C, a reaction that may also be carried out at room temperature by use of 1 mol% of 2.1 Accumulating evidence points to a palladacycle of this type acting as a precatalyst, requiring in situ transformation into a Pd(0) species for entry into the catalytic manifold. The details of this process are currently under investigation.

In our earlier work we focused on ferrocene equivalent of tris(ortho-tolylphosphine) 3 which we reasoned would have superior steric and electronic properties over this widely employed ligand. The synthesis employed enantiopure bromoferrocene 4 (from a ferrocenyloxazoline) which was readily converted into the C3-symmetric 5 (TomPhos). On combination with Pd2(dba)3 the resulting catalyst successfully transformed a range of aryl chloride starting materials into cross-coupled products.2

X-ray crystal structure of TomPhos 4
[1] F. X. Roca and C. J. Richards, Chem. Commun., 2003, 3003. [2] T. E. Picket, F. X. Roca and C. J. Richards, J. Org. Chem., 2003, 68, 2592