New chiral isonitrile iron catalyst for the asymmetric transfer hydrogenation of ketones

Asymmetric catalysis is in principle the most efficient strategy for the synthesis of enantiopure compounds, and the enantioselective reduction of double bonds is one of its most well-developed applications. However, most known enantioselective catalysts rely on very expensive and toxic precious metals (e.g., Ru, Rh, Ir, Pd), which may prevent in some cases their implementation on a large scale. Therefore, replacing precious metals with cheap first-row transition metals would be a major breakthrough, disclosing new methodologies of enormous industrial impact. The Fe-based methodologies are of particular industrial interest due to the ready availability (4.7 wt% of the crust of earth) and scarce toxicity of Fe.[1] In spite of these attracting features, to date the catalytic applications of Fe in enantioselective reductions are still very limited:[2] a few catalysts have been developed for ketones[3] and ketoimines,[4] while no examples were reported with olefins. In the effort to create new chiral Fe-catalysts for the enantioselective reduction of ketones, our attention was captured by the isonitrile ligands, due to their ability to stabilize Fe(II) and to behave as “non-innocent ligands” in transfer hydrogenation processes proceeding through a Meerwein-Ponndorf-Verley-like mechanism.[5] We thus designed and synthesized the two BINOL-derived ligand families A and B (Fig. 1), differing for the length of the ‘arms’ bearing the isonitrile groups. The corresponding complexes Fe(L)2Cl2 were synthesized, isolated and tested in the transfer hydrogenation of acetophenone in the presence of iPrOH. A low but encouraging 20%e.e. was obtained in the presence of complex Fe(B2)2Cl2, featuring OMe substituents at the 3,3’-positions of the binaphthyl moiety. We are currently synthesizing new ligands with bulkier substituents in the 3,3’-positions, with the aim to increase the enantiomeric excess. This work was funded by the European Commission [EID-ITN Network ‘REDUCTO’, contract n. PITN-GA-2012-316371].