Iron-catalysed hydrogenation and hydroboration reactions
MacNair, Alistair James
Hydrogenation and hydrofunctionalisation reactions provide efficient, sustainable methodologies for the manipulation of synthetic handles and the formation of carbon-heteroatom bonds from readily available starting materials. Traditional hydrogenation methods typically require precious or semi-precious transition metal complexes or finely divided powders. Iron-based catalysts offer several advantages over more traditional ‘noble’ metal systems due to the high abundance, long-term availability, low cost and low toxicity of iron. To date, the most powerful iron-catalysed hydrogenation and hydrofunctionalisation reactions have required either highly air-sensitive iron(0) complexes or iron(II) complexes activated with an extremely reactive, pyrophoric organometallic reagent. An operationally simple and environmentally benign formal hydrogenation protocol has been developed using a simple iron(III) salt and NaBH4; an inexpensive, bench stable, stoichiometric reductant. This reaction has been applied to the reduction of terminal alkenes (22 examples, up to 95% yield) and nitro groups (26 examples, up to 95% yield) in ethanol, under ambient conditions (Scheme A1). Two novel series of structurally related alkoxy-tethered N-heterocyclic carbene (NHC) iron(II) complexes have been developed as catalysts for the regioselective hydroboration of alkenes. Significantly, Markovnikov selective alkene hydroboration with pinacolborane (HBpin) has been controllably achieved for the first time using an iron catalyst (11 examples, 35-90% isolated yield) with up to 37:1 branched:linear selectivity (Scheme A2). anti-Markovnikov selective alkene hydroboration was also achieved using catecholborane (HBcat) and modification of the ligand backbone (6 examples, 44-71% yield). In both cases, ligand design has enabled activator-free iron catalysis.