The ubiquitous 1st generation Grubbs catalyst, (PCy3)2Cl2Ru=CHPh, has been utilized for the synthesis of natural products, small molecules, and polymeric materials via olefin metathesis methodologies. In addition, the catalyst has been an extremely useful precursor towards the synthesis of new, more active N-heterocyclic carbene (NHC) bearing catalysts including the 2nd generation Grubbs catalyst (I). However, the synthesis of NHC-containing catalysts with a similar Grubbs motif bearing different phosphines can be difficult or low yielding due to sterics, electronic, and equilibrium effects. As a result, most of the 2nd generation-type catalysts contain tricyclohexyphosphine (PCy3) as the labile phosphine.
In 2001, the Grubbs group reported a convenient method for phosphine exchange of 2nd generation-type catalysts. The strategy involved the synthesis of a versatile precursor II, bearing pyridine ligands in place of phosphine. Interestingly, the kinetics of pyridine substitution for PCy3 suggested an associative mechanism – a marked contrast with the dissociative mechanism observed with olefins. The bispyridine ruthenium species II can be precipitated from pentane and washed to remove the PCy3 that’s released. It then readily reacts with phosphines, even those less basic than PCy3, to displace pyridine and form new complexes of the form III in high yield and purity. The result is a simple, high-yielding procedure for phosphine exchange in cases where PCy3 cannot be substituted directly.