The first asymmetric Mo-based metathesis catalyst was reported by Grubbs way back in 1996 (J. Am. Chem. Soc. 1996, 118, 2499). Since then, a large number of other chiral catalysts have been developed, based both on Ru and Mo (some structures shown below). While Mo-based catalyst generally work better for RCM reactions, both Mo and Ru catalysts were shown to be efficient in ring opening/cross metathesis (Org. Lett. 2007, 9, 2871) and can be complementary for different substrates. The development of an efficient catalyst for asymmetric cross metathesis still remains a challenge (Angew. Chem. Int. Ed. Engl. 2006, 45, 7591).
Mo-based complexes offer very attractive opportunities for the design of efficient chiral catalyst due to the presence of alkoxide ligands that don’t dissociate from the metal center during the metathesis catalytic cycle. This has been one of the areas of focus of the fruitful collaboration between Richard Schrock (MIT) and Amir Hoveyda (Boston College). A recent example with exquisite selectivity was developed in the context of the synthesis of the alkaloid quebrachamine (J. Am. Chem. Soc. 2009, 131, 943; Nature 2008, 456, 933). The desymmetrization substrate was a challenge for even racemic RCM catalysts with its hindered olefins, basic amine, and presumably strained transition state to ring closure.
The newly designed catalyst represents a fundamentally new approach to asymmetric olefin metathesis catalysts in that it’s stereogenic at the metal, bearing two electronically distinct monodentate anionic ligands: the donor ligand is a chiral BINAP-derivative and the acceptor is an imidazole. The choice of these monodentate ligands makes the complex less rigid than conventional chiral catalysts, which is thought to accelerate both substrate-catalyst association and metallocyclobutane decomposition.
The performance of the new catalysts is really remarkable: the reaction is done with 1 mol% catalyst in one hour to yield the desired product in 84% isolated yield and 96% ee! The catalyst can be generated in situ by adding an enantiopure alkoxide to a bis-imidazole Mo species. Furthermore, the whole procedure can be performed in a hood instead of a glove box!