Purification of a metathesis mixture can give you all sorts of problems (especially when using high catalyst loadings). Sometimes you need multiple columns to get a colorless product. Sometimes residual ruthenium can cause the product to isomerize during distillation or decompose over time. Numerous methods have been reported for the removal of metathesis catalysts after a reaction. In general, you need a ligand or adsorbent that binds ruthenium better than your product, or a reagent that will react with the residual ruthenium preferentially. Unfortunately the optimal process tends to vary on a case by case basis.
Published Techniques
- P(CH2OH)3 (Grubbs, Tetrahedron Lett. 1999, 40, 4137). The most versatile technique out there. This water-soluble phosphine lets you wash the ruthenium away with an aqueous workup. At least 20 equiv. are necessary for efficient ruthenium removal.
- P(CH2OH)4Cl + KOH (Pederson, Adv. Synth. Catal. 2002, 344, 728). This generates P(CH2OH)3 from the inexpensive salt.
- CNCH2CO2K (Diver, Org. Lett. 2007, 9, 1203). This polar isocyanide is much faster than P(CH2OH)3 in quenching the catalyst (~30min) and the complex can be removed by filtration through silica. Unfortunately the isocyanide is not commercially available and takes two steps to prepare.
- Hydrogenation (Wang, Org. Process Res. Dev. 2008, 12, 226). Hydrogenation with Pd/C following an RCM reaction resulted in removal of residual ruthenium, which is presumably adsorbed onto the solid catalyst.
- Basic solution of cysteine (Wang, Tetrahedron 2009, 65, 6291). After a RCM in EtOAc, the crude mixture was washed with an aqueous solution of cysteine and NaOH.
- Activated carbon (Kim, Org. Lett. 2003, 5, 531). Sequential treatments with silica gel, activated carbon, and column chromatography.
- Amine-functionalized mesoporous silicates (Crudden, Org. Lett. 2006, 8, 2663). This method doesn’t require an aqueous wash or chromatography but a large amount of the adsorbent is used.
- DMSO or Ph3PO (Georg, Org. Lett. 2001, 3, 1411). Stirring overnight with 50 equiv. followed by column chromatography.
- Pb(OAc)4 (Paquette, Org. Lett. 2000, 2, 1259). A slight excess (1.5 equiv. per ruthenium) was used followed by silica filtration.
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Our group has developed a method using 3-mercaptopropionic capped Iron/iron oxide nanoparticles, which may have advantages using magnetic removal.
Err, I guess it would help if I gave the reference. Sorry about that!
Macdonald, Langmuir, 2008, 24 (14), pp 7169–7177. DOI: 10.1021/la8006734
This has the potential to be a convenient and inexpensive process. Are there other methods out there?
Wait for an soon to be published Tet. Lett, feature article using hydrogen peroxide! Cheap as chips!
alchemist must have bee talking about the recent David Knight TL paper (Article in Press published Nov. 26, doi: 10.1016/j.tetlet.2009.11.092). They use a simple wash with 15% hydrogen peroxide to kill the catalyst. Worried about over oxidation? The RuO2 that is formed in the process reacts with H2O2 to give H2O and O2, destroying excess peroxide in the process. There are bound to be some functional group incompatibilities, but if it’s as cheap, easy, and effective as it seems, it’s definitely worth a try…