Storage of Grubbs Catalysts

“Anhydrous” means different things to different people. – Seth Herzon I’m sure you’ve seen it written, probably somewhere on this website, that ruthenium olefin metathesis catalysts are stable to air and water. But stability is not a black and white issue. It’s all grey area. So exactly how grey are Grubbs catalysts? For a typical […]

Ring Closing Metathesis Reaction Planning

Ring closing metathesis (RCM) has evolved into one of those coveted “predictable” reactions in organic synthesis. Sure, there are things that can go wrong, but for forming unstrained rings, it’s a great way to go. Substrate selection As with any time using a Grubbs catalyst system, you want to avoid certain functional groups. Coordinating groups […]

Functional Group Tolerance/Protecting Group Strategy

The Grubbs catalyst and all of its brothers and sisters are tolerant of most organic functional groups, but there are some bad actors to avoid… Strong Lewis bases can coordinate to the catalyst and de-activate it. Try to avoid (or protect) phosphines, thiols/sulfides, basic unhindered amines, pyridines, ureas, isonitriles, etc. The easiest way to protect […]

Removing Oxygen and Peroxides for High Catalyst Efficiencies

It’s well known that olefins can build up peroxides over time, especially if stored at room temperature and exposed to light. Oxygen and peroxide impurities can accelerate the decomposition of an olefin metathesis catalyst and decrease the efficiency of the metathesis significantly. Of course higher catalyst loadings can fix that, but it’s not a perfect […]

Benefits of Exploring Metathesis Catalyst Addition Methods

Metathesis catalysts can be added to the reaction mixture as a solid, a solution (methylene chloride, etc.) or as a suspension. If you’re not concerned with optimizing for the lowest catalyst loading, you can usually get away with whichever is easiest for your process. But if you have a challenging reaction or want to use […]

Choosing the Best Metathesis Catalyst for a Reaction

I decide to run an organometallic coupling reaction. I go to the literature to see what conditions people have used for similar transformations, and I’m overwhelmed. Every paper I see uses a different combination of precatalyst, ligand, additive(s), and solvent.  Which is best? Are they different for a reason, or is it a matter of […]

Solvent Considerations in Ruthenium Catalyzed Metathesis Reactions

I dare you to find an issue of Organic Letters in the past five years that doesn’t have an example of ruthenium-catalyzed olefin ring closing metathesis. Chances are that most of the examples are run in CH2Cl2 at a concentration of <0.1 M. And they probably work pretty well. If you ask any of the […]

Effect of Temperature on Olefin Metathesis Reactions

As is the case with many chemical reactions, temperature can be both friend and foe.  Heating a reaction will invariably make it go faster, but can also increase the rate of side reactions and decomposition. For ruthenium catalyzed olefin metathesis reactions, choosing the right temperature for a reaction invariably comes down to trial and error. […]

Cross Metathesis Reaction Planning

There’s nothing more frustrating to a synthetic chemist than a reversible reaction. We incur great expense to prepare reactive reagents (MeMgBr, LiAlH4, Br2, PhI(OAc)2, etc.) that do their thing and then just stand by and watch after they’re done. I think this is in part why RCM was so quickly adopted by the synthetic community. […]

Inhibiting Olefin Isomerization

Olefin isomerization/migration can be an annoying side reaction of olefin metathesis, in no small part because the side products are usually difficult to separate from the desired product. The isomerization is catalyzed by metal hydride species formed in the decomposition of the catalyst (see Schmidt, Eur. J. Org. Chem. 2004, 1865 for a review). General […]

Metathesis Catalyst Removal Techniques

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 […]