Ring closing metathesis B. JACS,
Every paper I see uses a different combination of precatalyst, ligand, additive sand solvent.
Are they different for a reason, or is it a matter of taste? There are exceptions to these rules, but in general, If a 1st generation catalyst can do it, a 2nd generation catalyst can do it.
If a phosphine catalyst can do it, a Hoveyda catalyst can do it Therefore a good starting point for most metathesis reactions is the 2nd Generation Hoveyda-Grubbs catalyst. It usually works when others work, and sometimes works when others fail. The 1st generation catalysts have a few things going for them, though.
Even though the overall cost for a reaction with a 1st generation catalyst is often more expensive than with a 2nd Gen. Sometimes this is a good thing.
Do you have temperature limitations? In general, the ruthenium metathesis catalysts are designed to be used at or around room temperature. Is your substrate extra hindered?
The N-phenyl catalysts shown below an alkyl-substituted NHC backbone is required for stability is a good example of this. The commercially available o-tolyl catalysts serve the same purpose but are easier to prepare.
But here are a few more special cases where one catalyst or class of catalysts outperforms: The Grubbs catalyst-acrylonitrile adduct think of Grubbs catalyst with a cyano on the alkylidene instead of a phenyl is slow to initiate.
Grubbs Cross Metathesis Jacs. A General Model for Selectivity in Olefin Cross Metathesis A General Model for Selectivity in Olefin Cross Metathesis. Grubbs Cross–Metathesis Pathway for a Scalable Synthesis of γ-Keto-α, β-unsaturated Esters. Fast-Initiating. These types of metathesis are called ring closing metathesis, cross metathesis or ring opening polymerization, respectively. Types of Metathesis Ring Opening Metathesis Truett, et al. JACS. Olefin metathesis is already regarded as an important way to make carbon-carbon bonds, but the reaction could become even more practical, thanks to a new, highly active, water-soluble catalyst.
Likely due to a combination of sterics and electronics, it means that once phosphine traps the active intermediate, it deactivates it. The way to solve this problem is either to a use a phosphine-free catalyst, such as a Hoveyda or bisbromopyridine catalyst, or b use a Lewis acid additive to sequester phosphine, keeping it from causing trouble.
Both methods have been used successfully for this challenging transformation. In order to effect a controlled living polymerization, you need a catalyst which has a rate of initiation faster than the rate of propagation. Typically, people will use the bisbromopyridine catalyst shown above more recently, reports are surfacing of the bromine-free bispyridine ruthenium complex being used for this.
Cross Metathesis to make Trisubstituted Olefins.
A singular report from the Grubbs group in showed that cross metathesis to make trisubstituted olefins is more efficient with catalysts containing bulkier carbene ligands structure shown below, first reported by Ken Wagener.
They rationalize the counterintuitive data by arguing that the less hindered catalysts are more apt to undergo non-productive turnover events. I encourage you to read the arguments from the source Grubbs Org.
What am I missing?Olefin metathesis is already regarded as an important way to make carbon-carbon bonds, but the reaction could become even more practical, thanks to a new, highly active, water-soluble catalyst.
Seebach et al JACS L S O L S PPh3+ S PPh3 LS L O + - O LS PPh3 L S + S L S O L Ph3P L PPh3 S O S L - Ph3P=O L L SS Z-olefins - "Stabilized ylides" give predominantly E-olefins Ph3P CO2Me + L S O L CO2Me S_ Grubbs olefin metathesis.
Olefin cross metathesis. Olefin metathesis. Brønsted bases of widely varying strength are shown to decompose the metathesis-active Ru intermediates formed by the second-generation Hoveyda and Grubbs catalysts. Alkene Synthesis C/ Olefin Metathesis R 1 R 2 R 4 R 3 R 1 R 4 R 2 R 3 + + is known as olefin metathesis Reviews: Grubbs Acc.
Chem. Res. , 28, Hoveyda Top. Organomet. Organomet. Cross-metathesis is a powerful method for the rapid synthesis of simple and complex olefinic building blocks. Grubbs catalyst and Hoveyda-Grubbs catalyst are.
Olefin cross metathesis is a particularly powerful transformation that has been exploited extensively for the formation of complex products.
Until recently, however, constructing Z‐olefins using this methodology was not possible.