Cross metathesis using Grubbs Catalysts is basically “dump and stir” chemistry, which means that you can generally make your target compound the first time you try. If you browse through the literature, you’ll see plenty of examples of successful reactions using Grubbs Catalysts, but most of these use >1 mol% of catalyst. This is fine if your goal is to quickly get your hands on your product, but whenever it comes time to think about scaling up, using as little catalyst as possible becomes important.
A recent report from the Slugovc group addressed the question of how much catalyst was required to achieve good yields in a cross metathesis reaction with ethyl acrylate.1 Because of the electron-poor double bond, acrylates tend to be inefficient in olefin metathesis reaction. However, because acrylates are slow to react with themselves, they tend to give selective cross metathesis products with unactivated olefins.
Slugovc studied the reaction between ethyl acrylate and 1,9-decadiene, which forms the C12 diester as a mixture of E/Z isomers. He used commercially available substrates without any purification, screening a number of 2nd Generation Catalysts and reaction temperatures. At 80 °C, the reaction went to completion (<1% unfunctionalized olefin remaining) with as little as 0.02 mol% catalyst loading of the phosphine-free catalysts shown below.
To obtain high yields, the authors note that ethyl acrylate must be used in excess (5 equiv) and as the solvent. If the reaction is run with less acrylate or with an additional solvent, the yields suffer.
It’s great to see people pushing the limits of low catalyst loadings. I wonder what process improvements will bring these catalyst levels even further down…
1 Abbas, M.; Slugovc, C. Tetrahedron Lett., 2011, 52, 2560-2562.