The second revolution in ruthenium-catalyzed olefin metathesis was triggered by substituting one phosphine ligand in 1st generation catalysts with a more basic N-heterocyclic carbene (NHC). The activity of these 2nd generation (NHC-bearing) catalysts superseded that of 1st generation while maintaining functional group tolerance.
The 2nd generation Grubbs catalyst (I) is undoubtedly the most well-known example of an NHC-bearing olefin metathesis catalyst. Discovered in 1999, it remains a popular catalyst, and over the past decade various modifications of the ligands have helped expand its applications scope.
For example, Hoveyda introduced his phosphine-free catalyst featuring a chelating benzylidene ether ligand in 2000. The 2nd generation Hoveyda-Grubbs catalyst (II) is particularly efficient for metathesis involving highly electron-deficient olefins such as acrylonitrile and fluorinated alkenes. Several researchers have since modified the steric and electronic properties of the “Hoveyda ligand” to further tune the initiation rate of the Hoveyda-type catalysts.
Very fast-initiating second generation catalysts have also been designed, and include the bis-pyridine III and the Piers catalysts (IV). Bis-pyridine catalysts have a unique 6-coordinate structure, and are mostly employed in ROMP, whereas Piers catalyst is a rare example of a four-coordinate fourteen electron catalyst able to initiate metathesis reactions at very low temperatures.
Modifications of the NHC moiety have also played a major role in the advent of second generation catalysts. For example, catalysts with improved activities were obtained with saturated (vs unsaturated) NHCs, and aryl (vs alkyl) groups at nitrogen. While mesityl groups are the most common substituent on nitrogen, they are by no means the only one to consider. For example, the first highly efficient ring closing metathesis reaction to form tetra-substituted olefins required the use of an NHC featuring the less bulky tolyl (ortho-methyl) groups at nitrogen (V).
Overall, the catalysts mentioned above highlight significant advancements in olefin metathesis catalyst technology. Efforts continue toward developing catalysts that can address particularly difficult olefin metathesis reactions.