Ring-Closing Metathesis and Cross Metathesis – Erwann Grenet Phillips Triolefin Process (1964) with Mo(CO)6 AlO2, WO3 SiO2 Nobel Prize in 2005

Ring-Closing Metathesis and Cross Metathesis – Erwann Grenet Overview of the available catalysts 167 CHF/g 3505 582 CHF/g 3279 Price on Sigma-Aldrich Number of ref on SciFinder 3500 CHF/g 315 612 CHF/g 343 392 CHF/g 1392 For Mo-Schrock: Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare, M.; O'Regan, M. J. Am. Chem. Soc. 1990, 112, 3875–3886. For G-I : Schwab, P.; France, M.B.; Ziller, J.W.; Grubbs, R.H. Angew. Chem. Int. Ed. 1995, 34, 2039-2041. For G-II : Scholl, M.; Trnka, T.M.; Morgan, J.P.; Grubbs, R.H., Tetrahedron Lett. 1999, 40, 2247-2250. For GH-I: Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791–799. For GH-II: Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168–8179.

< = Ring-Closing Metathesis and Cross Metathesis – Erwann Grenet Molybdenum-based catalysts Ruthenium-based catalysts Schrock vs Grubbs ACTIVITY STABILITY Efficient for very hindered olefin Broad tolerance Alkyne metathesis Non tolerant to oxo functionnal groups (carbonyl, hydroxyl, etc) Non tolerant to phosphine, sulfure or electron-rich amine groups < = “They are the two wings of the same angel. The angel can't fly if you clip either one.” Amir Hoveyda

Phosphine-free ligands Ring-Closing Metathesis and Cross Metathesis – Erwann Grenet Phosphine ligands NHC ligands 1st gener. vs 2nd gener. Similar group tolerance and thermal stability Better catalytic activity Phosphine ligands Phosphine-free ligands - Faster kinetic Grubbs vs Hoveyda Trouble with sulfure group -

Ring-Closing Metathesis and Cross Metathesis – Erwann Grenet The new modified catalysts Grubbs III (G-III) Piers II (P-II) 605 CHF/g 24 555 CHF/g 456 690 CHF/g 96 nitro-Grela 2924 CHF/g 456 Stewart-Grubbs New battle in perspective with ruthenium catalysts? Mo-catalyst in paraffin pellets For G-III : Sanford, M. S.; Love, J. A.; Grubbs, R. H. Organometallics 2001, 20, 5314–5318. For Piers: Romero, P. E.; Piers, W. E.; McDonald, R. Angew. Chem. Int. Ed. 2004, 43, 6161-6165. For Stewart-Grubbs: Stewart, I. C.; Douglas, C. J.; Grubbs, R. H. Org. Lett. 2008, 10, 441-444. For nitro-Grela: Angew. Chem. Int. Ed. 2002, 41, 4038-4040. For Schrock paraffin pellets: Nguyen, T. T., Koh, M. J.; Shen, X.; Romiti, F.; Schrock, R. R.; Hoveyda, A. H. Science 2016, 352, 569-574.

nitro-Grela Piers II (P-II) Stewart-Grubbs Schrock HG-I HG-II Grela 167 CHF/g 3505 582 CHF/g 3279 612 CHF/g 343 392 CHF/g 1392 3500 CHF/g 315 555 CHF/g 456 nitro-Grela 2924 CHF/g 160 Piers II (P-II) 605 CHF/g 24 Stewart-Grubbs 690 CHF/g 96 Price on Sigma-Aldrich Number of ref on SciFinder For Mo-Schrock: Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare, M.; O'Regan, M. J. Am. Chem. Soc. 1990, 112, 3875–3886. For G-I : Schwab, P.; France, M.B.; Ziller, J.W.; Grubbs, R.H. Angew. Chem. Int. Ed. 1995, 34, 2039-2041. For G-II : Scholl, M.; Trnka, T.M.; Morgan, J.P.; Grubbs, R.H., Tetrahedron Lett. 1999, 40, 2247-2250. For HG-I: Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791–799. For HG-II: Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168–8179. For G-III : Sanford, M. S.; Love, J. A.; Grubbs, R. H. Organometallics 2001, 20, 5314–5318. For nitro-Grela: Angew. Chem. Int. Ed. 2002, 41, 4038-4040. For Piers: Romero, P. E.; Piers, W. E.; McDonald, R. Angew. Chem. Int. Ed. 2004, 43, 6161-6165. For Stewart-Grubbs: Stewart, I. C.; Douglas, C. J.; Grubbs, R. H. Org. Lett. 2008, 10, 441-444. 1990 1995 1999 2000 2001 2002 2004 2008 Schrock HG-I HG-II Grela S-G G-I G-II G-III P-II