1. IMPROVED RUTHENIUM CATALYSTS FOR Z-SELECTIVE OLEFIN METATHESIS Benjamin K. Keitz, Koji Endo, Paresma R. Patel, Myles B. Herbert, and Robert H. Grubbs J. Am. Chem. Soc. 2012, 134, 693–699. Shawn K. Collins Université de Montréal Department of Chemistry Centre for Green Chemistry and Catalysis shawn.collins@umontreal.ca Web: http://www.mapageweb.umontreal.ca/collinss/ http://www.mapageweb.umontreal.ca/collinss/ CHARETTE/COLLINS LITERATURE MEETING Université de Montréal (UdeM) October 11 th, 2012 Montréal, Québec

2. CROSS METATHESIS: GENERALIZED MECH USING GRUBBS II For a review on catalytic cross-metathesis, see: (a) Blechert, S.; Connon, S. J. Angew. Chem., Int. Ed. 2003, 42, 1900; (b) Vernall, A. J.; Abell, A. D. Aldrichimica Acta 2003, 36, 93; (c) For industrial applications of cross metathesis, see: Pederson, R. L.; Fellows, I. M.; Ung, T. A.; Ishihara H.; Hajela, S. P. Adv. Synth. Catal. 2002, 344, 728. First proposed by Chauvin: Herrison, J. L.; Chauvin, Y. Makromol. Chem. 1970, 141, 161. and later expanded upon by Katz: Katz, T. J.; McGinnis, J. L. J. Am. Chem. Soc. 1975, 97, 1592.

3. R1R1 Z:EZ:EYield of cis-product (%) (CH 2 ) 5 CH 3 9:156 (CH 2 ) 7 CH 3 8.5:172 (CH 2 ) 3 Br7.3:145 (CH 2 ) 2 Br9:117.5 (CH 2 ) 4 OTBS6.7:190 (CH 2 ) 3 OTBS5.6:168 (CH 2 ) 2 OTBS5.3:173 CH 2 TMS3:176 o-MeOC 6 H 4 CH 2 9:172 (CH 2 ) 6 CH=CH 2 8:153 (CH 2 ) 2 C(O)OBn5.6:144 (CH 2 ) 3 CH(OMe) 2 7: 179 CH 2 CMe 2 CH 2 CH(OMe) 2 3: 164 Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117, 5162. Z-SELECTIVE METATHESIS (PREVIOUS): SUBSTRATE CONTROL

4. Product Z:EZ:E Yield (%) Product Z:EZ:E Yield (%) 4:1883:176 3:1813:179 4:1919:183 Randl, S.; Gessler, S.; Wakamatsu, H.; Blechert, S. Synlett 2001, 430.

5. ProductE:ZE:Z Yield (%) ProductE:ZE:Z Yield (%) 43:577996:480 42:5878>98:294 1:9959>99:186 83:177493:760 Kim, M.; Lee, D. Org. Lett. 2005, 7, 1865. Z-SELECTIVE METATHESIS (PREVIOUS): SUBSTRATE CONTROL

6. Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16630. Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST CONTROL

7. Meek, S. J.; O'Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 471, 461-466.

8. Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST CONTROL Yu, M.; Wang, C.; Kyle, A. F.; Jakubec, P.; Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 479, 88-93.

9. Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST SYNTHESIS Modification of adamantyl group or mesityl group either destroyed reactivity or prevented metalation of the adamantyl group… …current manuscript focuses on modification of the anionic group!

10. Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST SYNTHESIS

11. Z-SELECTIVE METATHESIS (PREVIOUS): SUBSTRATE CONTROL

12. Z-SELECTIVE METATHESIS (PREVIOUS): OLEFIN BINDING

14. Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST SYNTHESIS Bulky ligands caused faster initiation …strange for Hov- type cats Monodentate ligands were essentially non- metathesis active… Faster initiation did not guarantee better catalysts… Some changes to aryl group (that did give catalysts) did not affect rate (ie Cl sub for Me)…

15. Z-SELECTIVE METATHESIS (PREVIOUS): SUBSTRATE CONTROL NO2 cat. has little secondary metathesis events

16. SUMMARY. 1)New C−H activated ruthenium catalysts for Z-selective olefin metathesis. Adjusting the ligand environment around the metal center has yielded significant insight into the initiation behavior, activity, and selectivity. 2)Catalysts are capable of ca. 1000 turnovers in several cross- metathesis reactions with very low loadings and do not require reduced pressures, high temperatures, or rigorous exclusion of protic solvents in order to operate effectively. 3)Secondary metathesis events are also relatively slow for the majority of substrates, meaning that significant reaction optimization should not be required.