1. Rhodium Catalyzed Direct C-H Functionalization 陈殿峰 2012.10.13

2. Outline : 1.Introduction 2.Oxidative coupling 3.Nucleophilic Addition 4.Other Reactions 5.Conclusion 2

3. 1. Introduction 3

4. 2. Oxidative Coupling DG = See: F. Glorius, J. A. Ellman, Sukbok Chang,T. Satoh, M. Miura Z.-J. Shi, X.-W. Li, T. Rovis, N. Cramer Oxidizing DG 4 Heck Type

5. Arylation Double C-H activation F.Glorious, Angew. Chem. Int. Ed. 2012, 51, 2247 M. Miura, Angew. Chem. Int. Ed. 2012, 51, 5359 2. Oxidative Coupling 5

6. Alkynylation Y= DG 2. Oxidative Coupling Alkynylation T. Satoh, M. Miura, Angew. Chem. Int. Ed. 2008, 47, 4019-40226

7. Alkynylation 2. Oxidative Coupling C. Zhu, Chem. Eur. J. 2011, 17, 12591-12595 Alkynylation 7

8. F. Glorius, J. Am. Chem. Soc.,2012,134, 8298-8301 2. Oxidative Coupling Halogenation Path a : nucleophilic addition Path b : high oxidation-state Rh(V) Alkynylation 8 B.-Q. Wang, J. Am. Chem. Soc., 2012, 134,16163

9. Oxidizing DG Background X.-L. Cui, Y.-J. Wu, J. Am. Chem. Soc., 2009, 131,13888 2. Oxidative Coupling W.-Y. Yu, J. Am. Chem. Soc, 2010, 132,12862 J. F. Hartwig J. Am. Chem. Soc, 2010, 132, 3676 9

10. N. Guimond, J. Am. Chem. Soc., 2010, 132, 6908 Oxidizing DG 2. Oxidative Coupling N. Guimond, J. Am. Chem. Soc, 2011, 133, 6449 10

11. Z.-J. Shi, Angew. Chem. Int. Ed., 2012, 52, 3948 Oxidizing DG 2. Oxidative Coupling C-N Cleavage 11

12. 2. Oxidative Coupling For Rh catalyzed oxidative coupling: 1). Rh(III) is generally efficient catalyst because its high oxidation- state facilitates β-elimination ； 2). Versatile DGs have been well established whereas DG-free coupling reactions are still rare; 3). The fact that more than stoichiometric metal-oxidants (Cu 2+, Ag + ) are generally needed callsfor eco-friendly pathways (air). 4). Harsh reaction conditions (high temprature, excess oxidant, strong base or acid) lead to poor functional group tolerence. 5). Limited examples involving sp 3 C-H activation are reported. 12

13. Direct Addition 3. Nucleophilic Addition 13

14. 3. Nucleophilic Addition Direct Addition 14

15. R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2008, 130, 3645 3. Nucleophilic Addition Direct Addition R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2012, 134, 4064 15

16. 3. Nucleophilic Addition Direct Addition S.-M. Ma, J. Am. Chem. Soc. 2012, 134, 9597 C.-H. Cheng, Angew. Chem. Int. Ed., 2012, 51, 197 16

17. 3. Nucleophilic Addition Direct Addition R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc, 2011. 133, 1248 J. Am. Chem. Soc, 2012. 134, 1482 R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc, 2011. 133, 11430 Others Acceptors Imine: Isocyanates:Aldehyde: Z.-J. Shi, Org. Lett, 2012, 14, 4498 Z.-J. Shi, Org. Lett, 2012, 14, 636 Org. Lett, 2012, 14, 4498 17

18. Notes: 1.DG as acceptors; 2. Strained direct addition 3. Nucleophilic Addition Delayed Addition T. Satoh, M. Miura. Chem. Commun. 2009, 5141 18

19. N. Cramer, Angew. Chem. Int. Ed, 2010, 49, 8181 N. Cramer, Angew. Chem. Int. Ed, 2011, 50, 11098. 3. Nucleophilic Addition P.-J. Zhao, Chem. Eur. J. 2010, 16, 2619 Delayed Addition 19

20. C.-H. Cheng, Angew. Chem. Int. Ed, 2011, 50, 4169 F. Glorius, J. A m. Chem. Soc. 2011, 133, 2154 3. Nucleophilic Addition Delayed Addition 20

21. 3. Nucleophilic Addition For nucleophilic C-Rh : 1). Rh(I)/Rh(III) are both efficient catalysts ； 2). More type of acceptors are needed to developed and three components reaction has not been reported; 3). Alkenes or other moities that could insert C-Rh bond may take the place of alkynes 4). Limited assymetric examples have been demonstrated, which indicates, in a way, the limitation of existing chiral ligands. 21

22. 4. Other Reactions M. Murakami, J. A m. Chem. Soc. 2007, 129, 12086 Nucleophilic addition via C-C Cleavage M. Murakami, J. A m. Chem. Soc.2012, 134, ASAP. Oxidative Coupling via C-C Cleavage Z.-J. Shi, J. A m. Chem. Soc.2011, 133, 15244. 22

23. 4. Other Reactions Carboacylation of Olefins G.-B. Dong, Angew. Chem. Int. Ed, 2012, 51, 7767 Ring Open of VCP Z.-X. Yu, J. A m. Chem. Soc.2011, 134, 398. Z.-X. Yu, Angew. Chem. Int. Ed, 2011, 50, 2144 23

24. Z.-X. Yu, J. A m. Chem. Soc.2010, 132, 4542. 4. Other Reactions 24

25. 5. Conclusion: 25 1). Rh(I)/Rh(III) are versatile catalysts towards C-H bond activation; 2). Necessary DGs limite the substrates scope; 3). Direct sp 3 C-H functionalization remains challenging; 4). Mild reaction conditions are demanded for better functional group tolerence. 5). New chiral ligands or novel asymmetric catalytic circles would highlight Rh catalyzed C-H activation.