Iron-catalyzed Cross Coupling reactions: From Rust to a Rising Star

1. Iron-catalyzed Cross Coupling reactions: From Rust to a Rising Star Weijun Liu

2. Transition metal catalyzed cross couplings have seen incredible advances and applications, have wide scope and compatibility. But…..typically use palladium and nickel which are generally toxic and expensive. Expensive and/or sensitive ancillary ligands are required. Alkyl iodides, bromides and triflates are best. With special ligands alkyl chlorides may be used.

3. Iron: A More Practical Alternative • Iron is one of the most abundant metals on earth. (5.6% of earth’s crust. 4th most abundant element after oxygen, silicon, and aluminum. Nickel is 0.0084%, palladium is 0.0000015%, gold is 0.0000004% of Earth’s continental crust.) • 2. Cheap • •PdCl2: $4005/150g $26.70/g • •NiCl2: $98.40/250g $0.39/g • •FeCl3: $30.40/1kg $0.03/g • 3. nontoxic • •Prevalent in biological systems

4. Content: • Early Examples • 2. Alkenyl Derivatives as Substrates • 3. Aryl Derivatives as Substrates • 4. Alkyl Derivatives as Substrates • 5. O, N, S-Arylation • 6. Oxidative Cross-coupling

5. Early Examples J. Kochi, J. Am. Chem. Soc.1971, 93, 1487

6. Kochi, J. J. Org. Chem.1976, 41, 502

7. 2. Alkenyl Derivatives as Substrates NMP as cosolvent Cahiez, G. Synthesis1998, 1199

9. Cahiez, G.Synthesis1998, 1199

10. 60% 60% Cahiez, G.; Knochel, P.Synlett2001, 1901

11. 3. Aryl Derivatives as Substrates Furster, A.Angew. Chem., Int. Ed.2002, 41, 609

14. Proposed Formal Catalytic Cycle

15. 4. Alkyl Derivatives as Substrates Furster, A.Angew. Chem., Int. Ed.2004, 43, 3955

16. Furster, A.Angew. Chem., Int. Ed.2004, 43, 3955

17. Furster, A.Angew. Chem., Int. Ed.2004, 43, 3955

18. Only tertiary halides and alky chlorides were found be inert.

19. Nakamura, E. J. Am. Chem. Soc.2004, 126, 3686

22. Hayashi, T. Org. Lett.2004, 6, 1279

23. Cossy, J.Angew. Chem., Int. Ed.2007, 46, 6521

24. 51% Chai, C.L.L.Adv. Synth., Catal.2007, 349, 1015

25. 5. O, N, S-Arylation Bolm, C.Angew. Chem., Int. Ed.2007, 46, 8862

26. Bolm, C.Angew. Chem., Int. Ed.2007, 47, 586 Bolm, C.Angew. Chem., Int. Ed.2008, 47, 2880

27. 6. Oxidative Cross-coupling Iron-Catalyzed Homo-Coupling FeI/FeIII or Fe0/FeII Fe-II/Fe0 Cahiez, G. Org. Lett.2005, 7, 1943

28. Cahiez, G. J. Am. Chem. Soc.2007, 129, 13788

29. Oxidative Heterocoupling Cahiez, G.Angew. Chem., Int. Ed.2009, 43, ASAP

30. Iron-Catalyzed Direct Arylation through Directed C-H Bond Activation

31. Nakamura, E. J. Am. Chem. Soc.2008, 130, 5858

32. Iron-Catalyzed Chemoselective ortho Arylation of Aryl Imines by Directed C-H Bond Activation Nakamura, E.Angew. Chem., Int. Ed.2009, 48, ASAP

33. Li, Z.-P.; Li, C.-J.Angew. Chem., Int. Ed.2007, 46, 6505

34. X = N, O, S Li, Z.-P.Angew. Chem., Int. Ed.2008, 47, 7497

35. Summary 1. Iron catalysts activate alkenyl, aryl, and alkyl derivatives. 2. Iron catalysts activate aryl chlorides, triflates and tosylates under ligand free conditions. 3. Iron-catalyzed cross-coupling shows excellent functional group tolerance. 4. Iron-catalyzed cross-coupling needs only short reaction (typically 5-30 min) time and are performed at low temperatures (typically -20 oC to 0 oC). 6. Iron salts has been successfully applied in the C-H bond activation and oxidative coupling reactions But the iron-catalyzed cross coupling is not nearly as mature as its palladium and nickel counterparts. And the reaction mechanisms are needed to be proved.