1. 化 学 系 Department of Chemistry Catellani Reaction 2011.04.09

2. Introduction Mechanism Synthetic Applications Contents Conclusions 1

3. The Nobel Prize in Chemistry 2010 Richard F Heack University of Delaware, Newark,DE,USA Ei-ichi Negishi Purdu University, West Lafayetle,IN,USA Akira Suzuki Hokkaido University, Sapporo,Japan For palladium-catalyzed cross-coupling reactions in organic synthesis. Introduction 2

4. Marta Catellani 1971,obtained Italian laurea under supervition of Prof. G. Casnati at the University of Parma. 1977,started to work on homogeneous Catalysis with group Ⅷ metals, G.Casnati Group 1978-1979, Postdoc, UC, Prof. J. Halpern 1989-1990, short periods in Sheffied,Tsukuba,Russia and China. 1990-present, full professor at Uiversity of Parma. Catellani M, Angrew. Chem. Int. Ed. 1997,36,119-122. Introduction 3

5. Role of Norbornene : 1. Essential for this reaction to occur; 2. Plays as a catalyst; 3. More than stoichiometric norbornene is necessary norbornene...... Catellani Reaction is defined as Norbornene-mediated Ortho C-H Functionalization. 4 R2-YR1-X

6. Mechanism R 1 = Alkyl, Aryl R 2 =Aryl, Alkenyl, H, CN R = H, or bulky substisuents 5

7. Oxidation Addition 1 R 1 =alkyl, path 1 predominates. R 1 =aryl, it depends on Ligands. Path 1 Path 2 6

8. Carbopalladation of Norbornene 1. High reactivity (strain energy 90.4 kJ/mol) 2. Superstoichiomeric quantities Favored 7

9. Phenylnorbornylpalladadium( Ⅱ ) dimer PNP dimer Inoue M, Tedrahendron Lett.,1974(15),8,647-650. Catellani M, Angrew. Chem. Int. Ed. 1997,36,119-122. 8 Carbopalladation of Norbornene

10. Palladacycle Formation 1.Inability of bicycle system for beta-Hybride elimination 2.Electrophilic aromatic substisution at ortho aromatic carbon 9 Sicher J. Angrew. Chem. Int. Ed. 1972,11,200-203

11. Palladacycle Formation EAS: Parshall G W. Acc Chem Res,1970(3),139-144. Markies BA. J Chem Soc Chem Commun,1992, 1420-1423. Wheland-type Intermediate rate limiting step. 10 ESA: electrophilic aromatic substitution

12. Supports ESA for deprotonation is not rate limiting. Echavarren AM.Chem Eur J. 2001(7), 2341-2345. R NO2HOMe Minutes for 50% conversation 24010010 Catellani M. J Organomet Chem,1992, 425:151 11 Palladacycle Formation

13. Oxidative addition 2 A side product ofen seen: X=Br, nd X=I, 62% Catellani M, Synthesis, 1996,769-772 12

14. 13 Addition with Alkyl Halides 1,10-phenanthroline Ligand: Catellani M, J Organomet Chem, 1993.458:C12 Lautens M. Angew Chem Int Ed,2007,1485-1488 Oxidative addition 2 80% ee63%ee

15. 14 Addition with Aryl Halides Catellani Mechanism: Echavarren Mechanism: Oxidative addition 2 Catellani M, J Organomet Chem, 1991.407:C30 Echavarren AM.J Am Chem Soc. 2006(128), 5033-5034. Low energy

16. 15 Reductive Elimination Catellani M. J Organomet Chem,1990.390:251 Not observed sp 2 -sp 3 bond formation

17. 16 sp 2 -sp 2 bond formation The Ortho Effect Reductive Elimination Catellani M. J Organomet Chem,1991.407:C30

18. 17 Norbornene Extrusion Steric factors! Characterized by NMR Lautens M.J Org Chem, 2009(74). 289-293

19. 18 Terminating Events

20. 19 Synthetic Applications

21. 20 Mizoroki-Heck Intermolecular Catellani M, Angrew. Chem. Int. Ed. 1997,36,119-122. R 3 =alkyl Mark. Lautens. Org Lett.2006,8,3939-3942.

22. 21 Lautens M. Org Lett, 2003(5). 4827 Lautens M. Synlett, 2006. 2629 Lautens M. J Org Chem, 2007(72). 775 Lautens M. Angew Chem Int Ed, 2007(46). 1485 Mizoroki-Heck Intermolecular

23. 22 Catellani M, Org Lett. 2006(8). 3967 Catellani M, Synthesis. 2008. 995 Oxyl-Micheal addition Mizoroki-Heck Intermolecular

24. 23 Lautens M (2000) Angew Chem Int Ed 39:1045 Lautens M (2001) J Org Chem 66:8127 Lautens M (2005) Tetrahedron 61:6283 Lautens M (2002) J Org Chem 67:3972 Mizoroki-Heck Intramolecular

25. 24 Lautens M.Angew Chem Int Ed. 2007(46). 1485 Lautens M.J Org Chem. 2009(74). 289 Mizoroki-Heck Intramolecular

26. 25 Catellani M. Chem Commun, 2000. 157 Catellani M. J Mol Catal A: Chem. 2003. 115 Suzuki-Miyaura

27. 26 Cassar-Sonogashira Yield promoted By KOAc,Excess alkyl halide Catellani M. J Organomet Chem. 2004. 689:3741 Copper –free! ~50%

28. 27 Lautens M. JACS. 2006,128, 14436-14437; Cyanation Lautens M. JACS. 2007,129, 15372-15372; Zn(CN)2 K4Fe(CN)6

29. Direct Arylation C-H activation of arene is difficult Catellani reaction is a powful strategy for direact arylation. Marta.Catellani. Org Lett. 2001,3611-3614. Base effect ： K2CO3&Bu4NBr >> Cs2CO3&KOAc Solvents ： DMF>>DMA>>acetontrile 28 60-94%

30. Direct Arylation Mark Lautens. JACS,2005,13148; JOC,2008,1888; OL,2006,3601 OL, 2006,2043. Mark Lautens. JOC,2008,8705; OL,2006,4827 29

31. Buchwald-Hartwig Reaction Marta Catellani. OL. 2004,4759 Mark Lautens. OL. 2007,5255 30

32. 31 Addition to C=O/C=N and C=C Bonds Catellani M. Tetrahedron Lett, 2004(45),6903-6907. Mark Lautens. AICE. 2009,1849

33. 32 Conclusions Catellani reaction is a useful and mechanistically interesting method for the polyfunctionalization of aromatic molecules.