化 学 系 Department of Chemistry Catellani Reaction

Introduction Mechanism Synthetic Applications Contents Conclusions 1

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

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 , Postdoc, UC, Prof. J. Halpern , short periods in Sheffied,Tsukuba,Russia and China present, full professor at Uiversity of Parma. Catellani M, Angrew. Chem. Int. Ed. 1997,36, Introduction 3

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

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

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

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

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

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,

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

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

Oxidative addition 2 A side product ofen seen: X=Br, nd X=I, 62% Catellani M, Synthesis, 1996,

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

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

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

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

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

18 Terminating Events

19 Synthetic Applications

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

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

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

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

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

25 Catellani M. Chem Commun, Catellani M. J Mol Catal A: Chem Suzuki-Miyaura

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

27 Lautens M. JACS. 2006,128, ; Cyanation Lautens M. JACS. 2007,129, ; Zn(CN)2 K4Fe(CN)6

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

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

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

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

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