高三化学中国国家集训队上课课件2Organometallic(I).ppt

Lecture: Palladium-Catalyzed Complexity Generating Reactions,Outline Organo-transition Metal Chemistry Transition metal-catalyzed Reaction Mechanisms Heck Reaction Heck Cascade Stille/Suzuki Coupling Reaction Allylic Alkylation Reaction Reference Mitchell. T.N. Synthesis, 1992, 803 Stille. J. K. ACIEE. 1986, 25, 508 Pure and applied chemistry 1994, 66, 213 Tetrahedron-Asymmetry 1992, 3, 1089,更多资源,Organo-transition Metal Chemistry,Chemistry involves intermediates containing transition-metal carbon bonds,Electron Counting,Formal neutral ligand (L): PR3, NR3, CO, alkyne, Alkene Formal anionic ligand (X): R, Ar, H, X, CN, RCO,ML4 Pd(0) d10 = 10 e PPh3 2 e X 4 = 8 e 18 e ML2 Pd(0) d10 = 10 e PPh3 2 e X 2 = 4 e 14 e ML2X2 Pd(II) d8 = 8 e Ar, I 2 e, 2 e = 4 e PPh3 2 e X 2 = 4 e 16 e,Ligand Exchange,Ligand Association and Ligand Dissociation Ligand dissociation is usually the first step in pre-catalyst activation,Oxidative Addition/Reductive Elimination,Ligand effect - electron donating ligands facilitate oxidative addition (e.g. PR3, R, H) - electron withdrawing ligands facilitate reductive elimination (e.g., CO, CN, olefins),Migratory Insertion/De-insertion,Migration of the one ligand to a neighboring unsaturated ligand (CO, RNC, alkyne, alkene), generating a vacant site Usually reversible Vacant site is cis to the newly formed ligand,Carbometallation/-elimination,Carbometallation: Insertion into alkene/alkyne group Migrating aptitude of -Eliminaton : H Alkyl, Ar RCO OR -Hydride Elimination : Very common pathway for the decomposition of alkylmetal complexes,General Mechanism,In situ reduction of Pd(II) to Pd(0),Beletskaya, Chem. Rev. 2000, 100, 3009,Classifications based on the main group metal used to transfer R2 in the transmetalation event.,Heck Reaction,General Reference about Pd-catalyzed Reactions Metal catalyzed Cross-coupling Reactions, Diederich, F. and Stang, P. J., Eds.; Wiley-VCH: New York, 1998 Heck Reaction A.d.Meijere et al, Angew. Chem. Int. Ed. 1994, 33. 2379 B. M. Trost et al, Angew. Chem. Int. Ed. 1995, 34. 259 E. Negishi et al, Chem. Rev. 1996, 96, 365 W. Cabri et al, Acc. Chem. Res. 1995, 28, 2,Overview of Heck Reaction,R1: Aryl, Vinyl, Benzylic, Allylic, Acyl X: N2+ I BrOSO2CF3 Cl (relative rate of oxidative addition) PdX Pd(0) or Pd(II) Active Pd(0) species can be instantaneously made from Pd(II) in reaction media Base : Scavenger of HX PR3: Prevents Pd(0) from precipitation to make palladium mirror Solvent: Often coordinating solvents such as NMP, DMA, DMF, acetonitrile but sometimes toluene can be used Temperature: r.t. to 140 oC,Catalytic Cycle of Heck Reaction,Intramolecular Heck Cascade,Subsequent carbopalladation should be faster than termination process of the former carbopalladation intermediate (e.g. dehydropalldation),Programming Heck Cascade,Programmed substrate: Alkyne or 1,1-dialkylalkene groups are positioned three to five carbon apart leading to the formation of 5,6, and 7-membered rings,Tandem Heck Reaction,Intermolecular Heck reaction followed by intramolecular one Syn-Carbopalladation leads to only one geometric isomer,E. Negish. et al. J. Org. Chem. 1989, 54, 2507,Tandem Heck Reaction,B. M. Trost et al. J. Am. Chem. Soc 1992, 114, 9836,Intermolecular Heck reaction terminated with intramolecular one,Sequential Tandem Heck Reaction,L. Tietze et al. J. Am. Chem. Soc. 1998, 120, 8971,Two Heck reactions are achieved in one-pot,Stable Neopentyl Organo-Pd-intermediate,L. E. Overman et al J. Am. Chem. Soc. 1999, 121, 5467,Strained tricyclic system,Stable Organo-Pd Intermediates,Intermediate organo-palladium species are thermally stable due to the absence of hydrogen -syn to palladium,Chemistry of Stable Organo-Pd Intermediate An Opportunity for Diversification,Catalytic role: Regeneration of catalytic Pd species,Stille Coupling Reaction,R1, R2 : sp2-hybridized carbon X: I OSO2CF3 Br Cl Aptitude for tansmetalation: alkynyl alkenyl benzyl, allyl alkyl Exceptional functional group tolerance High cost and toxicity of organotin reagent,Suzuki Coupling Reaction,Less expensive, less toxic alternative to Stille coupling Sp3 carbon can be involved in coupling partner Relative rates of reductive elimination aryl-aryl alkyl -aryl alkyl-alkyl Somewhat basic conditions needed,Catalytic Cycle of Stille/Suzuki Coupling,Transmetallation step is supposed to be slowest in Stille coupling Depending on the leaving group, oxidative addition can be a rate determining step in Suzuki coupling,Tandem Heck-Stille Reaction,Three different Pd-catalyzed reactions (Heck, Stille, Sonogashira reaction) are used Selective functionalization of gem-dibromide,S. Torri et al Tet. Lett. 1993, 34, 2139,Sequential Tandem Heck-Suzuki Reaction,Three component coupling reaction on solid support Stoichiometric amount of Pd used,J. A. Ellman. et al J. Org. Chem. 1996, 61, 4494,Termination with Carbonylation,Higher affinity and fast insertion of CO ligand to Pd (Sometimes even faster than dehydropalladation) Relative migratory insertion rate alkyne carbon monoxide (ca. 1 atm) alkene,Heck-Carbonylation and Intramolecular Nucleophilic Addition,E. Negishi et al. J. Am. Chem. Soc. 1994, 116, 7923,Heck-Carbonylation and intermolecular Nucleophilic addition,Three component coupling reaction,F. Voeglte. et al “Stimulating concepts in Chemistry” pp 56,Pd-catalyzed Allylic Alkylation,General reactivty of substrate ; Halide, Carbonate Acetate epoxide (?) Nucleophile : C-nucleophile- malonate, active methylene nucleophile : Heteroatom (N, O, S, P, Si)-based nucleophile : Hydride (B-H, Sn-H, Al-H and formates) : Organometallics (Zn-R, Zr-R, Sn-R etc.) Soft Nucleophile (pKa 25) is known to attack ligand directly,Catalytic Cycle of Pd-catalyzed Allylic Alkylation,Active cationic form of 3- allyl Pd comple