1、Suzuki Reaction,Mechanism Smith: JOC 1994, 59, 8151 Biaryl synthesis Suzuki: Synlett 1992, 207-210,if R-OTf used may need to add KBr (c.f. Stille coupling),OX. ADD.,RED. ELIM.,CIS ALIGN,reaction has been conducted with a range of ligands, including bidentate ligands e.g. dppf,0,0,II,II,II,N.B. can h

2、ave axis of chirality due to hindered rotation,presence of base allows formation of atecomplex transmetallates more rapidly,TRANSMET.,X=I, Br, OTf, ( Cl ),Range of solvents have been used; DMF, toluene, DME, water,Suzuki Reaction in Synthesis,Synthesis of lavendamycin analogues Godard: J. Organomet.

3、 Chem. 1996, 517, 25-36 Aryl chloride coupling Buchwald: JACS 1999, 121, 9550,N.B. oxidative addition of Ar-I (and not Cl or F),base,biologically important pharmacophore,electron rich ligand promotes oxidative addition steric bulk enhances rate of reductive elimination,Heck Reaction,Mechanism,OX. AD

4、D.,0,0,II,II,II,II,loss of two phosphine ligands activates metal,RED. ELIM.,new alkene formed,b-hydride ELIM.(Pd & H cis),INSERTION into Pd-R bond,COORDINATION of olefin,18e-,complex still co-ordinatively unsaturated,mop up with base,(Pd & R add cis),R-X : X = Br, I, OTf, ( Cl ), R = aryl, vinyl (no

5、 b-Hs) H2C=CHR : R = H, alkyl, aryl, CN (acrylonitrile), CO2R, OR (enol ethers), OAc, NHAc,Heck Reaction,Overall Selectivity electron-poor alkenes: electron-rich alkenes: b-hydride elimination:,R group generally adds to least hindered end of double bond,E-alkene favoured (thermodynamic),Pd and H mus

6、t be cis relative to each otherthis has stereochemical implications!,R group adds to least hindered position, i.e. terminal end of d.b.,R group adds to both ends BUT good control with cyclic enol ethers/enamines: get addn of R group next to heteroatom,POOR selectivity,GOOD selectivity,Synthesis of n

7、ovel amino acids Mechanism Crisp: Tetrahedron 1992, 48, 3541,Heck Reaction in Synthesis,phosphine ligands,Pd(II) reduced in situ,Pd now co-ordinatively saturated,add R group to least hindered end of d.b.,very acidic (triflic acid) add base (K2CO3) so that acid doesnt react with product,choice of 2 p

8、rotons to remove make thermodynamically favoured E-alkene,not b-H here!,0,II,II,II,II,Heck Reaction in Synthesis,Substituted dihydrofurans Larock: Tet. Lett. 1989, 30, 2603 Asymmetric variant Pfaltz: Synthesis 1997, 1338,1. ox. addn. to Pd(0),2. co-ordination of electron-rich alkene,N.B. cant make c

9、onjugated system: no b-Hs cis due to ring,4. b-hydrideelimination (cis),no alkene migration,87% yield97% e.e.,ligand better at suppressing alkene migration than BINAP (or PPh3),achiral,chiral version of PPh3 (displaces L on Pd),5. readdition ofPd and H (cis),6. b-hydrideelimination (cis),3. cis addi

10、tion of Pd and Ar(Ar next to heteroatom),Negishi Coupling,The Negishi Coupling, published in 1977, was the first reaction that allowed the preparation of unsymmetrical biaryls in good yields. The versatile nickel- or palladium-catalyzed coupling of organozinc compounds with various halides (aryl, vi

11、nyl, benzyl, or allyl) has broad scope, and is not restricted to the formation of biaryls.,Mechanism of the Negishi Coupling,Nobel Prize in Chemistry 2005 Olefin Metathesis Awarded to: Yves Chauvin, Robert H. Grubbs, Richard R. Schrock What is the reaction?,/chemistry/laureates/2005/press.html,Metathesis a “change-your-partne