M.C. White Chem 153 Cross Coupling -84- Week of october, 2002 C-C Bond Formation Csp-Csp2 Csp -csp Bonds Csp.-Csp" Bonds R R AlkyI-Ar R Alkyl R Csp-Csp"Bonds General mechanism a paradigm shift nucleophi lic substitution at an sp hybridized Alkyl-Alkyl carbon is made routine R-M R by using transition metal R2 X=I Br, OTe, CI Classifications based on the main group metal RIR2 L. Pd(o) RIx used to transfer r2 in the transmetalation event reductive oxidative Kumada coupling Negishi Coupli elimination addition Ni(0)or pd(0) Ni(O)or Pd(o) M=MgX, Li M=Al(i-Buh d-updo Zr(cl)cp2 Stille reaction Hiyama Coupling M=SiR Suzuki reaction X-M R-MR-=aryl, vinyl, alkyl PQ(0) Pd(0) transmetalation M=BX M= Cu(in situ)
M.C. White, Chem 153 Cross Coupling -84- Week of October1, 2002 C-C Bond Formation A paradigm shift: nucleophilic substitution at an sp2 hybridized carbon is made routine by using transition metal mediated catalysis. R R R R Ar R Alkyl R Alkyl Ar Csp2-Csp2 Bonds Csp3-Csp2 Bonds R R R Csp-Csp2 Alkyl Alkyl Csp3-Csp3 Bonds Kumada Coupling Ni(0) or Pd(0) M = MgX, Li Stille Reaction Pd(0) M = SnR3 Negishi Coupling Ni(0) or Pd(0) M = Al(i-Bu)2 Zr(Cl)Cp2 ZnX Suzuki Reaction Pd(0) M = BX2 Classifications based on the main group metal used to transfer R2 in the transmetalation event. Hiyama Coupling Pd(0) M = SiR3 Sonogashira Pd(0) M = Cu (in situ) R = aryl, vinyl X = I, Br, OTf, Cl Pd(II) LnPd(0) R1-X LnPd(II) R1 X R2-M LnPd(II) R1 R2 oxidative addition transmetalation X-M R1 R2 General Mechanism reductive elimination R2= aryl, vinyl, alkyl R2-M R2 R2 Cl Cl (or Ni(II) Cl Cl )
M.C. White. Chem 153 Cross-Coupling-85 Week of october 1, 2002 Kumada pushes the frontier All the pieces of the catalytic cycle were in the literature. Transmetallation: Chatt and Shaw J. Chem. Soc. 1960 1718 Report the synthesis of alkyl and aryl nickel(lI)complexes from the corresponding nickel(ln) halides n-BuMgBr (2 eq) PPh] 2 RMgBr a PPh Br h2 0.7 mol% Meb Reductive elimination/Oxidative addition: Yamamoto JOMC amada JACS1972(94)4374 1970(24)C63. " Preparation of a phenyl-nickel complex, phenyl ( dipyridyl)nickel chloride, an olefin dimerization catalyst L_Ni RI arvi. v R-xX=CI>BpI elimination
M.C. White, Chem 153 Cross-Coupling -85- Week of October 1, 2002 Kumada pushes the frontier P Ph2 Ni(II) Ph2 P Cl Cl Cl Cl n-BuMgBr (2 eq) P Ph2 Ni(II) Ph2 P Cl Cl Cl MgBr Kumada JACS 1972 (94) 4374. 0.7 mol% 94% 0.7 mol% 80% Reductive elimination/Oxidative addition: Yamamoto JOMC 1970 (24) C63. "Preparation of a phenyl-nickel complex, phenyl (dipyridyl)nickel chloride, an olefin dimerization catalyst. N N Ni(II) Cl N N Ni(II) Cl + butane N N Ni(II) Cl N N Ni(0) Cl Transmetallation: Chatt and Shaw J. Chem. Soc. 1960 1718. Report the synthesis of alkyl and aryl nickel(II) complexes from the corresponding nickel(II) halides. Ph3P Ni(II) Br PPh3 Br 2 RMgBr Ph3P Ni(II) R PPh3 R R = R' All the pieces of the catalytic cycle were in the literature... LnNi(II) LnNi(II) R1 X LnNi(II) R1 R2 MgX2 R1 R2 R2 R2 Cl Cl R1 = aryl, vinyl L X = Cl > Br> I nNi(0) R1-X R2-MgX oxidative addition transmetalation reductive elimination R2 R = aryl, vinyl, alkyl 2-MgX
M.C. White Chem 153 Cross-Coupling -86- Week of october 1, 2002 Kumada Coupling Common Bidentate Phosphine Effect of the ligand BuMgBr (2 eq) Ligand yield dppp 100 dentate phosphine liga dppm, n=0, bis( diphenylphosphino)methane exhibit higher catalytic activity dppe, n=l, bis( diphenylphosphino)ethane than monodentate phosphines dppp, n=2, bis(diphenylphosphino propane PhaP(2eq) 84 with dppp being optimal for a dppb, 3, bis(diphenylphosphino)butane ppe halides e dmpe, bis( dimethylphosphinoJethane Reactivity of ary/ halide: 2 Unlike othe 6-coupling methods, aryl and vinyl chlorides 3l(2h) exhibit higher reactivities than dmpf, bis( dimethylphosphino)ferrocene 95(31 their br or I analogs. It Br 54(4.5h)noteworthy that even ary 80(3h) Kumada Bull. Chem. Soc. Jpn. 1976(49)1958
M.C. White, Chem 153 Cross-Coupling -86- Week of October 1, 2002 Kumada Coupling P P ( )n dppm, n=0, bis(diphenylphosphino)methane dppe, n=1, bis(diphenylphosphino)ethane dppp, n=2, bis(diphenylphosphino)propane dppb, n=3, bis(diphenylphosphino)butane P P dmpe, bis(dimethylphosphino)ethane P P Fe dmpf, bis(dimethylphosphino)ferrocene Common Bidentate Phosphines Kumada Bull. Chem. Soc. Jpn. 1976 (49) 1958. P Ni(II) P Cl Cl Cl n-BuMgBr (2 eq) 0.7 mol% R2 R2 Ligand dppp dmpf Ph3P (2eq) dppe dmpe dppb % yield 100 94 84 79 47 28 Effect of the ligand: · Bidentate phosphine ligands exhibit higher catalytic activity than monodentate phosphines with dppp being optimal for a wide range of aryl and vinyl halides. Reactivity of aryl halide: P Ni(II) P Cl Cl X n-BuMgBr (2 eq) 0.7 mol% Ph2 Ph2 X % yield F Cl Br I 31 (2h) 95 (3h) 54 (4.5h) 80 (3h) · Unlike other cross-coupling methods, aryl and vinyl chlorides exhibit higher reactivities than their Br or I analogs. It is noteworthy that even aryl fluorides undergo the nickel catalyzed cross-coupling
M.C. White Chem 153 Cross-Coupling-87- Week of octo berl. 2002 Kumada Coupling: Applications Industrial production of p-substituted styrene derivatives(Hokka Chemical Industry, Japan) . CI Mecl 0. 1 mol% Strem 2001-2003 catalog bUy t-Buo S7.6/g(very cheap) Banno JOMC 2002(653)288 Functionalization of heterocyclic halides Me3 SiCH2Mga Formation of sterically hindered biaryls Nucleophilic N-heterocyclic carbenes an used as a phosphine mimics that (unlik monodentate phosphines) donot BFA- dissociate from the metal 3 mol% imidazolium salt RMgX R=CF3 H, CH3, OCH3 H,>99% steric hinderance tolerated CH3,95% only on the Grignard OCH3,98% Herrmann ACIEE 2000(39)1602
M.C. White, Chem 153 Cross-Coupling -87- Week of October1 , 2002 Kumada Coupling: Applications P Ni(II) P Cl MgCl Cl Ph2 Ph2 t-BuO Cl t-BuO P Ni(II) P Cl Cl Ph2 Ph2 N Br P Ni(II) P Cl Cl Ph2 Ph2 S MgBr Me3SiCH2MgCl BuMgBr N S N N SiMe3 0.1 mol% · Industrial production of p-substituted styrene derivatives (Hokka Chemical Industry, Japan) Strem 2001-2003 catalog $7.6/g (very cheap) Banno JOMC 2002 (653) 288. · Functionalization of heterocyclic halides 0.5-1 mol% 78% 72% 71% · Formation of sterically hindered biaryls Kumada Tetrahedron 1982 (38) 3347. Cl R R = CF3, H, CH3, OCH3 O NiII O O O 3 mol% + 3 mol% N N BF4- N N BF4- imidazolium salt RMgX Nucleophilic N-heterocyclic carbenes are used as a phosphine mimics that (unlike monodentate phosphines) do not dissociate from the metal BrMg steric hinderance tolerated only on the Grignard + R N N BF4- R= CF3, 91% H, >99% CH3, 95% OCH3, 98% Herrmann ACIEE 2000 (39) 1602
M.C. White. Chem 153 Cross-coupling -88- Week of october 1, 2002 Pd Kumada Coupling: stereospecific transmetallation Oxidative addition to Pd(o) had been reported: Fitton Chem Comm.1968.6 The nickel catalyzed Kumada coupling is stereospecific for vinyl mono-halides(complete retention of geometric configuration) but non-stereospecific for alkenyl Grignards Phap 阝2 Ph PPh3 Memebr 96%(Z)阝 bromostyrene 96%(STilbene Palladium(0)shown to be an effective, stereospecific catalyst for cross-coupling of alkenyl halides with Grignard reagents Murahashi JOMC 1975(91)C39 Ph3 C Phap 3 mol% Me Mebr MeMel 99%E阝 bromostyrene >99%(El-stilbene 99 cis-P-bromostyrene 99% cis-stilbene Palladium(0)shown to be stereospecific for alkenyl Grignards reagents. Linstrumelle TL 1978.191 Br Mg I-C6HB Ph Phap 5 mol% Note: Nickel catalysis may involve radical pathways Kumada TL 19751719 (E)-l-iodo- Me I-octene Kumada Pure& App/. Chem. 1980(52)669 >97%,(2Z, 4E)-2, 4-undecadiene (Z)-1-propenyl-l 87% yield Note: Pd cataly sts can also transmetal late with organolithium Pd(O): Br>>CI reagents: Murahashi JOMC 2002(653)27
M.C. White, Chem 153 Cross-coupling -88- Week of October 1, 2002 Pd Kumada Coupling: stereospecific transmetallation The nickel catalyzed Kumada coupling is stereospecific for vinyl mono-halides (complete retention of geometric configuration) but non-stereospecific for alkenyl Grignards: Ph Br MeMgBr P Ni(II) P Cl Cl R2 R2 Ph Me 96% (Z)-stilbene Ph MeMgBr Ph >99% (E)-stilbene Br Me 96% (Z)-β-bromostyrene >99% (E)-β-bromostyrene P Ni(II) P Cl Cl R2 R2 BrMg Me 96% Z P Ni(II) P Cl Cl R2 R2 Br Ph Me 27% Z: 73% E Kumada TL 1975 1719. Kumada Pure & Appl. Chem. 1980 (52) 669. Oxidative addition to Pd(0) had been reported: Fitton Chem. Comm. 1968, 6. PPh3 PPh3 Pd Ph3P Ph3P I Ph3P Pd(II) Ph3P I Palladium (0) shown to be an effective, stereospecific catalyst for cross-coupling of alkenyl halides with Grignard reagents. Murahashi JOMC 1975 (91) C39. Ph Br MeMgI Ph Me 99% cis-stilbene >99% yield 99% cis-β-bromostyrene PPh3 PPh3 Pd Ph3P Ph3P Palladium (0) shown to be stereospecific for alkenyl Grignards reagents. Linstrumelle TL 1978, 191. I n-C6H13 BrMg Me 3 mol% PPh3 PPh3 Pd Ph3P Ph3P 5 mol% (E)-1-iodo- 1-octene (Z)-1-propenyl-1 magnesium bromide n-C6H13 >97%, (2Z,4E)-2,4-undecadiene 87% yield Note: Pd catalysts can also transmetallate with organolithium reagents: Murahashi JOMC 2002 (653) 27. Pd(0): I>Br>>Cl Note: Nickel catalysis may involve radical pathways