chanistic Studies in Copper Catalysis Jen Alleva May 1st 2013
Timeline of Achievements in Copper Chemistry General istorical verview first cross-couplings 1869 Ullmann Goldberg Glaser 1903 Glaser, C. Ann. D. Chemie U. Pharm, 1869, 2, 137 171
Timeline of Achievements in Copper Chemistry General istorical verview first cross-couplings 1869 Ullmann Goldberg Glaser 1903 Ullman, F. Ber. 1903, 36, 2382 2384 Goldberg, I. Ber. 1906, 39, 1691 1692
Timeline of Achievements in Copper Chemistry General istorical verview first cross-couplings Ullmann Goldberg 1869 1923 1952 Glaser 1903 eich Gilman synthesis of first copper organometallic reagents Gilman,.; Jones,. G.; Woods, L. A. J. rg. Chem, 1952, 17, 1630 1634
Timeline of Achievements in Copper Chemistry General istorical verview first cross-couplings "Click" Chemistry Ullmann Goldberg uisgen 1869 1923 1952 2001 Glaser 1903 eich Gilman 1961 Sharpless synthesis of first copper organometallic reagents uisgen,. Proc. Chem Soc., 1961, 357 396
Timeline of Achievements in Copper Chemistry General istorical verview first cross-couplings "Click" Chemistry Ullmann Goldberg uisgen 1869 1923 1952 1998 2001 Glaser 1903 eich Gilman 1961 Sharpless synthesis of first copper organometallic reagents Chan-Evans-Lam Cu C couplings uisgen,. Proc. Chem Soc., 1961, 357 396
Copper in Cross-Coupling eactions
Copper in Cross-Coupling eactions B u =,, S = halide nucleophile = halide oxidative coupling standard cross-coupling oxidative coupling u Chan-Evans-Lam Ullmann-Goldberg "Aromatic Glaser-ay"
Electronic Properties of Copper E 1/2 = 0.16V E 1/2 = 2.4V Cu I Cu II Cu III d 10 isoelectronic with i(0) d 9 d 8, metal cation isoelectronic with Pd(II) * Vs. SCE in C, Bratsch, S. G. J. Phys. Chem. ef. Data 1989, 18, 1 21
Electronic Properties of Copper E 1/2 = 0.16V E 1/2 = 2.4V Cu I Cu II Cu III d 10 isoelectronic with i(0) d 9 d 8, metal cation isoelectronic with Pd(II) forms shorter bonds than Pd harder Lewis acidity than Pd higher affinity for, ligands smaller coordination shell can not accomodate large ancillary ligands Beletskaya, I. P; Cheprakov, A. V. rganometallics 2012, 31, 7753 7808 * Vs. SCE in C, Bratsch, S. G. J. Phys. Chem. ef. Data 1989, 18, 1 21
Electronic Properties of Copper E 1/2 = 0.16V E 1/2 = 2.4V Cu I Cu II Cu III d 10 isoelectronic with i(0) d 9 d 8, metal cation isoelectronic with Pd(II) forms shorter bonds than Pd harder Lewis acidity than Pd higher affinity for, ligands smaller coordination shell can not accomodate large ancillary ligands highly electrophilic and unstable potent oxidizer requires highly stabilizing ligands Br Cu III Beletskaya, I. P; Cheprakov, A. V. rganometallics 2012, 31, 7753 7808 * Vs. SCE in C, Bratsch, S. G. J. Phys. Chem. ef. Data 1989, 18, 1 21
Electronic Properties of Copper E 1/2 = 0.16V E 1/2 = 2.4V Cu I Cu II Cu III d 10 isoelectronic with i(0) d 9 d 8, metal cation isoelectronic with Pd(II) forms shorter bonds than Pd harder Lewis acidity than Pd higher affinity for, ligands smaller coordination shell can not accomodate large ancillary ligands highly electrophilic and unstable potent oxidizer requires highly stabilizing ligands unstable towards the reverse reductive elimination can not take part in ligand exchange requires the nucleophile to be in the coordination sphere prior to oxidative addition Beletskaya, I. P; Cheprakov, A. V. rganometallics 2012, 31, 7753 7808 * Vs. SCE in C, Bratsch, S. G. J. Phys. Chem. ef. Data 1989, 18, 1 21
Cross-Coupling Classifications regular cross-coupling: transition metal mediated nucleophilic substitution 1 2 3 B M L 1 2 3 B organic electrophile nucleophile base
Cross-Coupling Classifications regular cross-coupling: transition metal mediated nucleophilic substitution 1 2 3 B M L 1 2 3 B organic electrophile nucleophile base 1 Pd II 1 2 3 B Pd 0 Pd 0 /Pd II 2 1 Pd II 3 1 2 3 B
Cross-Coupling Classifications regular cross-coupling: transition metal mediated nucleophilic substitution 1 2 3 B M L 1 2 3 B organic electrophile nucleophile base 1 Pd II 1 2 3 B 2 Cu I 2 3 3 1 Pd 0 /Pd II Cu I /Cu III Pd 0 2 1 Pd II 3 Cu I 2 3 Cu III 1 1 2 3 B 1 2 3 nucleophile plays the role of ancillary ligand in Cu I /Cu III
Cross-Coupling Classifications oxidative cross-coupling: transition metal mediated coupling of two nucleophiles 1 M organic nucleophile 2 3 M L M 2e nucleophile 1 2 3 M
Cross-Coupling Classifications oxidative cross-coupling: transition metal mediated coupling of two nucleophiles 1 M organic nucleophile 2 3 M L M 2e nucleophile 1 2 3 M 1 M Pd II 1 M 2 3 Pd II Pd II /Pd IV 2 1 Pd II 3 2 2 1 2 3 1 Pd IV 3
Cross-Coupling Classifications oxidative cross-coupling: transition metal mediated coupling of two nucleophiles 1 M organic nucleophile 2 3 M L M 2e nucleophile 1 2 3 M 1 M Pd II 1 M 2 3 2 Cu II 2 3 3 1 Pd II Pd II /Pd IV 2 1 Pd II 3 2 Cu II Cu I /Cu II /Cu III 2 3 Cu II 1 2 2 Cu I Cu II 1 2 3 1 Pd IV 3 1 2 3 2 3 Cu III 1
Cross-Coupling Classifications inverse or Umpolung cross-coupling: transition metal mediated electrophilic substitution 1 LG 2 3 M L LG 1 2 3 organic nucleophile electrophile nucleofugal leaving group
Cross-Coupling Classifications inverse or Umpolung cross-coupling: transition metal mediated electrophilic substitution 1 LG 2 3 M L LG 1 2 3 organic nucleophile electrophile nucleofugal leaving group 2 LG 2 3 3 LG Pd II 1 Pd 0 Pd 0 /Pd II 2 1 Pd II 3 1 2 3
Cross-Coupling Classifications inverse or Umpolung cross-coupling: transition metal mediated electrophilic substitution 1 LG 2 3 M L LG 1 2 3 organic nucleophile electrophile nucleofugal leaving group 2 LG 2 3 3 LG Pd II 1 1 1 Cu I LG 2 3 Pd 0 /Pd II Cu I /Cu III Pd 0 2 1 Pd II 3 Cu I 2 3 Cu III 1 1 1 2 3 2 3
Copper in Cross-Coupling eactions B u =,, S = halide nucleophile = halide oxidative coupling standard cross-coupling oxidative coupling u Chan-Evans-Lam Ullmann-Goldberg "Aromatic Glaser-ay"
chanistic Studies in Copper Catalysis Shannon Stahl avi ibas Ted Cohen
Copper in Cross-Coupling eactions B u =,, S = halide nucleophile = halide oxidative coupling standard cross-coupling oxidative coupling u Chan-Evans-Lam Ullmann-Goldberg "Aromatic Glaser-ay"
Chan-Evans-Lam Coupling oxidative cross-coupling B 2 equiv. Cu(Ac) 2 4Å mol sieves, 2 EtAc heteroatom boronic acid diaryl ether nucleophile Chan D. M. T.; Monaco, K. L.; Wang,.-P.; Winters, M. P. Tetrahedron Lett. 1998, 39, 2933. Evans, D. A.; Katz, J. L.; West, T.. Tetrahedron Lett. 1998, 39, 2937. Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan, D. T., Combs, A. Tetrahedron Lett. 1998, 39, 2941.
Chan-Evans-Lam Coupling oxidative cross-coupling B 2 equiv. Cu(Ac) 2 4Å mol sieves, 2 EtAc heteroatom boronic acid diaryl ether nucleophile 2 Cu II 2 3 3 1 Cu II Cu I /Cu II /Cu III 2 Cu II can be made catalytic with an added oxidant 2 Cu I 3 1 Cu II CEL is stoichiometric in Cu II 1 2 3 2 3 Cu III 1
Chan-Evans-Lam Coupling select catalytic methods B 20 mol% [Cu() TMEDA] 2 Cl 2 C 2 Cl 2, 2, r.t. 72% Collman, J. P.; Zhong, M. rg. Lett. 2000, 2, 1233 1236
Chan-Evans-Lam Coupling select catalytic methods B 20 mol% [Cu() TMEDA] 2 Cl 2 C 2 Cl 2, 2, r.t. 72% 2 Si() 3 1.1 equiv Cu(Ac) 2 TBAF, DMF, 2, r.t. 61% Lam, P. S.; Deudon, S.; auptman, E.; Clark, C. G. Tetrahedron Lett. 2001, 42, 2427 2429 Collman, J. P.; Zhong, M. rg. Lett. 2000, 2, 1233 1236
Chan-Evans-Lam Coupling select catalytic methods B 20 mol% [Cu() TMEDA] 2 Cl 2 C 2 Cl 2, 2, r.t. 72% 2 Si() 3 1.1 equiv Cu(Ac) 2 TBAF, DMF, 2, r.t. 61% 2 B 5 mol% Cu(Ac) 2 10 mol% myristic acid 2,6-lutidine, Ph, r.t. 91% Antilla, J. C.; Buchwald, S. L. rg Lett, 2001, 3, 2077 2079 Lam, P. S.; Deudon, S.; auptman, E.; Clark, C. G. Tetrahedron Lett. 2001, 42, 2427 2429 Collman, J. P.; Zhong, M. rg. Lett. 2000, 2, 1233 1236
Chan-Evans-Lam Coupling determining reaction stoichiometry B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Chan-Evans-Lam Coupling determining reaction stoichiometry B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% Cu and 2 stoichiometry determined from anaerobic single-turnover experiment Cu II /product ratio is 2:1 King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Chan-Evans-Lam Coupling determining reaction stoichiometry B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% Cu and 2 stoichiometry determined from anaerobic single-turnover experiment result consistent with Cu oxidase mechanism Cu II /product ratio is 2:1 Cu I / 2 ratio is 4:1 King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Chan-Evans-Lam Coupling initial rates experiment reveals turnover-limiting step B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% Initial rates experiment: suggest transmetalation as turnover-limiting King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Chan-Evans-Lam Coupling initial rates experiment reveals turnover-limiting step B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% Initial rates experiment: suggest transmetalation as turnover-limiting 1 st order dependence on Cu(Ac) 2 saturation dependence on boronic ester King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Chan-Evans-Lam Coupling initial rates experiment reveals turnover-limiting step B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% Initial rates experiment: suggest transmetalation as turnover-limiting 1 st order dependence on Cu(Ac) 2 Cu I oxidation is relatively fast compared to transmetalation saturation dependence on boronic ester 0 order dependence on 2 King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d xy d z 2 d yz d xz ground state
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d x 2 y 2 d xy d xy d z 2 d z 2 d yz d xz d yz d xz ground state coupling excited state
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d x 2 y 2 d x 2 y 2 d xy d xy d xy d z 2 d z 2 d z 2 d yz d xz d yz d xz d yz d xz ground state coupling excited state d z 2 does not couple orbitals have incorrect symmetry
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d x 2 y 2 d x 2 y 2 d xy d xy d xy d z 2 d z 2 d z 2 d yz d xz d yz d xz d yz d xz ground state coupling excited state d z 2 does not couple orbitals have incorrect symmetry g obs = g e xλ ΔE
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d x 2 y 2 d x 2 y 2 d xy d xy d xy d z 2 d z 2 d z 2 d yz d xz d yz d xz d yz d xz ground state coupling excited state d z 2 does not couple orbitals have incorrect symmetry g obs = g e xλ ΔE g obs : empirical value from spectrum g e : energy of free electron (2.00023)
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d x 2 y 2 d x 2 y 2 d xy d xy d xy d z 2 d z 2 d z 2 d yz d xz d yz d xz d yz d xz ground state coupling excited state d z 2 does not couple orbitals have incorrect symmetry g obs = g e xλ ΔE g obs : empirical value from spectrum g e : energy of free electron (2.00023) x: modification factor of the free electron based on orbital mixing
Electron Paramagnetic esonance Spectroscopy Cu II : d 9, square planar d x 2 y 2 d x 2 y 2 d x 2 y 2 d xy d xy d xy d z 2 d z 2 d z 2 d yz d xz d yz d xz d yz d xz ground state coupling excited state d z 2 does not couple orbitals have incorrect symmetry g obs = g e xλ ΔE g obs : empirical value from spectrum g e : energy of free electron (2.00023) x: modification factor of the free electron based on orbital mixing λ: spin orbit coupling constant ΔE: energy between two orbitals
Chan-Evans-Lam Coupling initial rates experiment reveals turnover-limiting step B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% EP spectroscopy shows catalyst resting state as Cu II no strong field aryl ligand evident consistent with transmetalation being as turnover-limiting reaction progress correlated with EP spectra King, A. E.; Brunold, T. C.; Stahl. S. S. J. Am. Chem. Soc. 2009, 131, 5044 5045
Chan-Evans-Lam Coupling equilibrium prior to transmetalation B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling equilibrium prior to transmetalation B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% deviation from standard conditions effect on efficiency added acetate inhibition added acetic acid inhibition Cu(Cl 4 ) 2 instead of Cu(Ac) 2 no reactivity King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling equilibrium prior to transmetalation B 5 mol% Cu(Ac) 2 1 atm 2, 27 C, 6h B() 2 () 88% 12% deviation from standard conditions effect on efficiency added acetate inhibition added acetic acid inhibition Cu(Cl 4 ) 2 instead of Cu(Ac) 2 no reactivity Cu(Cl 4 ) 2 + 1 equiv aac rate acceleration Cu(Cl 4 ) 2 + 1 equiv a rate acceleration King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling EP spectroscopy King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling EP spectroscopy EP signals appears after addition of boronic ester King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling EP spectroscopy EP signals appears after addition of boronic ester exhibits a saturation depedence on concentration of ester King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling EP spectroscopy acetic acid additive sodium acetate additive both display an inhibitory effect on EP signal suggesting that paddlewheel structure is stabilized King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling EP spectroscopy EP signal obtained immediately after mixing Cu(Ac) 2 and boronic ester displays two species King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling EP spectroscopy EP signal obtained immediately after mixing Cu(Ac) 2 and boronic ester displays two species relative concentrations of the two species are altered by the addition of additives King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of transmetalation B 1/2[Cu(Ac) 2 ] 2 Cu II (Ac) B Ac Cu II B inhibitory effect of added acetate King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of transmetalation B 1/2[Cu(Ac) 2 ] 2 Cu II (Ac) B Ac Cu II B Cu II B Cu II B Ac inhibitory effect of added acetic acid King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of transmetalation B 1/2[Cu(Ac) 2 ] 2 Cu II (Ac) B Ac Cu II B Cu II B Cu II B irreversible transmetalation Cu II Ac inhibitory effect of added acetic acid B aryl Cu(II) King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of oxidative coupling Cu(II) nucleophile coordination lowerscu II /Cu III redox potential Cu(II) Copper xidase mechanism King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of oxidative coupling Cu(II) B irreversible and turnover-limiting transmetalation nucleophile coordination lowerscu II /Cu III redox potential Cu(II) Cu(II) Copper xidase mechanism King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of oxidative coupling Cu(II) B irreversible and turnover-limiting transmetalation nucleophile coordination lowerscu II /Cu III redox potential Cu(II) Cu(II) Copper xidase mechanism Cu(II) Cu(III) Cu(I) xidation to Cu(III) stoichiometry determined from single turnover experiment King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of oxidative coupling Cu(II) B irreversible and turnover-limiting transmetalation nucleophile coordination lowerscu II /Cu III redox potential Cu(II) Cu(II) Copper xidase mechanism Cu(I) Cu(II) reductive elimination Cu(III) Cu(I) xidation to Cu(III) stoichiometry determined from single turnover experiment King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Chan-Evans-Lam Coupling mechanism of oxidative coupling Cu(II) B irreversible and turnover-limiting transmetalation nucleophile coordination lowerscu II /Cu III redox potential Cu(II) Cu(II) 2 Copper xidase stoichiometry determined from single turnover experiment 2 Cu(I) mechanism Cu(II) reductive elimination Cu(III) Cu(I) xidation to Cu(III) stoichiometry determined from single turnover experiment King, A. E.; yland, B. L.; Brunold, T. C.; Stahl, S. S. rganometallics, 2012, 31, 7948.
Copper in Cross-Coupling eactions B u =,, S = halide nucleophile = halide oxidative coupling standard cross-coupling oxidative coupling u Chan-Evans-Lam Ullmann-Goldberg "Aromatic Glaser-ay"
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle Classic Ullmann-Goldberg reaction 2 equiv. Cu I L 2 equiv. = Br, Cl, I symmetric biaryl bond
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle Classic Ullmann-Goldberg reaction 2 equiv. Cu I L 2 equiv. = Br, Cl, I symmetric biaryl bond Ullmann-type coupling u Cu I L u = Br, Cl, I C heteroatom bond
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle nucleophile coordination/ deprotonation 1 2 1 2 Cu I Cu I proposed mechanism
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle nucleophile coordination/ deprotonation 1 2 Cu I reversible oxidative addition 1 2 proposed mechanism Cu I 1 CuIII 2
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle nucleophile coordination/ deprotonation 1 2 Cu I reversible oxidative addition 1 2 proposed mechanism Cu I 1 CuIII 2 reductive elimination 1 2
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle 1 2 CuIII putative aryl Cu III Cu III has been widely proposed as an intermediate oxidative addition product has never been observed oxidative addition to Cu has no precedent
Ullmann-Goldberg eaction cross-coupling reaction mediated by Cu I /Cu III redox cycle 1 2 CuIII putative aryl Cu III utilization of constraining macrocyclic ligands UV-Vis spectroscopy (M, CV, -ray) kinetics
Ullmann-Goldberg eaction kinetics reveal reversible oxidative addition 2 CuTf, aq. 3 2 2 Br acetone 2 Cohen, T.; Cristea, I. J. Am. Chem. Soc. 1976, 98, 748 753
Ullmann-Goldberg eaction kinetics reveal reversible oxidative addition 2 CuTf, aq. 3 2 2 Br acetone 2 formation of 2, 2'-dinitro-biphenyl: formation of nitrobenzene: 2 CuTf 2 CuTf Br Br 2 nd order dependence 1 st order 1 st order 1 st order Cohen, T.; Cristea, I. J. Am. Chem. Soc. 1976, 98, 748 753
Ullmann-Goldberg eaction kinetics reveal reversible oxidative addition 2 CuTf, aq. 3 2 2 Br acetone 2 2 k 1 2 Cu Tf Cu III Br Br k 1 2 2 Cu III Br k 2 2 Br 2 Cohen, T.; Cristea, I. J. Am. Chem. Soc. 1976, 98, 748 753
Ullmann-type Coupling eaction direction observation of Cu I /Cu III redox steps ibas and Stahl's strategy: x Cu Cu III Cu I macrocyclic ligand shown to undergo C insertion with Cu highly constrained and stabilized aryl Cu III species Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction direction observation of Cu I /Cu III redox steps ibas and Stahl's strategy: x Cu Cu III Cu I macrocyclic ligand shown to undergo C insertion with Cu highly constrained and stabilized aryl Cu III species allows for characterization by 1 M, CV and UV-Vis allows for study of reductive elmination Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction direction observation of Cu I /Cu III redox steps ibas and Stahl's strategy: Cu I Cu III x Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction direction observation of Cu I /Cu III redox steps ibas and Stahl's strategy: Cu I Cu III x allows for study of oxidative addition allows for study of mechanism of C bond formation Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction characterization of aryl-cu III complex CuCl 2 or CuBr 2 Cu III x CuCl or CuBr Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction characterization of aryl-cu III complex CuCl 2 or CuBr 2 Cu III x CuCl or CuBr Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction characterization of aryl-cu III complex CuCl 2 or CuBr 2 Cu III x CuCl or CuBr electronic spectra (LMCT): agrees with ligand field strengths of the halides 369 and 521 nm 399 and 550 nm 422 and 635 nm Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction characterization of aryl-cu III complex CuCl 2 or CuBr 2 Cu III x CuCl or CuBr cyclic voltammetry: values for Cu III /Cu II redox couple 330mV 310mV 300mV Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction reductive elimination CuCl 2 Cu III x Tf (1.5-10 equiv) C, 298K <1hr Cl quantitative Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction reductive elimination CuCl 2 Cu III x Tf (1.5-10 equiv) C, 298K <1hr Cl quantitative Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction reductive elimination CuCl 2 Cu III x Tf (1.5-10 equiv) C, 298K <1hr Cl quantitative E 1/2 (mv) k obs (S 1 ) (298K) complex x Cl 330 7.12(6)x10-2 Cu III Br Cl 300 400 4.08(5)x10-4 5.05(5)x10-3 rate of reductive elimination controlled by C halogen bond strength C reductive elimination rates do not correlate with E 1/2 values Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction reductive elimination -pyr Cu III Br Br Br 3.3 mol% Cu(C) 4 PF 6 CD 3 C, 298K -pyr Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction relationship of this study to the Ullmann reaction Br 3.3 mol% Cu(C) 4 PF 6 CD 3 C, 298K -pyr 2 Cu I 2 3 3 1 Cu I /Cu III Cu I 2 3 Cu III 1 1 2 3 Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction relationship of this study to the Ullmann reaction Br 3.3 mol% Cu(C) 4 PF 6 CD 3 C, 298K -pyr 2 Cu I 2 3 3 1 macrocyclic ligand lowers barrier to oxidative addition macrocyclic ligand stabilizes Cu III Cu I /Cu III *effectively inverts the relative rates of both redox steps Cu I 2 3 Cu III 1 1 2 3 Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Ullmann-type Coupling eaction relationship of this study to the Ullmann reaction Br 3.3 mol% Cu(C) 4 PF 6 CD 3 C, 298K -pyr 2 Cu I 2 3 3 1 macrocyclic ligand lowers barrier to oxidative addition macrocyclic ligand stabilizes Cu III Cu I /Cu III *effectively inverts the relative rates of both redox steps Cu I 2 3 Cu III 1 mechanism of Ullmann-Goldberg can vary *use of less coordinating nucleophiles or higher coordinate ligands can affect key redox steps 1 2 3 Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; ibas,. Chem Sci. 2010, 1, 326 330
Copper in Cross-Coupling eactions B u =,, S = halide nucleophile = halide oxidative coupling standard cross-coupling oxidative coupling u Chan-Evans-Lam Ullmann-Goldberg "Aromatic Glaser-ay"
Glaser-ay Type Couplings oxidative cross-coupling xidative coupling of a Cu-bound nucleophile and a C bond Cu 2 2 Z 2 Z amada, T; Ye,.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833 835
Glaser-ay Type Couplings oxidative cross-coupling xidative coupling of a Cu-bound nucleophile and a C bond Cu 2 2 Z 2 Z Cu II Cu III Cu I amada, T; Ye,.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833 835 Brasche, G.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 1932 1934 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling xidative coupling of a Cu-bound nucleophile and a C bond Cu 2 2 Z 2 Z Ar Cu 2 Ar =, Li Cu = Cl, Br 2 amada, T; Ye,.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833 835 Brasche, G.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 1932 1934 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling xidative coupling of a Cu-bound nucleophile and a C bond Cu 2 2 Z 2 Z Ar Cu 2 Ar =, Li Cu = Cl, Br 2 amada, T; Ye,.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833 835 Brasche, G.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 1932 1934 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling Li = Cl, Br Cu 2 2 equiv. Cu 2 Ac Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling Li = Cl, Br Cu 2 2 equiv. Cu 2 Ac Cu(Ac) 2 Cu(Tf) 2 Cu(Cl 4 ) 2 CuF 2 CuCl 2 CuBr 2 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling Li = Cl, Br Cu 2 2 equiv. Cu 2 Cl Cl Ac Cl Cu(Ac) 2 70% 7% Cu(Tf) 2 Cu(Cl 4 ) 2 CuF 2 CuCl 2 CuBr 2 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings preliminary investigations Li = Cl, Br Cu 2 LiBr 25 mol% CuBr 2 Br Ac, 60 C Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings preliminary investigations Li = Cl, Br Cu 2 LiBr 25 mol% CuBr 2 Br Ac, 60 C LiCl 25 mol% CuCl 2 Cl 6 equiv. Ac, 100 C Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings preliminary investigations Li = Cl, Br Cu 2 LiBr 25 mol% CuBr 2 Br Ac, 60 C Δ CuBr 2 2 CuBr Br 2 regioselectivity follows that of electrophilic aromatic bromination Barnes, J. C.; ume, D.. Inorg. Chem. 1963, 2, 445 448 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings preliminary investigations Li = Cl, Br Cu 2 20 mol% a 2 1.3 equiv Br Br Δ CuBr 2 2 CuBr Br 2 regioselectivity follows that of electrophilic aromatic bromination Zhang, G.; Liu,.; u, Q.; Ma, L.; Liang,. Adv. Synth. Catal. 2006, 346, 862 866 Barnes, J. C.; ume, D.. Inorg. Chem. 1963, 2, 445 448 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings preliminary investigations Li = Cl, Br Cu 2 25 mol% CuBr 2 Br Ac, 2, LiBr Br 75% Δ CuBr 2 2 CuBr Br 2 regioselectivity follows that of electrophilic aromatic bromination Zhang, G.; Liu,.; u, Q.; Ma, L.; Liang,. Adv. Synth. Catal. 2006, 346, 862 866 Barnes, J. C.; ume, D.. Inorg. Chem. 1963, 2, 445 448 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling xidative coupling of a Cu-bound nucleophile and a C bond Cu 2 2 Z 2 Z Ar Cu 2 Ar =, Li Cu = Cl, Br 2 amada, T; Ye,.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833 835 Brasche, G.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 1932 1934 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings oxidative cross-coupling xidative coupling of a Cu-bound nucleophile and a C bond Cu 2 2 Z 2 Z Ar Cu 2 Ar =, Li Cu = Cl, Br 2 amada, T; Ye,.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833 835 Brasche, G.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 1932 1934 Yang, L.; Lu, Z.; Stahl, S. S. Chem Commun, 2009, 6460 6462
Glaser-ay Type Couplings evidence for an aryl-cu III King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings evidence for an aryl-cu III CuBr 2 Br C Cu III Br Cu I King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings evidence for an aryl-cu III CuBr 2 Br C Cu III Br Cu I Cu III Br C King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings evidence for an aryl-cu III CuBr 2 Br C Cu III Br Cu I Cu III Br C Br Cu III C pyr King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings kinetics of methoxylation reaction using the method of intial rates Cu III Br C kinetics determined by 2 consumption King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings kinetics of methoxylation reaction using the method of intial rates Cu III Br C arene ligand (mm) Cu II (mm) p 2 (torr) 1 st order dependence 1 st order dependence 0 order dependence King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings kinetics of methoxylation reaction using the method of intial rates Cu III Br C arene ligand (mm) Cu II (mm) p 2 (torr) 1 st order dependence 1 st order dependence 0 order dependence catalytic steps involving 2 are comparatively fast Cu reoxidation is not rate-determining King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings kinetics of methoxylation reaction using the method of intial rates Cu III Br C 1 M complicated due to paramagnetic line broadening indicates that Cu II is formed during reaction King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings kinetics of methoxylation reaction using the method of intial rates Cu III Br C Cu III Cu II King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings kinetics of methoxylation reaction using the method of intial rates Cu III Br C Cu III Cu II King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings proposed mechanism of Aromatic Glaser-ay coupling Cu II Cu II King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings proposed mechanism of Aromatic Glaser-ay coupling Cu II Cu I Br Cu II Cu III King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings proposed mechanism of Aromatic Glaser-ay coupling Cu II Cu I Br Cu II Cu III 2 2 Cu I King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Glaser-ay Type Couplings proposed mechanism of Aromatic Glaser-ay coupling Cu II Cu I Br accounts for apparent build-up of Cu II during reaction Cu II Cu III 2 2 Cu I King, A. E.; uffman, L. M.; Casitas, A.; Costas, M.; ibas,.; Stahl, S. S. J. Am Chem. Soc, 2010, 1147 1169
Copper in Cross-Coupling eactions B u =,, S = halide nucleophile = halide oxidative coupling standard cross-coupling oxidative coupling u Chan-Evans-Lam Ullmann-Goldberg "Aromatic Glaser-ay"
Copper in Cross-Coupling eactions