Mechanistic Studies in Copper Catalysis
Jen AllevaMay 1st 2013
Timeline of Achievements in Copper Chemistry
UllmannGoldberg
1903
Glaser, C. Ann. D. Chemie U. Pharm, 1869, 2, 137171
1869
Glaser
first cross-couplings
General Historical Overview
Timeline of Achievements in Copper Chemistry
UllmannGoldberg
1903
Ullman, F. Ber. 1903, 36, 23822384Goldberg, I. Ber. 1906, 39, 16911692
1869
Glaser
first cross-couplings
General Historical Overview
Timeline of Achievements in Copper Chemistry
UllmannGoldberg
1903
Gilman, H.; Jones, R. G.; Woods, L. A. J. Org. Chem, 1952, 17, 16301634
1923 1952
Reich Gilman
synthesis of first copperorganometallic reagents
1869
Glaser
first cross-couplings
General Historical Overview
Timeline of Achievements in Copper Chemistry
UllmannGoldberg
1903
Huisgen, R. Proc. Chem Soc., 1961, 357396
1923 1952
Reich Gilman
synthesis of first copperorganometallic reagents
1869
Glaser
first cross-couplings
Huisgen
1961
2001
Sharpless
"Click" Chemistry
General Historical Overview
Timeline of Achievements in Copper Chemistry
UllmannGoldberg
1903
Huisgen, R. Proc. Chem Soc., 1961, 357396
1923 1952
Reich Gilman
synthesis of first copperorganometallic reagents
1869
Glaser
first cross-couplings
Huisgen
1961
2001
Sharpless
"Click" Chemistry
General Historical Overview
1998
Chan-Evans-LamCu CN couplings
Copper in Cross-Coupling Reactions
Copper in Cross-Coupling Reactions
BRO OR
X
X = N, O, S
X
oxidative coupling
Chan-Evans-Lam
X
X = halide
Nu
standard cross-coupling
Ullmann-Goldberg
X
X = halide
X
oxidative coupling
"Aromatic Glaser-Hay"
Nu
HN O
O
nucleophile
Electronic Properties of Copper
CuI CuII CuIIIE1/2= 2.4VE1/2= 0.16V
* Vs. SCE in MeCN, Bratsch, S. G. J. Phys. Chem. Ref. Data 1989, 18, 121
d8, metal cationd9d10
isoelectronic withNi(0)
isoelectronic withPd(II)
Electronic Properties of Copper
CuI CuII CuIIIE1/2= 2.4VE1/2= 0.16V
* Vs. SCE in MeCN, Bratsch, S. G. J. Phys. Chem. Ref. Data 1989, 18, 121
d8, metal cationd9d10
isoelectronic withNi(0)
isoelectronic withPd(II)
forms shorter bonds than Pd
harder Lewis acidity than Pd
higher affinity for O, N ligands
smaller coordination shell can notaccomodate large ancillary ligands
Beletskaya, I. P; Cheprakov, A. V. Organometallics 2012, 31, 77537808
NNH N
H
R
CuIII
Br
Electronic Properties of Copper
CuI CuII CuIIIE1/2= 2.4VE1/2= 0.16V
* Vs. SCE in MeCN, Bratsch, S. G. J. Phys. Chem. Ref. Data 1989, 18, 121
d8, metal cationd9d10
isoelectronic withNi(0)
isoelectronic withPd(II)
forms shorter bonds than Pd
harder Lewis acidity than Pd
higher affinity for O, N ligands
smaller coordination shell can notaccomodate large ancillary ligands
highly electrophilic and unstable
potent oxidizer
requires highly stabilizing ligands
Beletskaya, I. P; Cheprakov, A. V. Organometallics 2012, 31, 77537808
Electronic Properties of Copper
CuI CuII CuIIIE1/2= 2.4VE1/2= 0.16V
* Vs. SCE in MeCN, Bratsch, S. G. J. Phys. Chem. Ref. Data 1989, 18, 121
d8, metal cationd9d10
isoelectronic withNi(0)
isoelectronic withPd(II)
forms shorter bonds than Pd
harder Lewis acidity than Pd
higher affinity for O, N ligands
smaller coordination shell can notaccomodate large ancillary ligands
highly electrophilic and unstable
potent oxidizer
requires highly stabilizing ligands
unstable towards the reversereductive elimination
can not take part in ligand exchange
requires the nucleophile to be in thecoordination sphere prior to oxidativeaddition
Beletskaya, I. P; Cheprakov, A. V. Organometallics 2012, 31, 77537808
Cross-Coupling Classifications
R1 X R2
HN
R3B ML X
R2N
R3BH
organic NHnucleophile
base
regular cross-coupling: transition metal mediated nucleophilic substitution
electrophile
R1
Cross-Coupling Classifications
R1 X R2
HN
R3B ML X
R2N
R3BH
organic NHnucleophile
base
regular cross-coupling: transition metal mediated nucleophilic substitution
electrophile
R1
Pd0/PdII
Pd0
PdIIR1 X
R1 X R2
HN
R3B
PdIIR1 N R3
R2
R2N
R3
R1BH
Cross-Coupling Classifications
R1 X R2
HN
R3B ML X
R2N
R3BH
organic NHnucleophile
base
regular cross-coupling: transition metal mediated nucleophilic substitution
electrophile
R1
Pd0/PdII CuI/CuIII
Pd0
PdIIR1 X
R1 X R2
HN
R3B
PdIIR1 N R3
R2
R2N
R3
R1BH
CuI
R2
HN
R3
CuINR3
R2
R1 X
CuIIINR3
R2
R1
R2N
R3
R1
nucleophile plays the role of ancillary ligand in CuI/CuIII
Cross-Coupling Classifications
R1 M R2
HN
R3ML M
R2N
R3M
organic NHnucleophile
oxidative cross-coupling: transition metal mediated coupling of two nucleophiles
nucleophile
R1
2e
Cross-Coupling Classifications
R1 M R2
HN
R3ML M
R2N
R3M
organic NHnucleophile
oxidative cross-coupling: transition metal mediated coupling of two nucleophiles
nucleophile
R1
PdII/PdIV
PdIIR1 M
R1 M R2
HN
R3
PdIIR1 N R3
R2
R2N
R3
R1
2e
PdII
PdIVR1 N R3
R2
O2
Cross-Coupling Classifications
R1 M R2
HN
R3ML M
R2N
R3M
organic NHnucleophile
oxidative cross-coupling: transition metal mediated coupling of two nucleophiles
nucleophile
R1
PdII/PdIV CuI/CuII/CuIII
PdIIR1 M
R1 M R2
HN
R3
PdIIR1 N R3
R2
R2N
R3
R1
CuII
R2
HN
R3CuIIN
R3
R2
R1 X
CuIINR3
R2
R1
R2N
R3
R1
2e
PdII
CuICuII
CuIIINR3
R2
R1
O2
PdIVR1 N R3
R2
O2
Cross-Coupling Classifications
R1 X R2N
R3
MLLG
R2N
R3
organic NHelectrophile
inverse or Umpolung cross-coupling: transition metal mediated electrophilic substitution
nucleophile
R1LG
nucleofugal leavinggroup
Cross-Coupling Classifications
R1 X R2N
R3
MLLG
R2N
R3
organic NHelectrophile
inverse or Umpolung cross-coupling: transition metal mediated electrophilic substitution
nucleophile
R1
Pd0/PdII
Pd0
PdIIN LG
R1 X
PdIIR1 N R3
R2
R2N
R3
R1
LG
R2N
R3
LG R3
R2
nucleofugal leavinggroup
Cross-Coupling Classifications
R1 X R2N
R3
MLLG
R2N
R3
organic NHelectrophile
inverse or Umpolung cross-coupling: transition metal mediated electrophilic substitution
nucleophile
R1
Pd0/PdII CuI/CuIII
Pd0
PdIIN LG
R1 X
PdIIR1 N R3
R2
R2N
R3
R1
CuI
CuIR1 X
CuIIINR3
R2
R1
R2N
R3
R1
LG
R2N
R3
LG R3
R2
nucleofugal leavinggroup
R2N
R3
LGR1 X
Copper in Cross-Coupling Reactions
BRO OR
X
X = N, O, S
X
oxidative coupling
Chan-Evans-Lam
X
X = halide
Nu
standard cross-coupling
Ullmann-Goldberg
X
X = halide
X
oxidative coupling
"Aromatic Glaser-Hay"
Nu
HN O
O
nucleophile
Mechanistic Studies in Copper Catalysis
Shannon Stahl Xavi Ribas Ted Cohen
Copper in Cross-Coupling Reactions
BRO OR
X
X = N, O, S
X
oxidative coupling
Chan-Evans-Lam
X
X = halide
Nu
standard cross-coupling
Ullmann-Goldberg
X
X = halide
X
oxidative coupling
"Aromatic Glaser-Hay"
Nu
HN O
O
nucleophile
Chan-Evans-Lam Couplingoxidative cross-coupling
OH
Me
BHO OH
2 equiv. Cu(OAc)2
4 mol sieves, O2EtOAc
O
Me
heteroatom boronic acid diaryl ether
Chan D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P. Tetrahedron Lett. 1998, 39, 2933.Evans, D. A.; Katz, J. L.; West, T. R. 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.
nucleophile
Chan-Evans-Lam Couplingoxidative cross-coupling
OH
Me
BHO OH
2 equiv. Cu(OAc)2
4 mol sieves, O2EtOAc
O
Me
heteroatom boronic acid diaryl ethernucleophile
CuI/CuII/CuIIICuII
R2
HN
R3CuIIN
R3
R2
R1 X
CuIINR3
R2
R1
R2N
R3
R1
CuICuII
CuIIINR3
R2
R1
