1 Synthesis and Characterization of N- Heterocyclic Carbene Copper(I) Complexes. The Catalytic...
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Transcript of 1 Synthesis and Characterization of N- Heterocyclic Carbene Copper(I) Complexes. The Catalytic...
1
Synthesis and Characterization of N-Heterocyclic Carbene Copper(I) Complexes.
The Catalytic Application on Huisgen Cycloaddition and Acetylation Reactions.
學生 : 李岳峰
指導教授 : 于淑君 博士
日期 : 2014. 7. 8 國立中正大學化學暨生物化學系
2
NN
Cu
N N
OTf
NNMes
Cu
N NMes
OTf
R OH Ac2O ROAc60 ¢J , neat (or 300 W, neat)
+ Cat. (2 mol%)
R1 N3 + R2
Cat. (1 mol%)
rt, neat
N
N
N
R1
R2
Acetylation of alocohol reaction
Huisgen cycloaddition reaction
Catalyst
[Cu(bmim)2](OTf) [Cu(Mesbim)2](OTf)
Outline
2
CV, XPS
3
Organometallic Catalyst
aSteven P. Nolan et al. Organometallics. 2004, 23, 1157.
Entry NHC HX‧ Time (h) Conv. (%)
1 no ligand 24 00
2 02 99
O
CuCl (3 mol%), NaOtBu (20 mol%)
NHC¡EHX (3 mol%), toluene, r.t.Et3SiH +
OSiEt3
NN
iPr
iPr BF4
iPr
iPr
3
Organometallic catalyst vs. inorganic salta
+ Metal Ligand Organometallic Catalyst
4
Choice of LigandReported – Phosphines were used as ligand of transition metals, such as Cu, Ni, Pd, Pt, Rh, Mn et al.a,b
aR. B. King et al. Inorg. Chem. 1971, 10, 1841.bVenkataraman, D. et al. Org. Lett. 2001, 3, 4315.
ex: Ni(CO)(PMe3)3 Pd(PPh3)4 Pt(PPh3)4 RhCl(PPh3)3
Entry R1 X Time (h) Yield (%)
1 H I 06 78
2 H Br 36 73
3 H Cl 36 49
Phosphines ligands enhance formation of C─N bondsb
4
N
H
+
R1
X Cu(neocup)(PPh3)Br (10 mol%)
KOtBu, toluene, 110 ¢JN
R1
5
Drawbacks – Air sensitive
P─C 、 P─OR bond were unstable at high temperaturesb
Metal leaching
Environmental pollution ─ eutrophication
Advantage – Strong σ-donating and good -accepting abilitya
Electronically and sterically tunable
PC6F5
C6F5
C6F5 P
OiPrOiPr P
o-tolyl
o-tolylo-tolylOiPr
aHerrmann, W. et al. Angew. Chem. Int. Ed. 1997, 36, 2162.bQuin, L. D. A Guide to Organophosphorus Chemistry, 2000. 5
6
N-Heterocyclic Carbenes
NNR R NNR R
N
NNR R
:
cyclic diaminocarbenes
imidazol-2-ylidenes
1,2,4-triazole-3-ylidenes
: :
NHCs PR3
the ability of -acceptinga weak strong
the ability of σ-donatinga stronger strong
the ability of oxidantionb hard easy
electronically and sterically tunable good good
environmental pollution – eutrophication
LigandProperty
The property of ligand between NHCs and PR3
aHerrmann, W. A. et al. Angew. Chem. Int. Ed. 1997, 36, 2162.bSong, W. et al. Angew. Chem. Int. Ed. 2003, 42, 892. 6
7
Choice of Metal
Price – Copper is a relatively cheaper transition metal.
The consumption and recovery of copper in the worlda
2006 2007 2008 2009 2010 2011
copper consumption (kt) 22753 23906 23841 22664 24538 25003
copper recycling (kt) 08332 08448 08611 07435 08442 08643
the percentage of copper recycling (%)
00037 00035 00036 00033 00034 00035
CuCl2 ScCl3 PdCl2 ReCl3 AgCl YbCl3 GdCl3
LD50 (mg/kg)
584 314 0200 0280 1500 300 0378
Acute toxicity
aThe International Copper Study Group 7
8
The Catalytic Applications of Cu
•O-arylation of phenols
•Diels-Alder reactions
•Acetylation of alcohols
•Asymmetric addition of dialkylzinc to imines
Cu(II)
Cu(I)•O-arylation of phenols
•Hydrosilylation of ketones
•Epoxidation reaction
•Substitution reaction
•Kharasch-Sosnovsky reaction (allylic oxidations of olefins) 8
•Oxidation of alcohols
•C─X bond formation (X = C, O, S, N)
•Friedel-Crafts alkylation reactions
•Oxidation of alcohols
•C─X bond formation (X = C, O, S, N)
•Reductive aldol reaction
•Huisgen cycloaddition
9
Acetylation of Alcohol
Application : 1. protective agent
2. medicine synthesis, ex: aspirin
3. protein acetylation
Reported apporaches :
(1) Lewis basea
aQingmin Wang et al. Org. Lett. 2014, 16, 236
O OH
OH
O OH
O
O
Ac2O
aspirinsalicylic acid
OH
Ac2O, toluene, rt, 6 h
DMAP (5 mol%)OAc
98 %
DMAP = 4-(N,N-Dimethylamino)pyridine
9
10
OH
Ac2O, CH2Cl2, rt, 0.5 h
Cu(OTf)2 (2.5 mol%)OAc
97 %
(3) Metal triflatesb
aJaved Iqbal et al. J. Org. Chem. 1992, 57, 2001bK. L. Chandra et al. Tetrahedron, 2002, 58, 1369
(2) Lewis acida
OH
Ac2O, CH3CN, 80 ¢J , 2 h
CoCl2 (5 mol%)OAc
95 %
10
[Cu(bmim)2](OTf) and [Cu(Mesbim)2](OTf) may be the first CuI complexes to catalyze acetylation of alcohol reactions.
11
Huisgen Cycloaddition
Application : 1. dye 2. photosensitive material 3. UV resistance
(1) Reduction of CuII salta
O+
sodium ascorbate, 5 mol%
H2O/BuOH, 2:1, rt, 8h
NN
NON3
CuSO4¡E5H2O, 1 mol%
91 %
aK. Barry Sharpless et al. Angew. Chem. Int. Ed. 2002, 41, 2596bFokin, V. V. et al. Org. Lett. 2004, 6, 2853
+ 1 mol % Cu(CH3CN)4PF6
H2O/t-BuOH = 1:2, rt, 24h
NN
N
84 %
N N
N BnN
3
1 mol %
N3
(2) Ligand assisted CuI saltb
11
Reported apporaches :
12
(4) NHC-CuI b
aAlonso, F. et al. Eur. J. Org. Chem. 2010, 1875.bDíez-González, S. et al. Eur. J. 2006, 12, 7558.
N3 +N
NN(SIMes)CuBr, 0.8 mol%
neat, rt, 0.3 h
98 %
+10 mol % Cu NPs
THF, 65 oC,10 min
NN
N
98 %
N3
(3) Nanosized, activated Cu(0) powdera
12
[Cu(bmim)2](OTf) 、 [Cu(Mesbim)2](OTf) Cat, (1 mol%)
neat, rt, 0.17 h>99 %
13
NHC Cu(OTf)2+ (NHC)Cu(II) complexexpected
13
Organometallic Catalyst
+ Metal Ligand + Metal Ligand + Metal Ligand + Metal Ligand
The Design of Organometallic Catalyst
However …The products are (NHC)Cu(I)─structure determined by XPS 、ESI-Mass and 1H NMR. Catalytic application : (1) acetylation of alcohols (2) Huisgen cycloaddition.
14
Motivation
1. Based on economic and conservation of environment standpoint, we use copper metal as the metal center of organometallic catalyst
2. To avoid metal leaching, we use NHC ligands to replace phosphine ligands in organometallic catalyst
3. Synthesis of NHC-CuI complexes with well defined structures
4. Using the NHC-CuI complexes to catalyze acetylation of alcohols and Huisgen cycloaddition reactions
14
15
Preparation of Copper(I) Complex Catalysts
15
Br +NN 60 ¢J / 16 hr NN
Brneat
Yield : 95 %
Preparation of (bmim)HBr
Preparation of [Cu(bmim)2](OTf)
NNBr
+ Cu(OTf)2
t-BuONa, CH3CN
r.t. / 4 hr NN
Cu
N N
OTf
Yield : 60 %
2 eq 1 eq
6 eq
1616
Preparation of 1-mesityl-1H-imidazole
Preparation of [Cu(Mesbim)2](OTf)
NNMes
OO
NH2
+
1. HCHO / NH4OAc / HOAc / H2O 70 oC / 18 hr
2. NaHCO3 / H2O, 1 hr
NN Mes
Br + Cu(OTf)2
t-BuONa, CH3CN
r.t. / 4 hr NNMes
Cu
N NMes
OTf
Yield : 55 %Preparation of (Mesbim)HBr
NN Mes + Br
CH3CN
82 oC / 24 hr
NNMes
Br
Yield : 92 %
Yield : 61 %
2 eq 1 eq
6 eq
1717
1H NMR Spectra of (bmim)HBr and [Cu(bmim)2](OTf)
NN
Cu
N N
OTf
H1
H2
H3
NN
Br
H1
H2
H3
H4 H4
(bmim)HBr
[Cu(bmim)2](OTf)
*
*#
* CHCl3
# H2O
1818
13C NMR Spectra of (bmim)HBr and [Cu(bmim)2](OTf)
NN
Br
NN
Cu
N N
OTf
C1
C1
C2
C2
(bmim)HBr
[Cu(bmim)2](OTf)
* CDCl3
*
1919
1H NMR Spectra of (Mesbim)HBr and [Cu(Mesbim)2](OTf)
NN
Br
H1
H2
H3
H4
(Mesbim)HBr
H5
H6
[Cu(Mesbim)2](OTf)
NNMes
Cu
N NMes
OTf
2020
13C NMR Spectra of (Mesbim)HBr and [Cu(Mesbim)2](OTf)
NN
Br
C1
(Mesbim)HBr
[Cu(Mesbim)2](OTf)
NNMes
Cu
N NMes
OTf
2121
IR Spectra of (bmim)HBr and [Cu(bmim)2](OTf)
NNBr
NN
Cu
N N
OTf
1226 cm-1
(H─C─C & H─C─N bending)
1169 cm-1 (H─C─C & H─C─N bending)
(bmim)HBr
[Cu(bmim)2] (OTf)
Cu(OTf)2
2222
IR Spectra of (Mesbim)HBr and [Cu(Mesbim)2](OTf)
NNMes
(Mesbim)HBr
Br
(Mesbim)HBr
NNMes
[Cu(Mesbim)2](OTf)
Cu
N N MesOTf
[Cu(Mesbim)2](OTf)
Cu(OTf)2
1201 cm-1 (H─C─C & H─C─N bending)
1226 cm-1 (H─C─C & H─C─N bending)
2323
[Cu(bmim)2](OTf) (mol/mg) [Cu(Mesbim)2](OTf) (mol/mg)
Calculated (Cu : L = 1:1)
2.85 * 10-6 2.19 * 10-6
Calculated( Cu : L = 1:2)
2.05 * 10-6 1.44 * 10-6
Experimental 1.86 * 10-6 1.31 * 10-6
NN
Cu
N N
OTf
Atomic Absorption Spectral Data of [Cu(bmim)2](OTf) and [Cu(Mesbim)2](OTf)
NNMes
Cu
N N Mes
OTf
2727
CuI (2p3/2) : 932 ~ 935 Va
CuII (2p3/2) : 935 ~ 938 V
X-Ray Photoelectron Spectral of [Cu(Mesbim)2](OTf) and Cu(OTf)2
aFrost, D. C. et al. Mol. Phys. 1972, 24, 861.
932 V
935 V
[Cu(Mesbim)2](OTf)
Cu(OTf)2 satellite
satellite
2828
Cyclic Voltammetry of [Cu(Mesbim)2](OTf)
0.805 V (oxidation peak)
NNMes
Cu
N N Mes
OTf
Reporteda
aKieltsch, I. et al. Organometallics 2010, 29, 1451.
NN
Cu
X = CH3, 0.65 V (oxidation peak) CF3, 1.24 V (oxidation peak)
X
29
2Cu(OtBu)2 + 4NaOTf2Cu(OtBu)2 2Cu(OtBu) + tBuO¢wOtBu
4(bmim)HBr 4bmim (NHC carbene) + 4NaBr + 4HOtBu
4bmim (NHC carbene ) + 2Cu(OtBu) 2[Cu(bmim)2][OtBu]
2[Cu(bmim)2][OtBu] + 2NaOTf 2[Cu(bmim)2][OTf] + 2NaOtBu
4NaOtBu2Cu(OTf)2
4NaOtBu
¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w¢w2Cu(OTf)2 + 6NaOtBu + 4(bmim)HBr 2[Cu(bmim)2][OTf] + tBuO¢wOtBu
+ 4NaBr + 2Na(OTf) + 4HOtBu
Copper reduction
(1)
(2)
(3)
29
Cu O +O O
2CuO O2
150 ¢J thermodynamic stability
Reporteda
aTsuda, T. et al. J. Am. Chem. Soc. 1972, 94, 658.
Reduction Mechanism from CuII to CuI
2
2
Proposed mechanism for catalyst synthesis
3030
R OH Ac2O ROAc60 ℃, 3 hr, neat+
Cat. (2 mol%)
EntryAlcohol or
Phenol
[Cu(bmim)2](OTf) [Cu(Mesbim)2](OTf)
Yield (%) Yield (%)
1 98 99
2 98 99
3 92 95
4 97 98
5 59 60
6 35 42
OH
OH
OH
HO
HO
OH
5
NHC-CuI Catalyzed Acetylation Reactions of ROH with Acetic Anhydride
3131
EntryAlcohol or
Phenol
[Cu(bmim)2](OTf) [Cu(Mesbim)2](OTf)
Yield (%) Yield (%)
7 97 95
8 98 99
9 97 96
10 99 99
11 99 99
12 98 97
13 92 95
R OH Ac2O ROAc60 ℃, 3 hr, neat+
Cat. (2 mol%)
OH
OHMeO
O2NOH
OH
OH
I
OH
OH
3232
Entry Alcohol or Phenol[Cu(bmim)2](OTf)
Yield (%)
1 90
2 93
3 95
4 92
5 90
6 93
OH
OH
OH
I
OH
O2NOH
OHMeO
OH
R
+ Ac2OCat. (2 mol%)
60 ¢J, 1.5 hr, neat
OAc
R
333333
Entry Alcohol or Phenol[Cu(Mesbim)2](OTf)
Yield (%)
1 75
2 77
3 85
4 77
5 74
6 66
OH
OH
OH
I
OH
O2NOH
OHMeO
OH
R
+ Ac2OCat. (2 mol%)
60 ¢J , 1 hr, neat
OAc
R
3434
R O R
O O
R O R
O OMn+
R'OHMn+
PhCH3
R O
OR'
R = MeMn+ = Na+
Reported Mechanisms for Acetylation of Alcohols
Mechanism (i)a
Mechanism (ii)b
aWack, H. et al. Org. Lett. 1999, 1, 1985.bK. L. Chandra et al. Tetrahedron, 2002, 58, 1369.
ROAc + HOAcROH
Cu(OTf)2AcOTf + Cu(OTf)OAc
detectable
Ac2O
3535
Proposed Mechanism for Acetylation of Alcohols
[Cu(bmim)2](OTf)Ac2O
O
O O
L2Cu
O
O O
L2Cu
OTf
O
L2Cu
TfO
O
O ROH
R OH
O
L2Cu
TfOO
RH
O O
AcOH + ROAc
OTf
3636
Convection transition
Thermal vs. Microwave Heating
Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250.
microwave thermal
3737
HO
NHC-CuI Catalyzed Acetylation Reactions of ROH with Acetic Anhydride under MW Irradiation
R OH Ac2O ROAc+Cat. (2 mol%)
60 ¢J or MW (300 W)
EntryAlcohol or
Phenol
[Cu(bmim)2](OTf) [Cu(Mesbim)2](OTf)
Thermal (3 h)
MW (30 s)
Thermal(3 h)
MW (30 s)
Yield (%) Yield (%) Yield (%) Yield (%)
1 98 99 99 99
2 98 99 99 99
3 92 89 95 96
4 97 97 98 99
5 59 94 60 82
6 35 65 42 61
OH
OH
5
OH
HO
OH
3838
EntryAlcohol or
Phenol
[Cu(bmim)2](OTf) [Cu(Mesbim)2](OTf)
Thermal (3 h)
MW (30 s)
Thermal(3 h)
MW (30 s)
Yield (%) Yield (%) Yield (%) Yield (%)
7 97 93 95 95
8 98 99 99 99
9 97 97 96 99
10 99 99 99 99
11 99 99 99 99
12 98 99 97 98
13 92 97 95 97OH
OHMeO
O2NOH
OH
OH
I
OH
OH
R OH Ac2O ROAc+Cat. (2 mol%)
60 ¢J or MW (300 W)
39
EntryCatalyst
Cat Conc.(mol %)
MW (W)
Time (min)
Yield(%)
1A PPTS (Pyridinium p-toluenesulfonate)
100 700 3 94a
2B NaOH 12.5 530 4 96b
3 [Cu(bmim)2](OTf) (2) 2 300 0.5 97c
4[Cu(Mesbim)2](OTf)
(5) 2 300 0.5 97c
Reaction condition :a alcohol : Ac2O (1 : 1.5), solvent = neat, b alcohol : Ac2O (1 : 2),
solvent = neat, c alcohol : Ac2O (1 : 8), solvent = neat.
OH Ac2O OAc
neat
Reported
AJong Chan Lee et al. Bull. Korean Chem. Soc. 2004, 25, 1295. BPatnam, R et al. Journal of Chemical Research 2002, 301.
39
4040
NHC-CuI Catalyzed Huisgen Cycloaddition
R1 N3 + R[Cu(bmim)2](OTf) (1 mol%)
rt, neat
N
N
N
R1
N3
N3
Entry Azide
Time (min) Yield (%) Time (h) Yield (%)
1 10 >99 1.5 >99
2 10 >99 1.5 >99
3 10 >99 1.5 >99
4 10 >99 1.5 >99
5 10 >99 1.0 >99N3
Br
N3
N3
4141
N3
N3
Entry AzideT
(℃)Time (min)
Yield (%)
T(℃)
Time (h)
Yield (%)
1 rt 10 >99rt 1.5 >41
50 1.0 >99
2 rt 10 >99 50 1.0 >99
3 rt 10 >99 50 1.0 >99
4 rt 10 >99 50 1.0 >99
5 rt 10 >99 50 0.5 >99N3
Br
N3
N3
R1 N3 + R[Cu(Mesbim)2](OTf) (1 mol%)
neat
N
N
N
R1
4242
Mechanism for Huisgen Cycloaddition
[Cu(bmim)2](OTf)PhH
(bmim)Cu Ph
(bmim)Cu Ph
NN
NBn
NN
N
Ph
Bn
Cubmim
(bmim)Cu
NN
NBn
Ph
NN
NBn
Ph
(bmim)HOTf
(bmim)HOTf
BnN3
pKa : 19
pKa : 25
4343
Conclusions
1. We have successfully synthesized [Cu(bmim)2](OTf) and [Cu(Mesbim)2](OTf) complexes. Their structures were characterized
by using 1H- and 13C-NMR, IR, AAS, XPS, ESI-Mass and CV spectroscopy.
2. We have successfully demonstrated the catalytic activity of [Cu(bmim)2](OTf) and [Cu(Mesbim)2](OTf) on the acetylation of
alcohol and Huisgen cycloaddition reactions.
3. Further acceleration on the rate of the [Cu(bmim)2](OTf)─and [Cu(Mesbim)2](OTf)─catalyzed acetylation of alcohols can be achieved under microwave irradiation conditions.