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1
Synthesis and Characterization of N-Heterocyclic Carbene Palladium(II) Complexes. The Catalytic
Application on Strecker Synthesis of α-aminonitriles
學生:洪柏楷 指導教授:于淑君 博士
2010 / 05 / 17Department of Chemistry & Biochemistry
Chung Cheng University
2
Phosphine Ligand
Phosphines are electronically and sterically tunable.
Expensive.
Air/water sensitive and thermally unstable.
Metal leaching.
Chemical waste - water bloom.
P P PPO
OO
P(Bu)3 P(OiPr)3 P(Me)3 P(o-tolyl)3
25 mL 211.5 USD
25 G 396 USD
100 mL 31.9 USD
10G 135.5USD
3
N-Heterocyclic Carbenes
NHCs are stronger σ-donor and weaker π-acceptor than the most electron rich phosphine .
NHCs can be useful spectator ligands, because they are sterically and electronically tunable.
NHCs can promote a wide series of catalytic reactions like phosphine.
NHCs have advantages over phosphines and offer catalysts with better air-stability.
[M]
4
N-Heterocyclic Carbenes as Ligands- In the early 90's NHC were found to have bonding properties similar to trialklyphosphanes and alkylphosphinates.
- compatible with both high and low oxidation state metals
- examples:
- reaction employing NHC's as ligands:
Herrmann, W. Angew. Chem. Int. Ed. 2002, 41, 1290-1309.
Herrmann, W. A.; Öfele, K; Elison, M.; Kühn, F. E.; Roesky, P. W. J. Organomet. Chem. 1994, 480, C7-C9.
N NMe Me
W
COCOOCCOOC V
NHCCHN
NHCCHNCl
ClTi ClCl
ClCl
NN
N N
Me Me
MeMe
Re OO
OMe
N NMe Me Ru
PCy3
Ph
NNMesMes
ClCl
C-H Activation of Methane
Oxidation of Alcohols
Reductive Aldol Reaction
Allylation of Aldehydes
Strecker Reaction
5
The Catalytic Applications of Pd(II)
Heck reaction
Suzuki–Miyaura Reaction
Carbon-Surfur Coupling Reactions
Buchwald-Hartwig Reactions
Etherification Reaction
Ethylene-CO copolymerization Reaction
6
Strecker Amino Acid Synthesis
The Strecker amino acid synthesis is a series of chemical reactions that synthesize an amino acid from an aldehyde (or ketone).
Adolph Strecker was the first to understand this organic reaction at 1850.
Two novel organogallium(III) complexes were tested in vitro against human tumour.
R1
O
HH2N
R2 NaCN
AcOH
HNR2
R1 CN
H+ HNR2
R1 CO2H
Santiago Gomez-Ruiz , Milena R. Journal of Organometallic Chemistry 2009,694, 2191–2197.
Strecker, D. Ann.Chem. Pharm. 1850,75, 27-45.
The Various Modes of α-Aminonitrile Reactivity
7Enders, D.; Shilvock, J. P. Chem. Soc. Rev. 2000, 29, 359-373.
8
Lewis Acid-Catalyzed Strecker Reaction Lewis acid catalysts Et3N 、 InCl3 、 Ga(OTf)3 、 BiCl3
Paraskar, A. S.; Sudalai, A. Tetrahedron Lett. 2006, 47, 5759-5762. Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2002, 58, 2529-2532. Surya Prakash, G. K.; Mathew, T. ; Panja, C.; Alconcel, S.; Vaghoo, H.; Do, C.; Olah, G. A. PNAS 2007, 104, 3703-3706. De, S. K. ; Gibbs, R. A. Tetrahedron Lett. 2004, 45, 7407-7408.
Transition metal Lewis acid catalysts RuCl3 、 NiCl2 、 Sc(OTf)3 、 Cu(OTf)2
De, S. K. Synth. Commun. 2005, 35, 653-656. De, S. K. J. Mol. Catal. A: Chem. 2005, 225, 169-171.
Lanthanide Lewis acid catalysts Pr(OTf)3 、 La(O-i-Pr) 、 Yb(OTf)3
De, S. K. Synth. Commun. 2005, 35, 961-966.
Others KSF 、 I2
Yadav, J. S.; Subba Reddy, B. V.; Eeshwaraiah B.; Srinivas, M. Tetrahedron 2004, 60, 1767-1771. Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595-4597.
9
Motivation
Using NHCs ligand to replace phosphine ligand in organomatallic catalysis.
Synthesis of NHC-Pd(II) complexes with well-defined structures.
Developing a practical and effective process for theStrecker Reaction.
Greener catalysis –solventless and microwave conditions.
10Toshikazu Hirao, Kenji Tsubata . Tetrahedron Letters 1978 , 18, 1535 - 1538.
Pd(II)Cl2(RNC)2 NH2CHCH(OC2H5)2R1 R2
PdCl
Cl
CNHR
NHCHCH(OC2H5)2
R1 R2
NHR
H -2C2H5OH
PdCl
Cl
CN
N
NHRR2
R1
R
H
24 h
rt
The First Palladium(II) Carbene Complexes
11Lijin Xu, Weiping, Chen, Journal of Organometallic Chemistry, 2000, 598, 409–416.
Lijin Xu, Weiping Chen Organometallics, 2000,19, 1123-1127 .
Examples of Pd(II)-Carbene Complexes
12
Examples of Pd(II)-Carbene Complexes
Yuan Han, Han Vinh Huynh, Journal of Organometallic Chemistry, 2007, 692, 3606–3613.
13
hmim = 1-hexyl-3-methylimidazolium
Synthesis of Palladium(Il) Carbene Complexes
BrNaI
acetone reflux, 24 hI
NN
NN
I70oC, 8 h
(hmim)HI(1)
yield = 90 % yield = 95 %
N N
Pd II
NN
trans-syn
N N
Pd II
NN
trans-syn
PdI2(hmim)2(2)
NN
I
(hmim)HI(1)
Pd(OAC)2
THF reflux, 3h
yield = 70%
14
Synthesis of Pd(Il) Carbene Complex Catalyst
N N
Pd II
NN
trans-syn
CH3CN, 3h
yield = 90%
NN
Pd
NN
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(3)
AgO CF3
O
N N
Pd II
NN
trans-syn
PdI2(hmim)2(2)
15
1H NMR Spectra of(Hmim)HI (1),PdI2(hmim)2 (2),and Pd(hmim)2(OOCCF3)2 (3)
*CDCl3
2HH
NN
Pd
NN
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(3)
CH3
NN
I
(hmim)HI(1)
H
H H
N NH3C
Pd II
NNH3C
N NH3C
Pd II
NNCH3
trans-syn trans-syn
PdI2(hmim)2(2)
16
13C NMR Spectra of (Hmim)HI (1), PdI2(hmim)2 (2), and Pd(hmim)2(OOCCF3)2 (3)
*CDCl3
NC
N
I(hmim)HI
(1)
C
C
C
N N
Pd II
NN
N N
Pd II
NNC
trans-syn trans-syn
PdI2(hmim)2(2)
C
C
C
NN
C
Pd
NN C
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(3)
19F NMR of Pd(hmim)2(OOCCF3)2 (3)
17
NN
Pd
NN
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(3)
F
4000 3500 3000 2500 2000 1500 1000 50040
45
50
55
60
65
70
75
80
85
90
95
100
tran
smitt
ance
(a.
u.)
wavenumber(cm-1)18
IR Spectra of (Hmim)HI (1), PdI2(hmim)2 (2), and Pd(hmim)2(OOCCF3)2 (3)
(Hmim)HI (1)
PdI2(hmim)2 (2)
Pd(hmim)2(OOCCF3)2 (3)
1868(C=O)
1166
1219
imidazole H–C–C & H–C–N bending
2953,2930,2857 1569
imidazole ring ν (C–H) aliphatic ν (C–H)
imidazole ν (ring stretching)
3079,3140
2954, 2928, 28573113, 3149
2957, 2933, 28613133, 3162
1566
1576
1190
19
Single-Crystal Structure of PdI2(hmim)2 (2)
bond lengths [Å] bond angles [deg]
Pd(1)-C(11)Pd(1)-I(1)
2.019(5)2.6066(5)
N(4)-C(11)-N(3)C(11)-Pd(1)-C(1) I(2)-Pd(1)-I(1)C(11)-Pd(1)-I(2)C(1)-Pd(1)-I(1)
105.0(5)179.8(2)179.22(2)89.62(15)90.27(14)
Pd(2)-C(21) Pd(2)-I(3)#1
2.032(6)2.6059(6)
N(5)-C(21)-N(6)C(21)-Pd(2)-C(21)#1I(3)-Pd(2)-I(3)#1C(21)-Pd(2)-I(3)#1C(21)#1-Pd(2)-I(3)
105.4(5)180.0(4)180.00(2)90.0(2)90.0(2)
dihedral angle8.20 °
20
Bond lengths [Å]Pd(1)-C(1) 2.024(5)Pd(1)-I(1) 2.6066(5)N(1)-C(1) 1.352(7)N(1)-C(2) 1.387(7)C(2)-C(3) 1.341(8)
Bond angles [deg]C(1)-Pd(1)-I(1) 90.27(14)C(11)-Pd(1)-C(1) 179.8(2)I(2)-Pd(1)-I(1) 179.22(2)N(2)-C(1)-N(1) 105.2(4)C(1)-N(1)-C(2) 110.6(4)C(3)-C(2)-N(1) 107.0(5)
Selective Bond lengths and Bond Angles of PdI2(hmim)2 (2)
Lijin Xu, Weiping, Chen, Journal of Organometallic Chemistry, 2000, 598, 409–416.
21
N-Heterocyclic Carbene Complexes of palladium ---- Isolation of cis and trans Isomers
Dieter Enders, Heike Gielen. Chem. Ber, 1996, 129, 1483–1488.
trans-anti could be dissolved in Et2O. trans-syn was not soluble in Et2O.
cis (yield : 8 %) + trans (yield : 82%) trans-syn : trans-anti = 1: 2.6
22
N-Heterocyclic Carbene Complexes of Palladium ---- cis / trans-isomerization
cis(white solid)Yield : 19 %
trans(Yellow solid)Yield : 55 %
1H NMR(trans-syn )4.06 (s, 6H, NCH3)4.44 (t ,4H, NCH2 )Lijin Xu, Weiping Chen Organometallics, 2000,19, 1123-1127 .
1H NMR(trans-anti) 4.09 (s, 6H, NCH3)4.46 (t ,4H, NCH2 )
trans-anti : trans-syn =1:1
d-CDCl3
Rt ,24 htrans-anti : trans-syn =5:1
PdI2(hmim)2 (2) trans-syn and trans-anti isomerization
23
Rt ,12h
PdI2(hmim)2 (2) recrystalized from toluene + hexane (1:15)
PdI2(hmim)2(2)
d-CDCl3
200 NMR
50 °C,12h
trans-anti trans-syn + trans-anti
4.3634.3254.287
+3.952
4.3804.3624.3304.3014.285
+3.9513.935
N N
Pd II
NN
trans-syn
24
NHC-Pd(II) Complex-Catalyzed Strecker Reaction
Entry 1~14TOF(h-1) = 1.38
Jamie Jarusiewicz, Yvonne Choe. J. Org. Chem. 2009, 74, 2873–2876.
a Reaction condition: 3 mol % Pd catalyst , 0.2 mmol benzaldehyde, 0.2 mmol aniline,0.4 mmol TMSCN, sodium sulfate 0.7 mmol, room temperature stirring in 1 mL of CH2Cl2 b Isolated yield.
25
a Reaction condition: 3 mol % Pd catalyst , 0.2 mmol benzaldehyde, 0.2 mmol aniline,0.4 mmol TMSCN, sodium sulfate 0.7 mmol, room temperature stirring in 1 mL of CH2Cl2 b Isolated yield.
Jamie Jarusiewicz, Yvonne Choe. J. Org. Chem. 2009, 74, 2873–2876.
TOF (h-1) 1.18
0.68
0.80
0.86
0.94
TOF (h-1) 1.38
1.19
1.31
0.23
0.61
NHC-Pd(II) Complex-Catalyzed Strecker Reaction
26
Strecker Reaction Catalyzed by K2PdCl4
B. Karmakar, J. Banerji. Tetrahedron Letters. 2010, xx, xxx–xxx.
a Reaction condition: 1.0 mmol aldehyde, 1.0 mmol aniline, 1.3 mmol TMSCN, 10 mol % K2PdCl4, room temperature stirring.b Isolated yield.
TOF (h-1) 50
20
20
20
10
14.2
10
10
TOF (h-1) 20
20
20
10
10
8.3
10
10
13.3
Noor-ul H. Khan, Santosh Agrawal . Tetrahedron Letters. 2008,49, 640–644.
27
Fe(Cp)2PF6 Catalyzed Strecker Reaction
a Reaction condition: 5 mol % Fe(Cp)2PF6 , 1 mmol aldehyde or ketone , 1 mmol aniline and1.3mmol TMSCN, reaction time 20 min.b isolated yields.
TOF (h-1) 56.4
55.2
49.2
51.6
48.6
54
53.4
TOF (h-1) 56.4
51
51.6
49.2
40.8
50.4
52.2
Fe(Cp)2PF6 Catalyzed Strecker Reaction
28
Noor-ul H. Khan, Santosh Agrawal . Tetrahedron Letters. 2008,49, 640–644.
29
Proposed Mechanism for the Strecker Reaction
30
Pd(Hmim)2(OOCCF3)2 (3) Catalyzed Strecker Reaction
Reaction condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline 0.4 mmol TMSCN, sodium sulfate 0.7 mmol, 0.2 mL solvent , RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
Solvent TimeConv.(%)
TOF(h-1)
TimeConv.(%)
TOF(h-1)
toluene
5 min
52 208
25 min
62 49.6
CH2Cl2 55 220 87 69.6
THF 5 20 53 42.4
CH3CN 59 236 89 71.2
neat >99 400 -
31
AldehydeTime(min)
Conv.(%)
TOF(h-1)
AldehydeTime(min)
Conv.(%)
TOF(h-1)
3 >99 666 15 97 130
20 80 80 15 90 120
2 >99 1000 5 >99 400
5 >99 400
H
O
H
O
Cl
CHO
CHO
MeO
N
H
O
H
O
H
O
R H
OTMSCN
3 mol % cat.(3)
Neat, RT
NH2
R NH
CN
Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction
32
AldehydeTime(min)
Conv.(%)
TOF(h-1)
AldehydeTime(min)
Conv.(%)
TOF(h-1)
1 >99 2000 1 >99 2000
1>99
2000 1>99
2000
1>99
2000 1>99
2000
Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction-(1)
H
O
H
O
Cl
CHO
CHO
MeO
R H
OTMSCN
3 mol % cat.(3)
Neat, RT
NC
R
HNNH2
O H
O
S H
O
Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline 0.4 mmol TMSCN, RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
33
AldehydeTime(min)
Conv.(%)
TOF(h-1)
AldehydeTime(min)
Conv.(%)
TOF(h-1)
1 >99 2000
1>99
2000 1>99
2000
1>99
2000
H
O
R H
OTMSCN
3 mol % cat.(3)
Neat, RT
NC
R
HNNH2
N
H
O
H
O
H
O
H
O
Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction-(2)
34
AmineTime(min)
Conv.(%)
TOF(h-1)
AmineTime(min)
Conv.(%)
TOF(h-1)
3 >99 666 5 95 380
5 >99 400 5 99 400
5 >99 400
5 90 360
H
O
TMSCN3 mol % cat.(3)
Neat, RT NHR
RNH2NC
NH2
NH2
NH2
NH
NH
O NH
Condition: 0.2 mmol benzaldehyde, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction
35
Pd(Hmim)2(OOCCF3)2 (3)-Catalyzed Strecker Reaction
NH
H3C CNO
TMSCN3 mol % cat.(3)
Neat, RT
RNH2
Condition: 0.2 mmol acetophenone, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
1 2 14 24
Neat +100 mgSodium Sulfate
< 5 % < 5 % 65 % 99 %
Neat < 5 % < 5 % < 5 % < 5 %
Time (h)
TOF(h-1)1.38
36
Pd(Hmim)2(OOCCF3)2 (3) Catalyzed Strecker Reaction under Microwave Irradiation Conditions
Condition: 0.2 mmol acetophenone, 0.2 mmol aniline, 0.4 mmol TMSCN, RT, 3 mol % Pd (Hmim)2(OOCCF3)2 . The conversion is determined by 1H NMR.
30 40 60 80
2 drops - 41% - -
4 drops 43 % 30 % 60 % 31%
8 drops - 40 % - -
40 60 70 80
1 drop 56 % 71 % 72 % 58 %
2 drops 42 % - - -
4 drops 27 % - - -
Time (sec)
Time (sec)
(bmim)HPF6
(bmim)HPF6
600 w
450 w
TOF(h-1)1420
NH
H3C CNO
TMSCN3 mol % cat.(3)
Microwave
RNH2
37
ConclusionsWe have successfully synthesized NHC-carbene Pd(II) complexes (2) and (3) , and characterized them by using 1H- ,13C , 19F-NMR, IR spectrocopies.
We have successfully demonstrated the highly effective activity
of the Pd(II) complex catalyst towards the Strecker reactions.
Not many successful synthetic protocols for Strecker reactions of ketones has been reported. We have demonstrated in this
study that our target Pd(II) carbene catalyst (3) is highly active for theStrecker reactions of ketones.
The Strecker reactions of ketones can be further accelerated under microwave irradiation conditions.