Countercurrent Exchange and Gas Exchange 學生姓名: B9902067 曾紹庭 B9902075 黃柏翰 指導老師:周淑娥 老師 指導助教:洪偉珊 助教.
學生:洪柏楷 指導教授:于淑君 博士
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Transcript of 學生:洪柏楷 指導教授:于淑君 博士
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 / 07 / 29Department 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
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N-Heterocyclic Carbenes
NHCs are stronger σ-donor and weaker π-acceptor than the most electron rich phosphines .
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- and thermal 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
How does the life start on earth
6
Miller experiment – Water, methane, ammonia and hydrogen.
Stanley L. Miller . Science 1953, 117, 528-529.
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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.
GaMe3
N OO
R COOH
R = H, Me
THF, hexane
NO
O R
O OGa
O OGa
R NO
O
1 R = H2 R = Me
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Lewis Acid-Catalyzed Strecker Reactions 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.
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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 Reactions.
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
11
Lijin Xu, Weiping Chen Organometallics, 2000, 19, 1123-1127 .
Examples of Pd(II)-Carbene Complexes
trans-syn
NNMenBu
Br
Pd(OAC)2
THF reflux, 2h
trans-anticis-syn cis-anti
NN
NN
PdBr
Br
nBu
nBu
Me
Me NN
NN
PdBr
Br
Me
nBu
Bun
Me
N N
Pd
NN
Me
Me
nBu
nBu
N N
Pd
NN
Me
Bun
nBu
Me
BrBr BrBr
N
N
X
A: X = BrB: X = I
0.5 eq. Pd(OAC)2
DMSO, 120oC, 3h N
NPd
N
N
X
X
trans -1: X = Brtrans -2: X = I
Yuan Han, Han Vinh Huynh, Journal of Organometallic Chemistry, 2007, 692, 3606–3613.
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Examples of Pd(II)-Carbene Complexes
Yuan Han, Han Vinh Huynh, Journal of Organometallic Chemistry, 2007, 692, 3606–3613.
2 AgO2CCF3
CH3CN
NN
Pd
NN
O2CCF3
O2CCF3
cis -3
N
NPd
N
N
X
X
trans -1: X = Brtrans -2: X = I
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hmim = 1-hexyl-3-methylimidazolium
Synthesis of Palladium(Il) Carbene Complexes
NN
I
Pd(OAC)2
THF
2
90oC, 3 h
yield = 70%
Br NaI Iacetone
1
100oC, 24 h
yield = 90%
NNNN
I70oC, 8 h
yield = 95%
2
(hmim)HI
PdI2(hmim)2
3
N N
Pd
NN
II
N N
Pd
NN
II
trans-syn trans-anti
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Synthesis of Pd(Il) Carbene Complex Catalyst
CH3CN, 3 h
yield = 90%
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N N
Pd
NN
II
N N
Pd
NN
IIN
N
NN
PdO
O
CF3
O
CF3
O
AgO CF3
O
Pd(hmim)2(OOCCF3)2
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1H NMR Spectra of (hmim)HI (2), PdI2(hmim)2 (3), and Pd(hmim)2(OOCCF3)2 (4)
*CDCl3
2HH
CH3
NN
I
(hmim)HI(2)
H
H H
NN
Pd
NN
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(4)
N NH3C
Pd II
NNH3C
N NH3C
Pd II
NNCH3
trans-syn trans-anti
PdI2(hmim)2(3)
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13C NMR Spectra of (hmim)HI (2), PdI2(hmim)2 (3), and Pd(hmim)2(OOCCF3)2 (4)
*CDCl3
C
C
CNN
C
Pd
NN C
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(4)
N N
Pd II
NN
N N
Pd II
NNC
trans-syn trans-syn
PdI2(hmim)2(3)
C
C
C
NC
N
I(hmim)HI
(2)
q, 2J(C,F)= 36.0 Hz
q, 1J(C,F)= 288.0 Hz
19F NMR of Pd(hmim)2(OOCCF3)2 (4)
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F
NN
Pd
NN
O CF3
O
O CF3
O
Pd(hmim)2(OOCCF3)2(4)
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 (2), PdI2(hmim)2 (3), and Pd(hmim)2(OOCCF3)2 (4)
(hmim)HI (2)
PdI2(hmim)2 (3)
Pd(hmim)2(OOCCF3)2 (4)
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
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Single-Crystal Structure of PdI2(hmim)2 (3)
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 °
Range of Pd(II)-C1.97 ~ 2.30 Å
20Lijin Xu, Weiping Chen Organometallics, 2000, 19, 1123-1127 .
trans-syn
NNMenBu
Br
Pd(OAC)2
THF reflux, 2h
trans-anticis-syn cis-anti
NN
NN
PdBr
Br
nBu
nBu
Me
Me NN
NN
PdBr
Br
Me
nBu
Bun
Me
N N
Pd
NN
Me
Me
nBu
nBu
N N
Pd
NN
Me
Bun
nBu
Me
BrBr BrBr
N-Heterocyclic Carbene Complexes of Palladium ---- cis / trans-Isomerization
trans-anti : trans-syn = 1:1
d-CDCl3
rt, 24 h
d-CDCl3
trans-anti : trans-syn = 5:1
PdI2(hmim)2 (3) trans-syn and trans-anti Isomerization
21
rt, 12h
PdI2(hmim)2 (3) recrystalized from toluene + hexane (1:15)
PdI2(hmim)2(3)
d-CDCl3
200 NMR
50 °C, 12h
trans-anti trans-syn : trans-anti = 1:1
4.3634.3254.287
+3.952
4.3804.3624.3304.3014.285
+3.9513.935
N N
Pd II
NN
trans-syn
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Strecker Reaction
R1 R2
O
TMSCN cat.
R3 NH2 NH
R3R2
CN
R1
Jiacheng Wang, Yoichi Masui, Makoto Onaka Eur. J. Org. Chem. 2010, 1763–1771.
RCHO Me3SiCN R CN
OSiMe3
RCHO R1 NH2
NR1 R
H
cyanohydrin trimethylsilyl ether
(side product)
imine(intermediate)
Route 1
Side reaction
Me3SiCNR N
H
CN
R1
product
Noor-ul H. Khan, Santosh Agrawal . Tetrahedron Letters. 2008, 49, 640–644.
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Examples of Catalytic Strecker Reaction of Ketones
R1 Me
OTMSCN
Fe(Cp)2PF6 (5 mol %)
neat, rt, 20 min R1 NH
R2
MeNC
R1= Ph, 4-MeC6H4, 2-BrC6H4, 4-O2NC6H4, 2-Naphthyl 73-94% yield
R2 NH2
R2 = Ph, PhCH2
Thomas Mathew, Chiradeep Panja, Steevens Alconcel. PNAS. 2007,104, 3703–3706.
Jiacheng Wang, Yoichi Masui, Makoto Onaka Eur. J. Org. Chem. 2010, 1763–1771.
R1 = Ph, 4-MeOC6H4, 4-BrC6H4, 3-BrC6H4, t-BuR2 = Ph, 4-ClC6H4, 4-BrC6H4, n-Bu
63-99% yield
R1 Me
O
R2 NH2 TMSCNneat, rt, 0.75-4 h
Sn-Mont (1.9 mol %)
R1 NH
R2
CNMe
R1 Me
O
TMSCNCH2Cl2, rt, 3-7 h R1 N
H
R2
MeNC
R1 = Ph, 4-BrC6H4, 4-MeC6H4, CF3, CF2H, CH2F 75-98% yield
R2 NH2
R2 = Ph, 4-MeC6H4, 4-BrC6H4, 4-ClC6H4
Ga(OTf)3 (5 mol %)
24
Jamie Jarusiewicz, Yvonne Choe. J. Org. Chem. 2009, 74, 2873–2876.
R3 Me
OTMSCN
NHC-Pdll (3 mol %)
CH2Cl2, rt, 24 h R2 NH
R4
MeNC
R3 = 2-Naphthyl, 4-MeOC6H4, 4-BrC6H4, 4-O2NC6H4, 2-Furyl 15-92% yield
R4 NH2
R4 = Ph, PhCH2
NN
MeN
O
iPr
OCH3O
PdCl
NHC-Pdll
TMSCN R1 NH
R2R2 NH2R1 Me
O
toluene, 40oC, 24-48 h
cat. (10 mol %)
R1 = Ph, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 2-Naphthyl 79-99% yield
R2 = Ph, 4-MeOC6H4, 3-OMeC6H4, 4-BrC6H4, 4-ClC6H4
Me CN
O OP
OHO
cat.
Examples of Catalytic Strecker Reaction of Ketones
Jing Nie, Teng Wanga , Jun An Ma Org. Biomol. Chem. 2010, 8, 1399–1405.
25
H
O
H
O
Cl
CHOCHO
MeO
O H
O
S H
O
N
H
O
H
O
H
O
H
O
H
O
O O
MeOO
BrO
O
ON
O
O
MeO
NH2 NH2
NH2MeO
NH2
MeO
NH2
Me
NH2
Cl
NH
NH
O NH
NH2
Aldehyde Ketone Amine
Pd(II)-Catalyzed Strecker Reactions
NH
R3R2
CNTMSCN
cat. (3 mol %)R3 NH2
R1R1 R2
O
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Pd(hmim)2(OOCCF3)2 (4) Catalyzed Strecker Reactions
Solvent Time
(min)
Conv.
(%)
Time
(min)
Conv.
(%)
toluene 5 52 25 62
CH2Cl25 55 25 87
THF 5 5 25 53
actonitrile 5 59 25 89
neat 5 >99 25 -
H
O
TMSCNNH2 N
H
CN cat. 4 (3 mol %)
rt, solvent
Reaction Conditions : Catalyst Loading = 3 mol % ; Benzaldehyde = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol ; Sodium Sulfate = 0.7 mmol.The conversion is determined by 1H NMR.
27
EntryAldehyde
(R)Time (min)
Conv. (%)
Intermediate / Product /
Side product
1 Ph 1 >99 0/100/0
2 4-ClC6H4 1 >99 0/100/0
3 4-MeC6H4 1 >99 0/100/0
4 4-MeOC6H4 1 >99 0/100/0
5 2-furyl 1 >99 0/100/0
6 2-thienyl 1 >99 0/59/41
7 2-thienyl 1 >99 0/90/10a
8 3-pyridyl 3 >99 0/100/0
9 (E)-PhCH=CH 1 >99 0/100/0
10 butyl 1 >99 0/100/0
11 cyclohexyl 1 >99 0/100/0
12 t-butyl 1 >99 0/100/0
R H
OTMSCN R N
H
CN
NH2 no cat.
neat, rt
Reaction Conditions : Aldehyde = 0.2 mmol; Benzylamine = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.aPdI2(hmim)2 (3) as catalyst (3 mol%).
Strecker Reaction Under Catalyst-Free Conditions
28
EntryAldehyde
(R)Time(min)
Conv.(%)
Int./Product
no cat. condition
Conv.(%)
Int./Product
1 Ph 5 >99 3/97 >99 69/31
2 Ph 5 93 7/86a >99 69/31
3 4-ClC6H4 10 >99 30/70 >99 82/18
4 4-MeC6H4 2 >99 0/100 97 77/20
5 4-MeOC6H4 1 >99 0/100 97 58/39
6 2-furyl 2 >99 0/100 91 16/75
7 2-thienyl 10 97 13/84 93 77/16
8 3-pyridyl 15 97 17/80 96 69/27
9 (E)-PhCH=CH 4 >99 0/100 >99 52/48
10 cyclohexyl 1 >99 0/100 >99 0/100
R H
OTMSCN
NH2
R NH
CN cat. 3 (3 mol %)
neat, rt
Reaction Conditions : Catalyst Loading = 3 mol % ; Aldehyde = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.a Pd(hmim)2(OOCCF3)2 (4) as catalyst.
PdI2(hmim)2 (3)-Catalyzed Strecker Reactions
29
H
O
TMSCN cat. 3 (3 mol %)
neat, rt
NH
CN
RR NH2
Reaction Conditions : Catalyst Loading = 3 mol % ; Benzaldehyde = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.
PdI2(hmim)2 (3)-Catalyzed Strecker Reactions
EntryAmine
(R)Time(min)
Conv.(%)
Int./ Product/ Side product
no cat. condition
Conv.(%)
Int./ Product/
Side product
1 butyl 1 95 0/90/5 >99 0/87/13
2 cyclohexyl 1 >99 0/94/6 >99 0/88/12
3 Ph 5 >99 3/97/0 >99 69/31/0
4 4-ClC6H45 >99 0/100/0 >99 78/22/0
5 4-MeC6H45 >99 0/100/0 98 63/35/0
6 piperidine 20 92 0/77/15 91 0/62/29
7 pyrrolidine 15 97 0/89/8 90 0/86/4
8 morpholine 20 >99 0/92/8 >99 0/82/18
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EntryAldehyde
(R)Time(min)
Yield(%)
Reported Data
Time(min)
Yield(%)
Reference
1 Ph 5 97 6 96 Masui Y, Chem.Eur. J., 2010
2 4-ClC6H4 10 70 10 96 Najera C., Synthesis, 2007
3 4-MeC6H4 2 99 6 92 Masui Y, Chem.Eur. J., 2010
4 4-MeOC6H4 1 99 6 97 Masui Y, Chem.Eur. J., 2010
5 2-furyl 2 99 2 93 Masui Y, Chem.Eur. J., 2010
6 2-thienyl 10 84 20 86 Abaee M. S. , Tetrahedron Lett., 2009
7 3-pyridyl 15 80 30 83 Panja C., Synlett., 2007
8 (E)-PhCH=CH 4 99 30 81 Panja C., Synlett., 2007
9 cyclohexyl 1 99 60 86 Acosta F. C., Commun., 2009
R H
OTMSCN
NH2
R NH
CN cat. 3 (3 mol %)
neat, rt
Reaction Conditions : Catalyst Loading = 3 mol % ; Aldehyde = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.
Comparison of 3-Catalyzed Strecker Reactions with Reported Data
31
EntryAmine
(R)Time(min)
Yield(%)
Reported DataTime(min)
Yield(%)
Reference
1 butyl 1 90 6 95 Masui Y, Chem.Eur. J., 2010
2 cyclohexyl 1 94 13 90 Najera C., Synthesis, 2007
3 Ph 5 97 6 96 Masui Y, Chem.Eur. J., 2010
4 4-ClC6H4 5 99 6 90 Masui Y, Chem.Eur. J., 2010
5 4-MeC6H4 5 99 8 94 Abaee M. S. , Tetrahedron Letters, 2009
6 piperidine 20 77 20 90 Azizi N., Synthetic Communications, 2004
7 pyrrolidine 15 89 20 90 Azizi N., Synthetic Communications, 2004
8 morpholine 20 92 20 96 Desai U. V., Monatshefte fur Chemie., 2007
H
O
TMSCN cat. 3 (3 mol %)
neat, rt
NH
CN
RR NH2
Reaction Conditions : Catalyst Loading = 3 mol % ; Benzaldehyde = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.
Comparison of 3-Catalyzed Strecker Reactions with Reported Data
32
Neat Neat + 100 mg Na2SO4
Time (h)
Conv. (%) Time (h)
Conv. (%)cat. 3 cat. 4 cat. 3 cat. 4
12 - <5 12 44 <515 43 - 15 50 18 - - 18 -24 54 <5 24 48 <5
Reaction Conditions : Catalyst Loading = 3 mol % ; Acetophenone = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol .The conversion is determined by 1H NMR.
PdI2(hmim)2 (3) and Pd(hmim)2(OOCCF3)2
(4)-Catalyzed Strecker Reactions of Ketone
NH
H3C CNO
TMSCN cat. 3 or cat. 4 (3 mol%)
rt
NH2
33
Entry MWcat. 3 cat. 4
Time(s)
Conv.(%)
Time(s)
Conv.(%)
1 150
120 - 120 52160 - 160 83180 85 180 88200 91 200 86220 89 220 -
2 30030 77 30 7140 82 40 7250 72 50 -
3 450 40 72 40 694 600 40 70 40 60
Microwave-Assisted PdI2(hmim)2 (3) and Pd(hmim)2(OOCCF3)2 (4)-Catalyzed Strecker
Reaction of Ketones
Reaction Conditions : Catalyst Loading = 3 mol % ; Acetophenone = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol .
The conversion is determined by 1H NMR.
NH
H3C CNO
TMSCNcat. 3 or cat. 4 (3 mol%)NH2
2 drops (Bmim)PF6, MW
34
Microwave-Assisted PdI2(hmim)2 (3) and Pd(hmim)2(OOCCF3)2 (4)-Catalyzed Strecker Reactions
Entry R1 R2
cat.3 cat.4Time
(s)Conv.(%)
Time(s)
Conv.(%)
1 Ph 200 91 180 882 3-MeOC6H4 200 85 220 803 Ph 4-MeOC6H4 200 90 200 884 4-MeC6H4 200 92 180 885 4-ClC6H4 220 94 220 766 4-MeOC6H4 Ph 200 79 240 727
4-BrC6H4
Ph 220 83 240 688 4-MeOC6H4 200 87 180 799 Ph 220 84 240 85
10 2-naphthyl 4-MeOC6H4 200 93 220 8611 3-MeOC6H4 220 84 220 8212 2-furyl Ph 200 89 200 8213
3-pyridylPh 220 81 200 75
14 4-MeOC6H4 200 89 200 84
154′-methoxy
propiophenonePh 180 68 180 63
Reaction Conditions : Catalyst Loading = 3 mol % ; Ketone = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol; (Bmim)PF6 = 2 drops; Power = 150W.The conversion is determined by 1H NMR.
NH
R2H3C CN
TMSCN cat. 3 or cat. 4 (3 mol %)
2 drops (Bmim)PF6, MWR2 NH2
R1R1
O
35
PdI2(hmim)2 (3)-Catalyzed Strecker Reactions
Benzyl amine (pKb= 4.67) Aniline (pKb= 9.3)
Me3SiCN
Me3Si CN
H2N H2N
O
CN
OSiMe3
TMSCN
O
cat. 3 (3 mol %)
2 drops (Bmim)PF6, MW
NH2
CN
MeOTMS
TMSCN
N
O
N
cat. 3 (3 mol %)
2 drops (Bmim)PF6, MW
NH2
CN
MeOTMS
Kobayashi S.; Tsuchiya Y.; Mukaiyama T. Chemistry Letters, 1991, 537-540.
36
Entry R1 R2
cat. 3 Reported DataTime
(s)Conv.(%)
Time(h)
Conv.(%)
1 Ph 200 91 0.33 94b
2 3-MeOC6H4 200 85 24 99c
3 Ph 4-MeOC6H4 200 90 24 87c
4 4-MeC6H4 200 92 6 85a
5 4-ClC6H4 220 94 0.75 95e
6 4-MeOC6H4 Ph 200 79 1 92e
74-BrC6H4
Ph 220 83 3 95a
8 4-MeOC6H4 200 87 24 82c
9 Ph 220 84 0.33 88b
10 2-naphthyl 4-MeOC6H4 200 93 24 80c
11 3-MeOC6H4 220 84 24 86c
12 2-furyl Ph 200 89 24 83d
133-pyridyl
Ph 220 81 24 40d
14 4-MeOC6H4 200 89 24 90c
154′-methoxy
propiophenonePh 180 68 3 91e
Reaction Conditions : Catalyst Loading = 3 mol % ; Ketone = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol; (Bmim)PF6 = 2 drops; Power = 150W.
The conversion is determined by 1H NMR.a Ga(OTf)3,
bFe(Cp)2PF6, cBINOL-derived phosphoric acid, dPdII-NHC, eSn-Mont
Comparison of 3-Catalyzed Strecker Reactions with Reported Data
NH
R2H3C CN
TMSCN
cat. 3 (3 mol %)
2 drops (Bmim)PF6, MWR2 NH2 R1R1
O
37
Entry R1 R2
cat. 4 Reported DataTime
(s)Conv.(%)
Time(h)
Conv.(%)
1 Ph 180 88 0.33 94b
2 3-MeOC6H4 220 80 24 99c
3 Ph 4-MeOC6H4 200 88 24 87c
4 4-MeC6H4 180 88 6 85a
5 4-ClC6H4 220 76 0.75 95e
6 4-MeOC6H4 Ph 240 72 1 92e
74-BrC6H4
Ph 240 68 3 95a
8 4-MeOC6H4 180 79 24 82c
9 Ph 240 85 0.33 88b
10 2-naphthyl 4-MeOC6H4 220 86 24 80c
11 3-MeOC6H4 220 82 24 86c
12 2-furyl Ph 200 82 24 83d
133-pyridyl
Ph 200 75 24 40d
14 4-MeOC6H4 200 84 24 90c
154′-methoxy
propiophenonePh 180 63 3 91e
Reaction Conditions : Catalyst Loading = 3 mol % ; Ketone = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol; (Bmim)PF6 = 2 drops; Power = 150W.
The conversion is determined by 1H NMR.a Ga(OTf)3,
bFe(Cp)2PF6, cBINOL-derived phosphoric acid, dPdII-NHC, eSn-Mont
Comparison of 4-Catalyzed Strecker Reactions with Reported Data
NH
R2H3C CN
TMSCN cat. 4 (3 mol%)
2 drops (Bmim)PF6, MWR2 NH2
R1R1
O
38
Proposed Mechanism for Strecker Reaction
NN
Pd
NN
O CF3
O
O CF3
O
R1 R2
O
R NH2
H2O
NR R1
R2
NHC-Pd2+ NHC-Pd2+
NC Si
R1
R2
CNNR
Si
H2O
SiOH
NR
H R2
R1CN
N N
Pd II
NN
cat. 3 cat. 4
or
39
ConclusionsWe have successfully synthesized NHC-carbene Pd(II) complexes (3) and (4) , and characterized them by using 1H- ,13C , 19F-NMR, IR spectrocopies, as well as X-ray crystallography.
We have successfully demonstrated the highly effective activity of the Pd(II) NHC-carbene 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) NHC-carbene catalyst (3) and (4) is highly active for the Strecker reactions of ketones under microwave irradiation conditions.