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Transcript of 1 Microwave Assisted Organomolybdenum Lewis Acid Catalyzed Mukaiyama Aldol Reactions Student :...
1
Microwave Assisted Organomolybdenum Lewis Acid Catalyzed Mukaiyama Aldol Reactions
Student : Wanchen Lee
Supervisor : Prof. Shuchun Joyce Yu
2005 / 07 / 28
Department of Chemistry & Biochemistry
Chung Cheng University
2
Mukaiyama Reaction
OSi(CH3)3 OSi(CH3)3
C C C CH2
H3C
(H3C)3SiO
C6H5
H(H3C)3SiO
C6H5
(C6H5CH2)2CO C6H5CHO
(CH3)2CO (CH3)2CHCHO
Silyl enol ether Ketone or Aldehyde
Mukaiyama, T. et. al. Chem. Lett. 1973, 1011-1014
TiCl4 H2O(H3C)3SiO
R1
R2
R3C
O
R4 R5 C
O
R1 CR2R3 CR4R5
OH
3
Lewis Acid Catalyzed Mukaiyama ReactionsI. Traditional Lewis Acids
BF3O(Et)2 、 AlCl3 、 InCl3 、 SnCl4 、 TiCl4 、 FeCl3 、 ZSM-5
II. Organometallic Lewis Acids
a. Early Transition Metals: Sc (III) 、 V(IV) 、 W(0)
O
OV OL
L
L = N-Meim
Chen, C.T. et. al. Synlett. 1999, 816-818
NN N
H
W
ON NO
2SbF6
2+
Loh, T. P. et. al. Chem. Commun. 1996, 1819-1820
Saigo, K. et. al. Chem. Lett. 1974, 323-326
Kobayashi, S. et. al. Tetrahedron Lett. 1997,
26, 4559-4562
1-methyl imidazole
Mukaiyama, T. et. al. Chem. Lett. 1973, 1011-1014
Sasidharan, M. et. al. Chem. Lett. 2003, 32, 624-625Takeshi, O. et. al. Tetrahedron Lett. 2002, 43, 8959-8962
4
b. Late Transition Metals: Fe (II) 、 Ru (II) 、 Cu (II)
PF6Fe
PPh2PPh2
O
NRu
O
N
OH2
NO
[Ru(salen)(NO)H2O] +
Cu(OTf)2
N
O
RN
O
R
Chem. Commun. 1992, 1634 Bosnich, B. et. al. Tetrahedron Lett. 1992,
39, 5729-5732
Kobayashi, S. et. al. Tetrahedron 1999, 55, 8739-8746
N
O
N
O
Cu(DS)2
DS = dodecyl sulfate (3OSOC12H25)
Kobayashi, S. et. al. Green Chem. 1999, 4, 175-177
5
III. Lanthanide Metal Triflate (OTf) Complexes :
Yb (III) 、 La (III) 、 Pr (III) 、 Nd (III) 、
Sm (III) 、 Eu (III) 、 Gd (III) 、 Dy (III) 、
Ho (III) 、 Er (III)
Kobayashi, S. et. al. J. Org. Chem. 1994, 13, 3590-3596
Kobayashi, S. et. al. Tetrahedron Lett. 1997, 26, 4559-4562
6
IV. Non-Metallic Catalysts
a. PS-Formamide
b. Ionic liquids
c. Brønsted acid ex: citric acid and benzolic acid d. Lewis base ex: lithium acetate 、 potassium acetate and sodium acetate
Ogawa, C.; Sugiura, M.; Kobayashi, S. Chem. Commun. 2003, 192-193
Chen, S. L.; Ji, S. J.; Loh, T. P. Tetrahedron Lett. 2004, 375-377
Li, G. L.; Zhao, G. J. Org. Chem. 2005, 70, 4272-4278
Mukaiyama, T.; Kawano, Y.; Fujisawa, H. Chem. Lett. 2005, 34, 88-89
N H
O
N N ( )n
X-
n=3 to 7
X= Cl, BF4, PF6
7
Solvent Systems for Mukaiyama Reactions
II. Mixed Solvent System
EtOH-H2O、 THF-H2O
I. Molecular Organic Solvents
CH2Cl2 、 CH3NO2 、 CH3CN 、 DMF
III. Green Solvents
R.T. Ionic Liquids (BmimPF6)
Water
8
N
CHO
OSiMe3
Ph InCl3 (20 mol%)
23 oC, H2O, 15 hr, 96% yield
PhOH
N
O
Indium Trichloride Catalyzed Mukaiyama Aldol Reaction in Water
Loh, T. P. et. al. Chem. Commun. 1996, 1819-1820
9
OSiMe3 H
O
Sc(OTf)3 (0.1eq)/ SDS(0.2 eq)
R.T., H2O, 4 hr, 88% yield
OHO
SDS = sodium dodecylsulfate (Na2C12H25SO4)
Sc(OTf)3-Catalyzed Aqueous Aldol Reaction in Micellar Systems
Kobayashi, S. et. al. Tetrahedron Lett. 1997, 26, 4559-4562
10
H
O
O2NOSi(CH3)3
OC2H5 CH2Cl2, -20oC, 6-12 hr
91 % yield
OH
O2N
OC2H5
O
Oxovanadium(IV) Biphenolate Catalyzed Mukaiyama Aldol Reaction
Chen, C.T. et. al. Synlett. 1999, 816-818
O
OV OL
L
10 mol% L = 1-methyl imidazole
11
H
O
Me
Me OSiMe3
OMe
[Ru(salen)(NO)H2O]+
25 oC,CD3NO2, < 3 min, 90% yield
MeO
O
PhH
Me Me
OSiMe3
1 mol%
O
NRu
O
N
OH2
NO
[Ru(salen)(NO)H2O] +
[Ru(salen)(NO)H2O]SbF6 Catalyzed Mukaiyama Aldol Reaction
Bosnich, B. et. al. Tetrahedron Lett. 1992, 39, 5729-5732
12
H
O
OSiMe3
C11H23CO2H
H2O, 23 oC, 20 hr, 75% yield
ET
OOH
N
O
N
O
Cu(DS)2
DS = dodecyl sulfate (3OSOC12H25)
Lewis Acid-Surfactant Combined Catalyst Systems
Kobayashi, S. et. al. Green Chem. 1999, 4, 175-177
20 mol %
(10 mol %)
13
OSi(CH3)3 H
O
Yb(OTf)3 (10 mol%) / H2O-THF(1:4)
R.T., 19 hr, 91% yield
OH O
Lanthanide Triflate as Water-Tolerant Lewis Acid
Kobayashi, S. et. al. J. Org. Chem. 1994, 13, 3590-3596
14
Polystyrene Supported Formamide Catalyzed Mukaiyama Aldol Reaction
H
O
SiCl3
OH
N H
O
PS-Formamide 1
100 mol%
CH3CN , rt, 9 hr
91%
3 eq.
Ogawa, C.; Sugiura, M.; Kobayashi, S. Chem. Commun. 2003, 192-193
15
Cl
H
O
OMe
OTMSN N ( )n
Cl-
n=7
Cl
OMe
OOH
74% yield, 12hr
Ionic Liquid Catalyzed Mukaiyama Aldol Reaction
Loh, T. P. et. al. Tetrahedron Lett. 2004, 45, 375-377
16
Motivation
I. Traditional Lewis acids are difficult to handle
II. Lanthanide metals are relatively expensive
III. Low Oxidation State Transition Metals
a. Relatively high moisture – and oxygen – stability
b. Inexpensive
c. Tunable electronic and steric environments around metal Lewis
acid center
IV. Green Chemistry
a. Green solvents
R.T. ionic liquids (BmimPF6) and H2O
b. Energy saving
Catalysis under microwave irradiation
17
Preparation of Organomolybdenum Catalyst Thermal Conditions
NN
N
N NN
Mo
OCCOOC
P
O
reflux (82oC) / 18 hrdry CH3CN
MoCO
COCO
CO
OC
OCPO
N NN
Mo
OCCOOC
PO
2 eq NOBF4
0oC / stir 1 hrN
NN
Mo
ONNOOC
PO
2+
(BF4-)2
dry CH3NO2
80% yield
75% yield
18
Microwave Flash Heating Conditions
NN
N
NN
N
Mo
OC
COOC
P
O
uw(300W/100%)/ 120 oC/ 5 min
dry CH3CN
MoCO
COCO
CO
OC
OC
PO
NN
N
Mo
OC
COOC
PO
2 eq NOBF4
0oC / stir 1 hrN
NN
Mo
ON
NOOC
PO
2+
(BF4-)2
dry CH3NO2
90 % yield
75 % yield
19
H3
O
H2
O
H3
L.A.O
L.A.
H1
H2
CH34
L.A.
H3
CH34
H1 H1
H2
CH34
H2
O
H3
CH34
H1
L.A.
Crotonaldehyde-Lewis Acid Adduct
Childs, R. F. et. al. Can. J. Chem. 1982, 60, 801
CH34
H3
H2
H1O
L.A.
H3
CH34
H2
H1 OL.A.
20
chemical shift diff.
Lewis acid
△δ on H3
(ppm)
BBr3 1.49
AlCl3 1.23
[OP(2-Py)3W(CO)(NO)2](SbF6)2 1.23
[OP(2-Py)3W(CO)(NO)2](BF4)2 1.22
[OP(2-Py)3W(CO)(NO)2](SbF6)2 1.21
[HOC(2-Py)3W(CO)(NO)2](SbF6)2 1.19
[P(2-Py)3W(CO)(NO)2](BF4)2 1.18
BF3 1.17
AlEtCl2 1.15
[HC(2-Py)3Mo(CO)(NO)2](SbF6)2 1.05
TiCl4 1.03
[P(2-Py)3Mo(CO)(NO)2](BF4)2 1.01
[OP(2-Py)3Mo(CO)(NO)2](BF4)2 0.992
[Me3P(CO)3(NO)W]+ 0.93
SnCl4 0.87
[CpMo(CO)2]+(PF6) 0.70
Et3Al 0.63
[CpFe(CO)2]+BF4 0.54
21
Organomolybdenum Lewis Acid Catalyzed Mukaiyama Aldol Reactions under Thermal
Conditions
F
Cl3C H
O
R =O2N
4-notrobenzaldehyde
Trichloro-acetaldehyde
4-fluorobenzaldehyde
Benzaldehyde
Si(CH3)3
Sn(C4H9)3
Sn(C6H5)3
R' =
allyltrimethylsilane
allyltributyltin
allyltriphenyltin
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN or DMF or CH3NO2, R.T. or 40 oC or 70 oC
22
Entry R R' Yield (%)
CH3CN DMF
1 65 72
2 >99 83
3 61 77
4 79 77
5 59 76
6 59 64
O2N
O2N
O2N
F
F
F
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN or DMF , RT, 5 hr
23
Entry R R' Yield (%) CH3CN DMF
7 89 97
8 96 94
9 98 96
10 45 <10
11 36 79
12 75 71
CCl3
CCl3
CCl3Sn(C6H5)3
Sn(C6H5)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN or DMF , RT, 5 hr
24
Entry R R' Yield (%)CH3CN DMF
Entry R R' Yield (%)CH3CN DMF
1 89 97 7 79 77
2 96 94 8 59 76
3 98 96 9 59 64
4 65 72 10 45 17
5 99 83 11 36 90
6 61 77 12 75 71
[O=P(2-py)3Mo(CO)(NO)2](BF4)2
R H
OR'
R
OH
CH3CN or DMF , R.T. / 5 hr
CCl3
O2N
F
Si(CH3)3
Sn(C4H9)3
Sn(C6H5)3
CCl3
CCl3
O2N
O2N
F
F
Si(CH3)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
Sn(C6H5)3
CCl3 O2N F> ≈ >DMF : 3.82 ; 36.7
CH3CN : 3.92 ; 37.5
25
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN, DMF, CH3NO2 , 40oC, 5 hr
Entry R R' Yield (%)
1 43 72 28
2 >99 85 62
3 77 84 39
4 87 95 90
5 80 84 68
6 89 86 27
O2N
O2N
O2N
F
F
F
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
CH3CN DMF CH3NO2
26
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN, DMF, CH3NO2 , 40oC, 5 hr
Entry R R' Yield (%)
7 93 93 87
8 92 95 71
9 >99 95 65
10 36 68 53
11 56 65 50
12 60 76 47
CH3CN DMF CH3NO2
CCl3
CCl3
CCl3 Sn(C6H5)3
Sn(C6H5)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
27
Entry R R' Yield (%) Entry R R' Yield (%)
1 93 93 87 7 43 72 28
2 92 95 70 8 99 85 62
3 99 95 65 9 77 84 39
4 87 95 90 10 36 68 53
5 80 84 68 11 56 65 50
6 89 86 27 12 60 76 47
CCl3
O2N
F
Si(CH3)3
Sn(C4H9)3
Sn(C6H5)3
[O=P(2-py)3Mo(CO)(NO)2](BF4)2
R H
OR'
R
OH
CH3CN or DMF or CH3NO2 ,40 oC / 5 hr
CCl3
CCl3
O2N
O2N
F
F
Si(CH3)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
Sn(C6H5)3
CCl3O2NF
> >
DMF : 3.82 ; 36.7
CH3CN : 3.92 ; 37.5
CH3NO2 : 3.46 ; 35.87
≈
CH3CN DMF CH3NO2 CH3CN DMF CH3NO2
28
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN, DMF, 70oC, 5 hr
Entry R R' Yield (%)
1 61 88
2 >99 89
3 65 92
4 81 78
5 46 82
6 75 79
O2N
O2N
O2N
F
F
F
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
CH3CN DMF
29
Entry R R' Yield (%)
7 81 91
8 >99 93
9 92 85
10 33 62
11 <10 70
12 <10 75
CCl3
CCl3
CCl3 Sn(C6H5)3
Sn(C6H5)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN, DMF, 70oC, 5 hr
CH3CN DMF
30
Thermal Heating
Convection transition
Liquid boiling temperature is always lower than surface temperature of container
31
Interactive Characteristic between Materials and Microwave
Conductor (Metal Material)
Reflective
Insulator (Telflon)
Transparent
Dielectric Materials (Water)
Absorptive
32
Mechanism of Microwave Heating
Dipole Rotation
33
Ionic Conduction
34
Microwave Flash Heating
Microwave energy
Liquid raises temperature quickly
Digestion bottle
35
Organomolybdenum Lewis Acid Catalyzed Mukaiyama Aldol Reactions under Microwave
Irradiation Conditions [O=P(2-py)3Mo(CO)(NO)2](BF4)2
10 moi%
R H
OR'
R
OH
CH3CN or DMF or R.T.BmimPF6
mw (60W) , 40oC
F
Cl3C H
O
R =O2N
4-notrobenzaldehyde
Trichloro-acetaldehyde
4-fluorobenzaldehyde
Benzaldehyde
Si(CH3)3
Sn(C4H9)3
Sn(C6H5)3
R' =
allyltrimethylsilane
allyltributyltin
allyltriphenyltin
36Seddon, K. R. et. al. Pure Appl. Chem. 2000, 72, 2275–2287
Ionic Liquids
37
Entry R R' Time Yield (%)
(min) CH3CN DMF BmimPF6
1 10 64 81 86
2 10 >99 67 85
3 10 81 76 55
4 10 <10 66 70
5 10 69 69 84
6 10 70 77 <10
O2N
O2N
O2N
F
F
F
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN, DMF, BmimPF6, 40 oC mw (60W)
38
Entry R R' Time Yield (%)
(min) CH3CN DMF BmimPF6
7 10 24 88 85
8 10 72 85 78
9 10 34 95 <10
10 10 66 71 65
11 10 73 80 84
12 10 70 72 <10
[O=P(2-py)3Mo(CO)(NO)2](BF4)210 mol%
R H
OR'
R
OH
CH3CN, DMF, BmimPF6, 40 oC mw (60W)
CCl3
CCl3
CCl3 Sn(C6H5)3
Sn(C6H5)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
39
Entry R R' Yield(%)
Thermal mw
(5hr) (10mim)
Entry R R' Yield (%)
Thermal mw
(5hr) (10mim)
1 93 64 7 43 24
2 92 >99 8 99 72
3 99 81
9 77 34
4 87 <10 10 36 66
5 80 69 11 56 73
6 89 70 12 60 70
[O=P(2-py)3Mo(CO)(NO)2](BF4)2
R H
OR'
R
OH
CH3CN, 40 oC
CCl3
O2N
F
Si(CH3)3
Sn(C4H9)3
Sn(C6H5)3
CCl3
CCl3
O2N
O2N
F
F
Si(CH3)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
Sn(C6H5)3
40
Entry R R' Yield (%)
Thermal mw
(5hr) (10mim)
Entry R R' Yield (%)
Thermal mw
(5hr) (10mim)
1 93 81 7 72 88
2 95 67 8 85 85
3 95 76 9 84 95
4 95 66 10 68 71
5 84 69 11 65 80
6 86 77 12 76 72
[O=P(2-py)3Mo(CO)(NO)2](BF4)2
R H
OR'
R
OH
DMF, 40 oC
CCl3
O2N
F
Si(CH3)3
Sn(C4H9)3
Sn(C6H5)3
CCl3
CCl3
O2N
O2N
F
F
Si(CH3)3
Si(CH3)3
Si(CH3)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C4H9)3
Sn(C6H5)3
Sn(C6H5)3
Sn(C6H5)3
41
Solvent Dipole moment Dielectric constant
CH3NO2 3.46 35.87
CH3CN 3.92 37.5
DMF 3.82 36.7
BmimPF6 1.66~1.68 …
Dipolemoment and Dielectric Constant of Catalytic Solvent Systems
Reactivity under Thermal Conditions: DMF > CH3CN > CH3NO2
Reactivity under Microwave : BmimPF6 > DMF > CH3CN
42
Proposed Mechanism
N NN
P
MoNOOC
O
NO
2+
( BF4- )2
- CON NN
P
MoNO
O
NO
2+
( BF4- )2
H
O
R
N NN
P
MoNO
O
NO
2+
( BF4- )2
H
O
R
R'
nucliphilic attack
N NNMo
NO
NO
2+
( BF4- )2
H
O
R
R'
P
O
σ-donation
43
N NN
MoNO
NO
2+
( BF4- )2
O
R
HR'
N NN
P
MoNO
O
ON
2+
( BF4- )2
O
R
H
R'
P
O
OR'
R
HN N
N
P
MoNO
O
NO
2+
( BF4- )2
H2O
hydrolysis
OH
R
H R'OH
44
Catalysts
A(2-py)3 M
Yield (%)
O=P(2-py)3 Mo 93
P(2-py)3 Mo 85
O=P(2-py)3 W 56
P(2-py)3 W 45
Catalytic Reactivity of [A(2-py)3M(CO)(NO)2]2+ on Mukaiyama Aldol Reaction
Cl3C
O
Si(CH3)3
DMF, 40oC, 5h
10 mol%Cl3C
OHCatalyst
45
Catalytic Reactivity of [A(2-py)3M(CO)(NO)2]2+
on Diels Alder Reaction
bmimPF6
3 mol% cat. O
O
Catalysts
A(2-py)3 M
Concentration (M)/Time (min)
Yield (%)
endo: exo
O=P(2-py)3a
W 0.67 / 45
97
(90:10)
O=P(2-py)3 Mo 0.67 / 45
85
(90:10)
P(2-py)3b
W 0.022 / 30
87
(94:6)
HO-C(2-py)3c W 2.256*10-3 / 24
66
(91:9)
a: 陳宜宏碩士論文 “水溶性有機鎢金屬路易士酸在綠色溶劑及微波中對於 Diels-Alde 反應的影響”
中正大學化學研究所 , 2003
c: 施子芳碩士論文 “有機鎢金屬路易士酸的合成及其催化反應活性之探 中正大學化學研究所 , 1998
b: 傅耀賢博士論文 “過渡金屬錯合物觸媒的合成、催化活性以及動力學研究 中正大學化學研究所 , 2001
46
Conclusions
1. 本實驗成功地合成出有機金屬鉬路易士酸 [O=P(2-py)3Mo(CO)(NO)2](BF4)2 , 並將催化劑應用於 Mukaiyama 醛醇反應,分別在傳統加熱與微波照射系統反 應條件下,對一系列的 Mukaiyama 醛醇反應具有很好的催化效果。
2. 利用微波系統取代傳統加熱法可有效地縮短反應時間與提升能源效率。
3. Mukaiyama 醛醇反應在不同溶劑系統下,皆有很好的催化效果,且當溶劑系統為低極性與低介電常數時,催化效果比較好。
4. 本實驗利用綠色溶劑室溫離子液體 (BmimPF6) 取代有機溶劑的使用,可有效地進行 Mukaiyama 醛醇反應,同時也符合綠色化學的宗旨。
5. Mukaiyama 醛醇反應與 Diels-Alder 加成反應對 [A(2-py)3M(CO)(NO)2]2+ 催化劑之催化效率,與 A 和 M (A = HO-C 、 P 、 O=P 和 M = Mo 、 W) 有關。對 Mukaiyama 醛醇反應而言,當 M = Mo 時,具較好的催化效果 ; 當 A= P(O) 時,具較好的催化 效果。對 Diels-Alder 加成反應而言,當 M = W時,具較好的催化效果 ; 當 A = P 時,具較好的催化效果。
6. 本實驗合成出具水溶性的催化劑有機金屬鉬路易士酸,且在水中的溶解度可達 23 g/L ,因此,可進一步將有機金屬鉬路易士酸應用於水相的催化系統。