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


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


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


R H

OR'

R

OH

CH3CN, DMF, CH3NO2 , 40oC, 5 hr


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


R H

OR'

R

OH

CH3CN, DMF, CH3NO2 , 40oC, 5 hr


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


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


R H

OR'

R

OH

CH3CN, DMF, 70oC, 5 hr


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


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


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


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


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)


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


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


Thermal mw

(5hr) (10mim)


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


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。

1 microwave assisted organomolybdenum lewis acid catalyzed mukaiyama aldol reactions student :...

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