1

Synthesis, Characterization and Catalytic Application of Aminodipyridylphosphine Oxide Palladium(II) Complex and Its Supported Form

on Gold Nanoparticles

日期： 2013.7.15學生：陳盈源

指導教授：于淑君 博士

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Characteristics of catalysts Homogenous Heterogeneous Hybrid

Cat. structure Known Unknown Known

Quantitative analysis Easy Difficult Easy

Catalyst modification Easy Difficult Easy

Activity High Low High

Conditions of catalysis Mild Harsh Mild

Poisoning of cat. High risk Low risk Low risk

Mechanical strength Low High High

Cat. stabilities Low High High

Separation ＆ recycle of cat. Difficult Easy Easy

Industrialization Difficult Applicable Applicable

Types of Catalysts

3

A

MM

A

= Molecular Metal Complex Catalyst

= Spacing Linker

= Anchoring Group

= Metal or Metal Oxide or Polymer Surface

Concept ：

1. Increasing the Heterogeniety of the Homogeneous Catalyst Systems.

2. Combining Both Benefits of Homogeneous and Heterogeneous Systems.

Supported Catalysts

4

Gold nanoparticles (AuNPs) have been

known not only to possess solid surfaces

resembling the (1 1 1) surface of bulk gold

but also to behave like soluble molecules for

their dissolvability, precipitability, and

redissolvability.

Hybrid Catalyst Design

= Functional Groups

= Bidentate chelate Ligands

= Spacing Linker

Soluble Metal Complex

AuNPswith Controllable Solubility

MAuNPs

5

Spacing Linker

HS NH

PO N

NMAuNPs

Phosphine ligand Phosphines are electronically and sterically tunable.

Air sensitive metal leaching

P-C, P-OR cleavage under high temperature.

Hazard waste

High cost

P

P(Bu)3

P

OOO

P(OiPr)3

P

P(Me)3

P

P(o-tolyl)3

Bidentate chelate effect

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The Catalytic Applications of Palladium(II)

Advantages ： Functional group tolerance

Exhibit higher TOF

Suitably stable against water or air.

Heck

Stille

Suzuki

Sonogashira

Buchwald-Hartwig

Tsuji-Trost

Negishi

Oxidation of Alkenes

Oxidation of Alcohols

Allylation of Aldehydes

Strecker Reaction

N-vinylation of amides

Diverse Catalytic Reactivity ：

+ OAcPd cat.

SHN

O

O

S

O

O

NR

R

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Enamides

NEWGR

EWG = electron withdrawing group = C(O)R - Enamide = C(O)OR - Enecarbamate = SO2R - Ensulfonamide

NH

NHO

NH

chondriamide Canthelmintic activity

MeO

Br

Br

HNO

MeO

OH

botryllamide Acytotoxicity against colon cancer cells

OH

O

O

HN

O

Me

OH

salicylihalamide Acytotoxicity against human cancer cells

OH

O

OO

HN

O

OHapicularen Aantitumor activity

OH O

O

HN

ON

OMe

oximidine IIantitumor antibiotic

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NEWG

REnamides

RadicalReactions

Photochemical Reactions

PericyclicReactions

Transition MetalCatalysed Reactions

HetreocyclicSynthesis

The Chemistry of Enamide

NuceophilicReactions

ElectrophilicReactions

Application of Enamides

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1. To study the immobilization of molecular Pd(II) complexes on the surfaces of AuNPs by using the covalent linkage via a specially designed bipyridine ligand as spacing linkers.

2. Palladium catalyses have several advantages including functional group tolerance, exhibit higher TOF, and are suitably stable to run the reactions without the exclusion of water or air.

3. Using bipyridine ligand to replace phosphine ligand in organomatallic catalysis.

4. AuNPs have been known not only to possess solid surfaces resembling the (1 1 1) surface of bulk gold but also to behave like soluble molecules for their dissolvability, precipitability, and redissolvability.

Motivation

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5. To design an easily recovered and effectively recycled AuNPs supported palladium(II) complex catalyst.

6. Because AuNPs are microwave conductor like bulk gold, we will apply microwave flash heating to replace conventional thermal heating.

Motivation

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1.NaN3 / DMF

2. rt / 6 h

1. P(2-py)3 / CH3CN

2. DI water

3. reflux / 90oC / 16 hr

Pd(OAc)2 / CHCl3

rt / N2 / 3 hrNH

PO N

NPd

OAc

OAcNH

PO N

NHO5

HO5

NH

PO N

NHO5HO

5N3HO

5Br

96 % 75 %

HO-C11-Ppy2-Pd50 %

Synthesis of HO-C11-Ppy2-Pd

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1H NMR Spectrum of HO-C11-Ppy2-Pd

HO NH

PO N

N HO NH

PO N

NPd

OAc

OAc

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IR Spectrum of HO-C11-Ppy2-Pd

HO-C11-Ppy2

HO-C11-Ppy2-Pd

Pd(OAc)2

1614 cm-1`

Nagaki, A.; Takabayashi, N.; Moriwaki, Y.; Yoshida, J.-i. Chemistry – A European Journal 2012, 18, 11871.

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NaN3 / DMF/ H2O

50 oC / 6 hrBr N3

1.P(2-py)3 / CH3CN

2. DI water

3. 80 oC / 16 hr

NH

PO N

N

87 %55 %

NH

PO N

N

Pd(OAc)2 / CHCl3

rt / N2 / 5 hrNH

PO N

NPd

OAc

OAc

C4-Ppy2-Pd64 %

Synthesis of C4-Ppy2-Pd

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1H NMR Spectrum of C4-Ppy2-Pd

NH

PO N

N NH

PO N

NPd

OAc

OAc

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IR Spectrum of C4-Ppy2-Pd

C4-Ppy2

C4-Ppy2-Pd

Pd(OAc)2

1614 cm-1`Nagaki, A.; Takabayashi, N.; Moriwaki, Y.; Yoshida, J.-i. Chemistry – A European Journal 2012, 18, 11871.

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Crystal Structure of C4-Ppy2-Pd

Bond legths [Å] and Bond angles []

Pd(1)-N(1) 2.016

Pd(1)-N(2) 2.024

Pd(1)-O(2) 2.010

Pd(1)-O(4) 2.001

Pd(1)-O(3) 3.030

Pd(1)-O(5) 2.926

N(1)-Pd(1)-N(2) 92.06

O(2)-Pd(1)-O(4) 90.31

N(1)-Pd(1)-O(4) 174.50

N(2)-Pd(1)-O(2) 178.73

NH

PO N

NPd

OAc

OAc

Hydrogen bond

d(N3H3) d(H3O3) d(N3O3)

0.86 Å 2.24 Å 3.077 Å

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0.0461 Å

Crystal Structure of C4-Ppy2-Pd

N2 N1

O4 O2

Pd

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HS NH

PO N

N

S

S

SSSS

SSNH

PO N

NPd

OAc

OAcRS-AuL

65 oC / 16 hr / CHCl3

RS-Au-SLPd(OAc)2

45 oC / 3 hr

L =

SR = HS

Au

RS-Au-L-Pd

Synthesis of RS-Au-L-Pd

20Hostetler, M. J.; Templeton, A. C.; Murray, R. W. Langmuir 1999, 15, 3782.

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1H NMR Spectrum of RS-Au-L-Pd

NH

PO N

NHS5

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IR Spectrum of RS-Au-L-Pd

RS-Au-L

RS-Au-L-Pd

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EDS and TEM Image of RS-Au-L-Pd

1.675 0.3164 nm

Element Weight Atomic

C 5.1 26.93

Cu 59.41 59.28

Pd 8.65 5.16

Au 26.84 8.64

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Reaction Conditions Screening

Entry CatalystK2CO3

(eq)Temp (oC)

Time (hr)

Conv. ()

1 C4-Ppy2-Pd 1 rt. 7.3 0

2 RS-Au-L-Pd 1 rt. 7.3 0

3 RS-Au-L-Pd 1 120 6 12

4b RS-Au-L-Pd 1 95 22 38

5 RS-Au-L-Pd 1 65 6 52Reaction conditions ： a. sulfonamide (0.25 mmole), vinyl acetate (500 L) , CHCl3 (100 L).

b. catalyst (7 mol ).

+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3

SHN

O

O

I S

O

O

N

I

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Reaction Conditions Screening

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Reaction Conditions Screening

Entry CatalystK2CO3

(eq)Temp (oC)

Time (hr)

Conv. ()

5 RS-Au-L-Pd 1 65 6 52

6 RS-Au-L-Pd 2 65 6 83

7 RS-Au-L-Pd 3 65 6 93

8 RS-Au-L-Pd 4 65 6 94

9c RS-Au-L-Pd 3 65 6 99Reaction conditions ：a. sulfonamide (0.25 mmole), vinyl acetate (500 L), CHCl3 (100 L).

c. sulfonamide (0.25 mmole), vinyl acetate (600 L), CHCl3 (120 L).

+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3

SHN

O

O

I S

O

O

N

I

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Reaction Conditions Screening

Entry CatalystK2CO3

(eq)Temp (oC)

Time (hr)

Conv. ()

10c C4-Ppy2-Pd 3 65 6 96

11c C4-Ppy2-Pd 3 65 4 97

12c C4-Ppy2-Pd 3 65 3 94

13c C4-Ppy2-Pd 3 65 2 93

14c C4-Ppy2-Pd 3 65 1 85

Reaction conditions ：c. sulfonamide (0.25 mmole), vinyl acetate (600 L), CHCl3 (120 L).

+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3

SHN

O

O

I S

O

O

N

I

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Reaction Conditions Screening

Entry Solvent Polarity (P) Conv. ()

1 DMSO 7.2 78

2 Acetonitrile 5.8 97

3 CHCl3 4.1 95

4 Toluene 2.4 96

5 Hexane 0 95

6 [Bmim]PF6 87

Reaction conditions ： sulfonamide (0.25 mmole), vinyl acetate (600

L), catalyst (2 mol ), K2CO3 (3 eq), solvent (120 L), 65 oC, 2 hr.

SHN

O

O+ OAc

HO-C11-Ppy2-Pd 2 mol %

K2CO3 / solvent / 65 oC / 2 hr

S

O

O

N

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Catalytic N-Vinylation of amides by Pd Catalyst

Entry RConv. ()

C4-Ppy2-Pd HO-C11-Ppy2-Pd RS-Au-L-Pd

1 4-OMe 98 98 87

2 4-Me 95 99 90

3 H 94 96 87

4 4-I 94 97 91

5 4-F 96 99 99

6 4-CF3 90 90 87

7 3,5-dimethyl 97 98 96

8 2,6-dimethyl 57 58 49

9 2-I 71 76 74

10 2-Me 93 95 93

Reaction conditions ： sulfonamide (0.25 mmole), vinyl acetate (600 L), catalyst (2 mol ), K2CO3 (3 eq), CHCl3 (120 L), 65 oC, 2 hr.

+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl365 oC / 2 hr

SHN

O

O

S

O

O

NR

R

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Entry Rvinyl acetate

(L)CHCl3 (L)

Total volume (L)

Conv. ()

1 4-OMe 600 1080 1680 90

2 4-Me 600 1080 1680 89

3 H 600 1080 1680 91

4 4-I 600 1080 1680 90

5 4-F 600 1080 1680 93

6 4-CF3 600 1080 1680 86

+ OAc

HO-C11-Ppy2-Pd 2 mol %

K2CO3 / CHCl365 oC / 2 hr

SHN

O

O

S

O

O

NR

R

Electronic Effect ?

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Recyclability of Catalyst

SHN

O

O+ OAc

RS-Au-L-Pd ( 20 mol %)

K2CO3 / 45 oC / 20 min

S

O

O

N

RS-Au-L-Pd < 0.16 metal leaching

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Catalyst Recycling Efficiency

CatalystSolvent consumed

(mL)Cat.

recovery

Mechanical loss +

Metal leachingConv. ()

RS-Au-L-Pd EA (2 mL 2) = 4 > 97 < 3 97 86 (9 cycles)

C4-Ppy2-Pd

CHCl3 (2 mL 6)

+

Ether (4 mL 5)

= 32 ~ 33 ~ 67 98 33

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+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3microwave

SHN

O

O

S

O

O

N

Entry MW[Bmim]PF6

(L)

Time

(min)

Conv.

()

1 75 20 5 50

2 85 20 5 47

3 95 20 5 45

4 95 20 7 48

5 150 20 5 49

6 200 20 5 -Reaction conditions ： sulfonamide (0.25 mmole), vinyl acetate (600 L), HO-C11-Ppy2-Pd (2 mol ), CHCl3 (120 L), K2C03 (3 eq), microwave.

Reaction Conditions Screening under Microwave

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+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3microwave

SHN

O

O

S

O

O

N

Entry MW[Bmim]PF6

(L)

Time

(min)

Conv.

()

7 150 10 5 55

8 150 5 5 60

9 200 5 5 57

10 250 5 5 65

11 300 5 5 65

12 300 5 10 72

13 300 5 15 72Reaction conditions ： sulfonamide (0.25 mmole), vinyl acetate (600 L), HO-C11-Ppy2-Pd (2 mol ), CHCl3 (120 L), K2C03 (3 eq), microwave.

Reaction Conditions Screening under Microwave

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+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3microwave

SHN

O

O

S

O

O

N

Entry MWTime

(min)

Conv.

()

14 150 5 41

15 150 10 75

16 150 15 86

17 150 20 96

18 200 10 85

19 200 15 93

20 200 20 96

21 250 10 82Reaction conditions ： sulfonamide (0.25 mmole), vinyl acetate (600 L), HO-C11-Ppy2-Pd (2 mol ), CHCl3 (120 L), K2C03 (3 eq), microwave.

Reaction Conditions Screening under Microwave

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Entry RConv. ()

C4-Ppy2-Pd HO-C11-Ppy2-Pd RS-Au-L-Pd

1 4-OMe 96 94 85

2 4-Me 94 96 84

3 H 92 91 88

4 4-I 96 95 84

5 4-F 99 99 97

6 4-CF3 88 90 80

7 3,5-dimethyl 97 97 92

8 2,6-dimethyl 47 53 46

9 2-I 70 76 66

10 2-Me 91 95 83

+ OAcPd cat. 2 mol %

Microwave : 200 W, 20 minS

HN

O

O

S

O

O

NR

R

Microwave Assisted Pd-Catalyzed N-Vinylation of amides

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Entry R

Conv. ()

C4-Ppy2-Pd HO-C11-Ppy2-Pd RS-Au-L-Pd

Thermal MW Thermal MW Thermal MW

1 4-OMe 98 96 98 94 87 85

2 4-Me 95 94 99 96 90 84

3 H 94 92 96 91 87 88

4 4-I 94 96 97 95 91 84

5 4-F 96 99 99 99 99 97

6 4-CF3 90 88 90 90 87 80

7 3,5-dimethyl 97 97 98 97 86 92

8 2,6-dimethyl 57 47 58 53 49 46

9 2-I 71 70 76 76 74 66

10 2-Me 93 91 95 95 93 83

+ OAc

Pd cat. 2 mol %

Thermal : 65 oC, 2 hr

Microwave : 200 W, 20 min

SHN

O

O

S

O

O

NR

R

Microwave Assisted Pd-Catalyzed N-Vinylation of amides

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Mechanism of Enamide Formation

PdOAc

OAc

L

L

PdOAc

N

L

L Ar

Ts

PdN

OAcLL

AcOAr

Ts

intermediate Bintermediate A

TsNHAr + K2CO3

1

KHCO3 + KOAc

OAc

2

NAr Ts

3

Xu, J.; Fu, Y.; Xiao, B.; Gong, T.; Guo, Q., Tetrahedron Letters 2010, 51 (41), 5476-5479.

39

Conclusions

1. We have developed a mild and efficient protocol for the Pd-catalyzed N-vinylation of amides with vinyl acetate.

2. The AuNPs supported Pd(II) complex catalyst not only provide comparable reactivity with its unbound form, but also offer excellent catalyst recyclability.

3. Further acceleration of the Pd(II) catalyzed N-vinylation was achieved under microwave irradiation conditions.

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NR N N + Pyppy

pyNR

N NP

yp

py

py N P

N N

pyR py

py

NR P pypy

py

H2ONR P py

py

py

HO+ H R N P

OH

pypy

+ py + H

R N P

O

pypy

H

R N P

O

pypy

H

N2+

非傳統 Staudinger 反應

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Entryvinyl acetate

(L)CHCl3 (L)

AdditiveTime(hr)

Conv. ()

1 600 120 - 1 96

2 600 120 AuNPs 1 96

3 600 1080 - 1 79

4 600 1080 AuNPs 1 76

+ OAc

C4-Ppy2-Pd 2 mol %

K2CO3 3 eq

65 oC / 1 hr

SHN

O

O

S

O

O

N

AuNPs of Influence

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Entry MWTime

(min)

Conv. ()

HO-C11-Ppy2-Pd C4-Ppy2-Pd RS-Au-SL-Pd

1 150 10 78 60 65

2 150 15 86 84 80

3 150 20 96 91 82

4 200 10 85 75 67

5 200 15 93 89 81

6 200 20 96 94 84

Reaction conditions ： 1 (0.25 mmole), 2 (600 L), K2CO3 (3eq), CHCl3 (120 L), catalyst (2 mol ), microwave ： 200 W, 20 min.

+ OAc

Pd cat. 2 mol %

K2CO3 / CHCl3microwave

SHN

O

O

S

O

O

N

1 2

Reaction Conditions Screening under Microwave

43

HO-C11-Ppy2-Pd

HO-C11-Ppy2-Pd 65oC 2 hr