Department of Chemistry & Biochemistry Chung Cheng University

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The Study of Catalytic Application of N-Heterocyclic Carbene Copper(I) Complex in Both Molecular and Supported Forms on

Huisgen Cycloaddition Reactions.

學生：莊雲婷指導教授：于淑君　博士

2010 / 05 / 03Department of Chemistry & Biochemistry

Chung Cheng University

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Phosphine Ligand

Phosphines are electronically and sterically tunable.

Expensive.

Air sensitive.

Metal leaching.

Chemical waste.

P P PPOO

O

P(Bu)3 P(OiPr)3 P(Me)3 P(o-tolyl)3

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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 andoffer catalysts with better air-stability.

[M]

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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

WCO

COOCCOOC V

NHCCHNNHCCHN

Cl

ClTi ClCl

ClClNN

N N

Me Me

MeMe

Re OOO

Me

N NMe Me RuPCy3

Ph

NNMesMes

ClCl

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The Catalytic Applications of CuI

O-arylation of Phenols

Kharasch-Sosnovsky Reaction (Allylic Oxidations of Olefins)

S-arylation of Thiols

N-arylation of Amines (Buchwald-Hartwig Reaction)

Hydrosilylation of Ketones

Heck reaction

Oxidation of Alcohols

Substitution Reaction

Epoxidation Reaction

Reductive Aldol Reaction

1,3-dipolar cycloaddition

Carl Glaser. Berichte der deutschen chemischen Gesellschaft 1869. 2, 422–424.

Sonogashira Reaction

CuCl, O2

NH4OH, EtOH

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Drawbacks of Traditional Copper-Mediated Reactions

insoluble in organic solvents - heterogeneous

harsh reaction conditions - high temperatures around 200 °C - strong bases - toxic solvent such as HMPA - sensitive to functional groups on aryl halides - long reaction times - the yields are often irreproducible

structure not clear

Girard, C. Org. Lett., 2006. 1689-1692

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Catalyst supported onto Au NPs surface

soluble metal complex

functional groups

coordinationl ligands

spacer linker

catalyst

Au NPs 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.

Lin, Y.-Y; Tsai, S.-C.; Yu, S. J. J. Org. Chem. 2008, 73, 4920-4928.

Au NPs with controllable solubility

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Motivation

Using NHCs ligand to replace phosphine ligand inorganomatallic catalysis.

Base on economic standpoint, copper metal is cheaperthan palladium catalyst . - PdCl2 $4805.00(150g) ReagentPlus® (Aldrich) - CuCl $206.00(100g) ReagentPlus® (Aldrich)

Synthesis of NHC-Cu(I) complexes with well-defined structures.

Greener catalysis – microwave and solventless conditions.

Easily recovered and effectively recycled catalyst NHC-Cu(I) complexs by immobilization onto Au NPs.

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The First Isolable Carbene-CuI Complexes

Arduengo, A. J., III; Dias, H. V. R.; Calabrese, J. C.; Davidson, F. Organometallics 1993, 12, 3405-3409.

N

NH

t-BuOK

THF

N

N

N

N N

NCu+

CF3SO3-

M = Cu

Cu+-O3SCF3

THF

Cl

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hmim = 1-hexyl-3-methylimidazolium

Preparation of CuI Complex Catalyst

Br

NN

65 oC, 12 hyield = 95 %

NNBr

CuI, t-BuONa

THF reflux, 24hyield = 96 %

(hmim)HBr(1)

NN

CuI(hmim)(2)

CuI

Preparation of (HS-hmim)HPF6

Br Br

NN

DMF, 65 oC, 16 hyield = 95 %

NN BrBr

1. CS(NH2)2, EtOH reflux, 16 h2. NaOH, 20oC, 3 min3. HCl, 20oC, 20 min

Yield = 70 %

NN SHBr

KPF6, H2O

0oC, 30 minyield = 53 %

NN SHPF6

(HS-hmim)HPF6(3)

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NN (CH2)6 S

Cl

2

+ HAuCl4NaBH4

NN (CH2)6 SH

Cl

Aun

Photographs of the obtained solutions of the 1-modified gold NPs after addition of (a) HCl (b) HBr (c) HBF4 (d) HI (e) HPF6.

Chujo.Y. J. Am. Chem. Soc. 2004, 126, 3026-3027

Synthesis of Gold Nanoparticles Modified with Ionic Liquid

(a) (e)

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TOAB = tetra-octyl ammonium bromideSR = Octane thiol

Au(SR) size : 2.4 0.39 nm

Synthesis of Octanethiol Protected Au NPs

HAuCl4 -4H2O

[CH3(CH2)7]4N+Br-

CHCl3, 1 h CHCl3. 15 min

NaBH4

H2O, 8 min S

SSAu

Au(SR) (4)

SH

SRTOAB

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IL = (S-hmim)(HPF6)

Au(SR)(IL) size : 2.04 0.7 nm

Synthesis of Au NPs Modified with Ionic Liquid

S NS

Au NPF6

S

N N

PF6Au(SR)m(IL)n

(5)

S

SSAu

Au(SR) (4)

NN SHPF6

(3)

THF, 40 oC, 4 h

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HS-CH2-

HS-CH2-

-CH3

-CH3

-CH3

DMSO

(4)

SCH2

CH3

S

H2C CH3

Au

CH3

H2C

HS

SHCH2

N N

PF6

(3)

SCH2 N

S

H2C

Au

CH3

NPF6(5)

CHCl3

CHCl3

DMSO

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ILCu = S-hmim-CuCl

Au(SR)(IL)(ILCu) size : 1.63 0.32 nm

Synthesis of Au NPs Supported NHC-CuI complex

S NS

Au NPF6

S

N N

PF6Au(SR)m(IL)n

(5)

CuCl, t-BuONa

CH3CN, 60 oC, 24 hS N

SAu N

S

N

CuCl

Au(SR)x(IL)y(ILCu)z(6) N

CuCl

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-CH2-Hb

HbHa

-CH2-

-CH3

-CH3

*

*

#

#

H2O

H2O

DMSO

DMSO

NNH3CH2C

BrHa

Hb Hb(hmim)HBr

(1)

NNH3CH2C

CuI

Hb HbCuI(hmim)

(2)

1H NMR Spectra of (hmim)HBr (1) & (hmim)CuI (2)

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1H NMR Spectra of Au(SR)(IL) (5) & Au(SR)(IL)(ILCu) (6)

*d-DMSO

*d-DMSO#H2O

#H2O

HbHa

-CH2-

-CH3

Hb

-CH2-

-CH3

-CH3

-CH3

S H2C

N

SAu

CH3

N CH3

CuCl

HbHb

Au(SR)0.09(ILCu)1(6)

S H2C

N

SAu

CH3

N CH3

PF6

Ha

Hb Hb

Au(SR)0.17(IL)1(5)

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13C NMR Spectra of Au(SR)(IL) (5) & Au(SR)(IL)(ILCu) (6)

136.3 ppm

182.6 ppm

*DMSO

*DMSO

123.3 ppm121.9 ppm

123.6 ppm122.1 ppm

SN

SAu

C CN

C

PF6

H

Au(SR)0.17(IL)1(5) H H

S

N

SAu

C CN

CCuCl

Au(SR)0.09(ILCu)1(6) H

H

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IR Spectra of Ligand and NHC-CuI Series

CuI(hmim) (2)

(hmim)HBr (1)

Au(SR)(IL)(ILCu) (6)

Au(SR)(IL) (5)

4000 3500 3000 2500 2000 1500 10000

20

40

60

80

100

120

140

160

T (%

)

Wavenumber (cm-1)

(S-hmim)HPF6 (3)

1573

1636

1575

1677

1167

1229

1169

1218

2589

20

933

EDS and XPS of Au(SR)(IL)(ILCu) (6)

965 960 955 950 945 940 935 930

Inte

nsity

Binding Energy (eV)

932.8

2p3/2

2p1/2

Tubaro, C.; Tetrahedron. 2008. 4187-4195

Galtayries, A.; Bonnelle, J. -P. Surf. Interface Anal. 1995, 23, 171.

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R1NNN + R2N

NN

R1

R2

NN

NR1

R2

azide alkyne 1,4-disubstituted triazoles

1,5-disubstituted triazoles

+

The is a 1,3-dipolar cycloaddition between azide alkyne to give a 1,2,3-triazole

Rolf Huisgen was the first to understand this organic reaction at 1961.

K. Barry Sharpless and co-workers defined it as “a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries” Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004-2021

Azide-Alkyne Huisgen Cycloaddition

Anke Cwiklicki, A. Arch. Pharm. Pharm. Med. Chem. 2004, 337, 156−163

Huisgen, R. .Angew. Chem. Int. Ed. 1961. 11. 633–645.

22Fokin, V. V.; Jia, G.; Lin, Z. J. Am. Chem. Soc. 2008. 130. 8923–8930

2 mol % cat.Rt, 30 min

Yield = 63-97 %

Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057-3064

(i) 2 eq 2-Azido-2-methylpropionic acid, 50 eq DIPEA, 2 eq CuI.(ii) 0.1 M NaOH (aq).

Azide-Alkyne Huisgen Cycloaddition

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Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884

TOF(h-1)

33322255062

2022

180

66389

37.5394

Reported NHC-CuI Catalytic Huisgen Cycloaddition

[a] The conversion (determined by GC) is an average of the values for at least two independent experiments.

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Reported Mechanism for Azide-Alkyne Huisgen Cycloaddition


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(Hmim)CuI (2) Catalysis Huisgen Cycloaddition – Solvent Effect

Condition: Benzyl azide = 1 mmol, phenyl acetylene = 1.2 mmol. solvent = 0.25 mL, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR

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(Hmim)CuI (2) Catalysis Huisgen Cycloaddition


Condition: Benzyl azide = 1 mmol, phenyl acetylene = 1.2 mmol. solvent = 0.25 mL, RT, 0.05 mol% (hmim)CuI. The conversion is determined by 1H NMR

TOF(h-1)

333 2225 5062

27Condition: azide = 1 mmol, phenyl acetylene = 1.2 mmol. neat, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR


28


Condition: azide = 1 mmol, 1-nonyne = 1.2 mmol. neat, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR

29Condition: azide = 1 mmol, alkyne = 1.2 mmol. CH3CN = 0.25 mL, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR


30Wang, L. Tetrahedron. 2008. 64. 10825–10830

R2N

NN

R1

R2

N3 R1 +neat

1 mol %

N

NCuI

SiO2

Conditions: organic azide (1 mmol), alkyne (1 mmol), SiO2–NHC–Cu(I) (1 mol %). B Isolated yields.C At 80 oC for 24 h.

+

N3

NN

NR1

R2

1 mol %

RT , naet, 30 min

Cycle Yield(%)b Cycle Yield(%)b

1 93 6 92

2 93 7 90

3 91 8 90

4 92 9 88

5 89 10 87

N-Heterocyclic Carbenes CuI Supported on SiO2

TOF(h-1)=186

1.Structurally undefined

2.Quantitative

NHC-CuI by ICP-Mass

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Determine CuI contents of Au(SR)(IL)(ILCu) (6)

I

H3COH

H

HH

S

N

SAu

CH3

N

CuCl

HH

Au(SR)0.09(ILCu)1(6)

2H2H 2H

3H

ILCu : iodoanisole = (1-0.1648) : 0.1648 = Cu : 2.245 x 10-6

Cu = 4.068 x 10-6 molILCu : SR = 0.8352 : 0.1080 = 1:0.13

d6-DMSO

Au(SR)(ILCu) 8 mg

4-iodoanisole

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+N3N

NN

NHC-CuI Catalysis Huisgen Cycloaddition

Condition: Benzyl azide = 2 mmol, phenyl acetylene = 2.4 mmol. solvent = 0.5 mL. Yield determined by 1H NMR. (a) conversion is traced. (b) conversion is detected after reaction quenched. (c) 20 hr. (d) 16 h

r

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Using Microwave System to Catalysis Huisgen Cycloaddition

microwave thermal

Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250-6284.

Solvent Time(min) Conversion (%)

[Bmim][Br] 0.5 65

DMSO

1.5 4

2 24

3 99

CH3CN0.5 8

1 54

+

N3

1 mol % Au(SR)0.19(IL)0.57(ILCu)1 (6)

600 W

NN

N

Conditions: Benzyl azide (0.8 mmol), alkyne (0.96 mmol), Solvent = 0.15 mL. Conversion detected by 1H NMR

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Conclusions

We have successful synthesis Complex 6 , and characterized by 1H- and 13C-NMR, TEM, IR, EDS and XPS.

We have successfully demonstrated the catalytic activity of the CuI complex for theHuisgen cycloaddition.

In the future, we would try to use Au-NHC-CuI

for the recycling test on Huisgen cycloaddition.

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Department of Chemistry & Biochemistry Chung Cheng University