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entree SiliaCat

Sonogashira Coupling Using SiliaCat Catalysts

The Sonogashira coupling reaction of aryl halides and terminal acetylenes is an effective method for the formation of substituted acetylenes. This reaction is frequently utilized as a key step in natural product chemistry and for the synthesis of acetylene compounds, which have several applications.

Catalyst Concentration and Solvent Effects

Sonogashira coupling between iodonitrobenzene and phenylacetylene was achieved easily and without the need for co-catalysts to activate the alkyne, making the use of SiliaCat an efficient method for the formation of substituted acetylenes. All catalysts screened presented excellent efficiency, even in low amounts.

Catalyst Concentration and Solvent Effects
SiliaCat DPP-Pd
SiliaCat S-Pd
SiliaCat Pd0
mol %
Solvent
(M)
Time
(min)
Conv.
(%)
TON
(TOF)
mol %
Solvent
(M)
Time
(min)
Conv.
(%)
TON
(TOF)
mol %
Solvent
(M)
Time
(min)
Conv.
(%)
TON
(TOF)
0.5
EtOH/H2O
(0.07)
30 m
100
200
(400)
0.5
EtOH/H2O
(0.07)
5 m
100
200
(2,500)
0.1
EtOH
(0.1)
2 h
100
1,000
(500)
0.5
MeOH/H2O
(0.07)
5 m
100
200
(2500)
0.5
MeOH/H2O
(0.07)
1 h
100
200
(200)
0.1
EtOH
(0.05)
30 m
100
1,000
(2,000)
0.1
EtOH/H2O
(0.07)
1 h
100
1,000
(1,000)
0.1
EtOH/H2O
(0.07)
1 h
100
1,000
(1,000)
 
0.1
MeOH/H2O
(0.07)
15 m
100
1,000
(4,000)
 
0.01
EtOH/H2O
(0.13)
3 h
100
10,000
(4,000)
0.002
EtOH/H2O
(0.13)
8 h
100
50,000

 

Iodo-Substrate Scope and Microwave Compatibility

Sonogashira couplings between iodoaryls and phenylacetylene are achieved with ease and without the need for co-catalysts to activate the alkyne.This shows that SiliaCat is an efficient tool for the formation of substituted acetylenes.

SonogashiraParallelReaction

 

Iodo-Substrate Scope and Microwave Compatibility
R
Mode
SiliaCat DPP-Pd
SiliaCat S-Pd
SiliaCat Pd0
mol % Conditions
Conv. / Sel. (%)
mol %
Conditions
Conv. / Sel. (%)
mol %
Conditions
Conv. / Sel. (%)
4-NO2
Batch
1
EtOH (0.08 M)
77°C, 4 h
100 / 100
1
EtOH (0.08 M)
77°C, 4 h
100 / 100
1
EtOH (0.08 M)
77°C, 4 h
100 / 100
MW
0.6
MeOH/H2O (0.2 M)
100°C, 2 min
100 / -
0.6
MeOH/H2O (0.2 M)
100°C, 2 min
100 / -
0.1
MeOH (0.1 M)
75°C, 5 min
100 / -
4-OMe
Batch
1
EtOH (0.08 M)
77°C, 4 h
99 / 98
1
EtOH (0.08 M)
77°C, 4 h
100 / 100
1
EtOH (0.08 M)
77°C, 4 h
99 / 98
4-CH3
Batch
1
EtOH (0.08 M)
77°C, 4 h
100 / 100
1
EtOH (0.08 M)
77°C, 4 h
100 / 99
1
EtOH (0.08 M)
77°C, 4 h
100 / 100
MW
0.5
MeOH/H2O (0.2 M)
100°C, 2 min
90 / -
1
MeOH/H2O (0.2 M)
100°C, 2 min
88 / -
0.1
MeOH (0.2 M)
75°C, 5 min
100 / -

 

Bromo-Substrate Scope and Microwave Compatibility

SiliaCat DPP-Pd and Pd0 are also efficient catalysts for use with bromo substrates. A few examples of the Sonogashira coupling between various bromoaryls substrates (1 eq.) and phenylacetylene (1.25 eq.) using K2CO3 (2 eq.) in MeOH (0.2 M) are shown below. Conversions obtained with 1 mol % of SiliaCat DPP-Pd under microwave irradiation are presented below. Conventional methodology is also possible, but kinetics are significantly lower (a few hours compared to 15 minutes).

Bromo- Substrate Scope Conversion (%) Results using SiliaCat DPP-Pd

ParallelSubstrat11.gif

 

Sonogashira Coupling Typical Experimental Procedure

Conventional Experimental Conditions

Reaction - All products except the catalyst are added to a round bottom flask equipped with a condenser and a magnetic stirrer. Bring mixture to reflux, and after 10 minutes (when the solution is homogeneous) add the required quantity of catalyst.

Microwave Conditions

Reaction - All products are added to a microwave tube equipped with a magnetic stirrer. Set microwave conditions to:

  • Power: 150 W (I-) or 200 W (Br-)
  • Pressure: 150 psi (I-) or 200 psi (Br-)
  • Temperature: 100°C (I-) or 100 - 150°C (Br-)
  • Reaction Time: 5 - 15 min (I-) or 5 - 20 min (Br-)

Work-up

Once the reaction is complete (determined by TLC or GC-MS), follow the same work-up procedure as for Suzuki coupling conventional experimental conditions as they are applicable to microwave conditions.

Sonogashira Coupling Typical Experimental Conditions
Products
Standard Conditions for 1 eq of:
Microwave Conditions for 1 eq of:
Ar-Iodide
Ar-Bromide
Ar-Iodide
Ar-Bromide
Base [K2CO3]
1.5 eq.
1.5 eq.
1.5 eq.
2.0 eq.
Alkyne
1.1 eq.
1.25 eq.
1.10 eq.
1.5 eq.
SiliaCat Catalyst
≥ 0.5 mol %
≥ 1.0 mol %
≥ 0.5 mol %
≥ 1.0 mol %
Best Solvents
(HPLC Grade)
For room temperature reaction: MeOH (0.02 M)
For reflux reaction: MeOH (0.05 - 0.13 M, typ.: 0.07 M)
or EtOH/H2O (10:1, 0.1 M)
MeOH
(0.2M)
MeOH/H2O
(10:1, 0.2 M)
*Note: molar concentration is related to the substrate.

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  1. SiliaCat DPP-Pd heterogeneous catalyst

    SiliaCat® Heterogeneous Catalysts DPP-Pd

    Typical Applications: Suzuki, Heck, Sonogashira, Kumada, Stille and Buchwald amination
  2. SiliaCat® Heterogeneous Catalysts TEMPO

    SiliaCat® Heterogeneous Catalysts TEMPO

    Typical Applications: Oxidation of alcohols or Aldehydes
  3. SiliaCat® Heterogeneous Catalysts Pd0

    SiliaCat® Heterogeneous Catalysts Pd0

    Typical Applications: Suzuki, Heck Sonogashira, Kumada, Stille, Selective debenzylation, Selective hydrogenation
  4. SiliaCat® Heterogeneous Catalysts Pt0

    SiliaCat® Heterogeneous Catalysts Pt0

    Typical Applications: Selective reduction of nitroarenes, Hydrosilylation
  5. SiliaCat® complete heterogeneous catalysts kit: SiliaCat DPP-Pd, SiliaCat Pd0, SiliaCat Pt0 and SiliaCat TEMPO

    SiliaCat® complete heterogeneous catalysts kit

    Containing SiliaCat DPP-Pd, SiliaCat Pd0, SiliaCat Pt0 and SiliaCat TEMPO

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