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entree SiliaCat

Heck Coupling Using SiliaCat DPP-Pd & S-Pd

The Heck reaction, also known as the Mizoroki-Heck reaction, is the coupling of a halide with an alkene in the presence of a base and a palladium catalyst. This coupling allows a substitution reaction on alkenes and is of great importance in pharmaceutical research. We determined that the best catalyst for this reaction is SiliaCat DPP-Pd. It showed good reactivity for aryl iodides, bromides and chlorides.

Note: SiliaCat Pd0 results were not available at the time of printing. Contact us for details.

Base and Solvent Effects

The Heck coupling between iodobenzene and styrene was used to evaluate the influence of solvent and base. The best combinations are KOAc/DMF, Et3N/MeCN and Pr3N/neat. Using these systems, high yields and great selectivity in favor of product A were obtained.

HeckCouplingReaction.gif

Base and Solvent Effects (SiliaCat DPP-Pd)
SiliaCat
(mol %)
Base
Solvent
(0.4 M)
Time
(h)
Conversion
A / B / C (%)
0.5
KOAc
DMF
24
100 (90 / 9.5 / 0.5)
0.5
Na2CO3
DMF
24
67 (62 / 47 / 0)
0.1
Et3N
MeCN
24
93 (77 / 6 / 11)
0.1
Et3N
H2O
24
75 (70 / 5 / 0)
0.1
Pr3N
(neat)
20
100 (95 / 5 / 0)

 

Catalytic Performance and Comparison vs Homogeneous Catalyst

SiliaCat DPP-Pd is a very efficient catalyst for the Heck coupling and allows greater selectivity over homogeneous Pd catalyst (TPP is required). In addition to higher yield of the desired product, the catalyst left minimal residual Pd, TPP or TPPO in solution that would have otherwise required the use of a metal scavenger, chromatography or trituration to remove.

HeckCouplingReactionArylHalide

Catalytic Performance and Comparaison vs Homogeneous
Substrate
SiliaCat DPP-Pd
(mol %)
Base
Solvent
(0.4 M)
Conversion
A / B / C (%)
Phosphine Leaching (ppm)
R
X
4-CN
Br
0.25
NaOAc
DMF
100 (95 / 5 / -)
-
4-NO2
Br
0.25
NaOAc
DMF
99 (97 / 2 / -)
-
2-CH3
Br
0.25
Et3N
MeCN
71 (67 / 5 / -)
-
4-OMe
I
0.25
Et3N
MeCN
75 (60 / 15 / -)
-
H
I
0.1
Et3N
MeCN
100 (98 / 2 / -)
0
H
I
1.0 Pd(OAc)2 PPh3
Et3N
MeCN
100 (70 / 22 / 8)
6,030

 

Substrate Scope, Leaching and Microwave Compatibility

SiliaCat catalysts are efficient in the Heck coupling with different substrates. In all cases, conversion and selectivities were excellent. Leaching results were all below FDA regulations, and no further metal removal was needed. Microwave technology allows faster kinetics with good yields.

HeckCouplingReactionArylHalide

Substrate Scope, Leaching and Microwave (MW) Compatibility
Rn
Mode
SiliaCat DPP-Pd
SiliaCat S-Pd
mol %
Time
Temp
Conv. / Sel. (%)
Leaching (ppm)
mol %
Time
Temp
Conv. / Sel. (%)
Leaching (ppm)
1
Batch
0.5
24 h 120°C
100 / 97
-
0.5
24 h 120°C
98 / 92
-
MW
0.2
10 m 125°C
93 / 85
P: 0.3, Pd: 0.02, Si: 0.8
0.2
15 m 125°C
97 / 93
Pd: 3.8, Si: 1.9
2
Batch
0.2
24 h 135°C
100 / 98
-
0.25
24 h 120°C
85 / 75
-
MW
0.2
0.5
10 m
30 m1
125°C
150°C
92 / 81
99 / 931
-
P: 0.7, Pd: 0.02, Si: 1.6
0.2
15 m 125°C
87 / 76
Pd: 0.3, Si: 0.8

 

Heck 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 (MeCN) or to 120°C (DMF or NMP) and after 10 minutes (when solution is homogeneous) add the desired quantity of catalyst.

Microwave Conditions

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

  • Power: 100 W (I-) or 200 W (Br-, Cl-)
  • Pressure: 150 psi (I-) or 200 psi (Br-, Cl-)
  • Temperature: 100°C (I-) or 125°C (Br-, Cl-)
  • Reaction Time: 10 min (I-) or 15 min (Br-, Cl-)

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.

Heck Coupling Typical Experimental Conditions
Products
Conventional Conditions for 1 eq of:
Microwave Conditions for 1 eq of:
Ar-Iodide
Ar-Bromide
Ar-Chloride
Ar-Iodide
Ar-Bromide
Ar-Chloride
Base
1.5 eq.
[Et3N or NaOAc]
1.5 eq.
[NaOAc]
1.5/0.5 eq.
[Ca(OH)2/TBAB]
1.5 eq.
[Et3N or NaOAc]
1.5 eq.
[K2CO3]
2.0 eq.
[K2CO3]
Olefin
1.2 eq.
1.2 - 2.0 eq.
1.2 - 2.0 eq.
1.2 - 2.0 eq.
1.2 - 2.0 eq.
1.2 - 2.0 eq.
SiliaCat Catalyst
≥ 0.5 mol %
≥ 0.5 mol %
≥ 1.0 mol %
≥ 0.2 mol %
≥ 0.2 mol %
≥ 1.0 mol %
Best Solvents
(HPLC Grade)
MeCN (1.2 M)
DMF (0.75 M)
DMF
(0.75 - 1.5 M)
NMP/H2O
(1:1, 1.67 M)
MeOH
(0.2 M)
MeOH
(0.2 M)
EtOH/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

    The significant costs associated with precious metal catalysts and their undesired tendency to remain in organic products has generated interest for an increase in reactivity and ways to recover and reuse these metals. SiliaCat DPP-Pd is a unique diphenylphosphine palladium (II) heterogeneous catalysts made from a leach-resistant organoceramic matrix.
  2. SiliaCat® Heterogeneous Catalysts TEMPO

    SiliaCat® Heterogeneous Catalysts TEMPO

    SiliaCat® TEMPO is a heterogeneous catalyst/reagent made from a proprietary class of organosilica-entrapped radicals suitable for the selective oxidation of delicate substrates into valued carbonyl derivatives.

  3. SiliaCat® Heterogeneous Catalysts Pd0

    SiliaCat® Heterogeneous Catalysts Pd0

    SiliaCat Pd0 is a new series of patent-protected sol–gel-entrapped Pd nanocatalysts. It is made from highly dispersed Pd nanoparticles (uniformly in the range 4.0–6.0 nm) encapsulated within an organosilica matrix.
  4. SiliaCat® Heterogeneous Catalysts Pt0

    SiliaCat® Heterogeneous Catalysts Pt0

    SiliaCat Pt0 is made of organosilica physically doped with nanostructured platinum (0), and is both stable and efficient. This catalyst was successfully prepared by a novel and simple sol-gel route.
  5. SiliaCat® complete heterogeneous catalysts kit

    SiliaCat® complete heterogeneous catalysts kit

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

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