An Easily Accessible Resin-Supported Palladium Catalyst for Sonogashira Coupling

Abstract

Readily available aminomethyl-polystyrene beads can be transformed in a one-pot reaction to an air-stable polymer-bound chelate phosphine, which can be used for the immobilization of homogeneous catalysts. Such prepared Pd catalysts have proven to be useful reagents for mediating Sonogashira-coupling reactions.

Key words

combinatorial chemistry - catalyst - cross-coupling - solid-phase - palladium

References

• For leading reviews see:
• 1a Kirschnig A. Monenschein H. Wittenberg R. Angew. Chem. Int. Ed.  2001,  40:  650 
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• Recent reviews:
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• 2c de Miguel YR. Brule E. Margue RG. J. Chem. Soc., Perkin Trans. 1  2001,  3085 
• For example:
• 3a Mizugaki T. Murata M. Ooe M. Ebitani K. Kaneda K. Chem. Commun.  2002,  52 
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• 4a

  Reetz, M. T.; Becker, M. unpublished results.

• 4b Becker M. Diplomarbeit   Universität; Marburg: 1997. 
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• Parallel to our work the group of Uozumi has prepared amphiphilic Pd catalysts for Suzuki- and Heck-couplings using Argogel-NH₂ applying a similar strategy:
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6

General Experimental Procedure: All reactions are carried out under an atmosphere of argon using Schlenk-techniques. Aminomethyl-resin beads (1) are carefully degassed by swelling the beads in dry toluene and removing the solvent in vacuo (repeated 1×) (This procedure is necessary to avoid P(V) formation during the preparation of 3 due to trapped oxygen molecules in untreated 1. Meanwhile, a second Schlenk flask is charged with para-formaldehyde (4 equiv), dry MeOH and diphenylphosphine (4 equiv). This reaction mixture is heated to 60 °C until the white suspension forms a colorless solution. After removal of MeOH in vacuo the remaining viscous oil is diluted in dry toluene. This solution is added to the beads swollen in dry toluene. The reaction mixture is heated to 105 °C overnight. In the cooler regions of the flask the water-toluene azeotrope separates indicating the reaction progress. After cooling to r.t. the beads are collected by filtration under argon. The beads are washed extensively with dry toluene (4×), CH₂Cl₂/THF (1/1) (2×) and CH₂Cl₂ (2×). The beads are dried in vacuo until the weight remains constant. We have successfully applied this procedure for the preparation of 3 using several types of polystyrene resins (varying in grain size, degree of cross-linking, and loading), Tentagel-resin, and macroporous beads.

7

Experimental Procedure for Ligand Metathesis:
All reactions are carried out under an argon atmosphere using Schlenk-techniques. To polystyrene beads 3 (3 g, 2.31 mmol), swollen in 120 mL degassed CHCl₃, is added 1.1 equiv (COD)PdCl₂. The reaction mixture is heated at 60 °C for 26 h. After cooling to r.t. the beads are collected by filtration under argon. The beads are washed extensively with degassed CHCl₃ (4 × 40 mL), EtOH (1 × 40 mL) and dry CH₂Cl₂ (3 × 40 mL). The beads are dried in vacuo until the weight remains constant. Elemental analysis: 0.81% N, 3.22% P, 5.72% Pd (elemental analyses have been carried out by Mikroanalytisches Laboratorium H. Kolbe, Mülheim/Ruhr).

10

Representative Experimental Procedure: Synthesis of Diphenylacetylene ( 7a): In a light protected Schlenk-flask polystyrene-supported Pd-catalyst 4 (44.2 mg, 0.024 mmol Pd) was allowed to swell 5 min under argon atmosphere in degassed 1,4-dioxane: piperidine (2:1) (15 mL). Iodobenzene (5a) (1.5 mmol, 306.3 mg), phenylacetylene (6a) (2.1 mmol, 214.8 mg) and copper(I)iodide (0.03 mmol, 5.8 mg) were added to the catalyst. The mixture was slowly stirred under argon at 60 °C for 2 h. The Pd-beads were separated from the mixture by filtration and washed with CH₂Cl₂ (4 × 20 mL). The solution was washed with a sat. solution of ammonium chloride (1 × 30 mL) (this extractive step removes Cu-impurities by formation of the water soluble Cu-tetraamine complex) and the aqueous layer was extracted with CH₂Cl₂ (2 × 15 mL). The combined organic layers were dried over Na₂SO₄ and the solvent removed in vacuo. Purification by flash chromatography (SiO₂, pentane) provided 265.2 mg 7a (99%, colorless crystals).

11

Polymeric bound Pd catalyst 4 can be stored for several months without any significant loss of activity (Schlenk flask, argon, 4 °C).