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
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Parallel to our work the group of
Uozumi has prepared amphiphilic Pd catalysts for Suzuki- and Heck-couplings using
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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).
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Palladium Reagents: Innovations in Organic Synthesis
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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).
