Chromatography-Free Suzuki Reactions Using a Polymer-Assisted Solution-Phase (PASP) Approach

Abstract

An efficient Suzuki coupling protocol that affords reaction products in high purity without the need for chromatography or aqueous work-up is reported. The reaction, which utilises a combination of polymer-supported reagents, can be performed under thermal or microwave heating conditions and is particularly suited to parallel synthesis.

Key words

polymer-supported reagents - encapsulated palladium catalyst - microwave heating - Suzuki cross-coupling - parallel synthesis

References and Notes

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• 12 Microwave temperatures were measured externally to the reactor vial using the IR sensor fitted to the Emrys^® synthesiser. It is extremely unlikely that these values accurately reflect the significantly higher localised temperatures attained at the catalyst metal surface under microwave irradiation
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6

Standard solution-phase conditions employed for Suzuki coupling reaction: To a solution of 4-iodoanisole (1 mmol) and 4-tolylboronic acid (2 mmol) in DMF (10 mL) was added Na₂CO₃ (0.4 mmol), H₂O (2 mL) and Pd(OAc)₂EnCat™ (5 mol%, based on palladium content). The reaction mixture was stirred at 85 °C for 18 h.

7

MP-Carbonate was obtained from Sigma-Aldrich with a reported loading of 2.5-3.5 mmol/g.

10

Although the water present could be removed using anhydrous molecular sieves, a more reliable and pragmatic procedure proved to be co-evaporation prior to redissolution in DMF.