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Synlett 2007(8): 1251-1254  
DOI: 10.1055/s-2007-977457
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Emma Vickerstaffea, Anne-Laure Villarda, Mark Ladlowa, Steven V. Ley*b
a GlaxoSmithKline Cambridge Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
b Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
Fax: +44(1223)336442; e-Mail: svl1000@cam.ac.uk;
Further Information

Publication History

Received 7 March 2007
Publication Date:
08 May 2007 (online)

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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

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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.