Comparing the Reactivity of the 4- and 5-Positions of 2-Phenylthiazoles in Stille Cross-Coupling Reactions

Abstract

A systematic study of the cross-coupling capability of 4- and 5-substituted 2-phenylthiazoles under Stille conditions is presented. Two cross-coupling options were investigated: 1) combination of thiazolylstannanes with various aryl(hetaryl) halides and, 2) reaction of halothiazoles with PhSn(Bu)₃ as coupling partner. The results obtained from the cross-coupling reactions on the 4- and 5-positions of the thiazole system were compared regarding the influence of the position of the halide (Br, I) and the Bu₃Sn group on both coupling partners. A broad selection of aromatic and heteroaromatic halides was coupled in order to establish a general reactivity platform for this heterocyclic system.

Key words

cross-coupling - heterocycles - thiazoles - palladium - Stille reaction

References and Notes

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14

Typical Experimental Procedure: A solution of 3 (1 equiv, 200 mg, 0.44 mmol), iodobenzene (1.1 equiv, 100 mg, 0.49 mmol), Pd(PPh₃)₄ (0.05 equiv, 25 mg, 0.02 mmol) and CsF (2.2 equiv, 148 mg, 0.98 mmol) in toluene (12 mL) was refluxed for 2 h under nitrogen. The reaction mixture was filtered over Celite^® and evaporation of the solvent in vacuo gave a residue, which was purified by column chromatog-raphy (silica gel, PE-EtOAc, 10:1) to give 2,5-di-phenyl-thiazole (6a; 82mg, 78%) as a colorless solid. All characteri-zation data of the obtained product were in agreement with those given in the literature.¹⁶