2-Allylsulfonyl Pyridines for Cross Coupling

　The use of pyridine derivatives in efficient C-C cross-coupling processes is useful in medicinal chemistry, and reactions using pyridine sulfinates have been reported.¹⁾ Allylsulfonyl pyridines (1,2,3) are reagents improved by Willis et al.²⁾ Since these reagents function as potential pyridine sulfinate salts, they react with aryl halides to give 2-pyridylarenes by the palladium-catalyzed C-C cross-coupling reaction. It is also possible to convert another functional group of the pyridine ring because the allylsulfonyl group is more stable against general synthetic transformations than pyridine sulfinates.

TCI Practical Example: Cross-coupling reaction using 3 as a nucleophile
To a pressure resistant test tube was charged with 3 (592 mg, 3.0 mmol, 1.5 equiv.), palladium(II) acetate (22 mg, 0.1 mmol, 5 mol%), P^tBu₂Me·HBF₄ (50 mg, 0.2 mmol, 10 mol%), cesium carbonate (1.30 g, 4.0 mmol, 2.0 equiv.). The test tube was purged with nitrogen and DMF (10 mL) and 4-bromoanisole (0.25 mL, 2.0 mmol, 1.0 equiv.) were added in one portion at room temperature. The resulting mixture was stirred at 150 °C for 17 h. The reaction mixture was cooled to room temperature and quenched with water (10 mL). The organic layer was extracted with diethyl ether (100 mL x 3), dried with Na₂SO₄ (20 g) and then concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (ethyl acetate:hexane = 5:95 - 18:82) to afford the corresponding compound 4 as yellow solid (196 mg, 49%).

References

• 1) Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides
• T. Markovic, B. N. Rocke, D. C. Blakemore, V. Mascitti, M. C. Willis, Chem. Sci. 2017, 8, 4437.
• 2) Heterocyclic Allylsulfones as Latent Heteroaryl Nucleophiles in Palladium-Catalyzed Cross-Coupling Reactions
• T. Markovic, P. R. D. Murray, B. N. Rocke, A. Shavnya, D. C. Blakemore, M. C. Willis, J. Am. Chem. Soc. 2018, 140, 15916.

Related Products

P2161

Palladium(II) Acetate (Purified)

D4731

Di-tert-butyl(methyl)phosphonium Tetrafluoroborate (= P^tBu₂Me·HBF₄)

C2160

Cesium Carbonate

B0547

4-Bromoanisole

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