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Development of Pd/C-Catalyzed Cyanation of Aryl Halides

Reaction Scheme

Abstract

An orthogonal set of catalyst systems has been developed for the Suzuki?Miyaura coupling of 3,3-disubstituted and 3-monosubstituted allylboronates with (hetero)aryl halides. These methods allow for the highly selective preparation of either the ?- or the ?-isomeric coupling product.

Substrates

Procedure

Procedure 1: A screw-cap test tube, which was equipped with a magnetic stir bar and fitted with a teflon septum, was charged with [(allyl)PdCl]2 (5.5 mg, 0.015 mmol) and L6 (25.5 mg, 0.06 mmol). If the (hetero)aryl halide (1.0 mmol) was a solid, it was also added at this time. The test tube was evacuated and backfilled with argon (this process was repeated a total of 3 times). Allylboronic acid pinacol ester (1.2 mmol, 1.2 equiv) was added via syringe. If the (hetero)aryl halide was a liquid, it was added to the test tube via syringe at this time. Acetonitrile (2 mL) and aqueous K3PO4 solution (2.5 M) were added via syringe and the reaction mixture was allowed to stir at 70 �C for 12 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (5 mL). The aqueous layer was extracted with ethyl acetate (2�10 mL). The combined organic layers were dried over MgSO4, concentrated in vacuo, and purified with the aid of a Biotage SP4 instrument. Procedure 2: A screw-cap test tube, which was equipped with a magnetic stir bar and fitted with a teflon septum, was charged with [(allyl)PdCl]2 (3.4 mg, 0.010 mmol) and L3 (17.2 mg, 0.04 mmol). If the (hetero)aryl halide (1.0 mmol) was a solid, it was also added at this time. The test tube was evacuated and backfilled with argon (this process was repeated a total of 3 times). Allylboronic acid pinacol ester (1.2 mmol, 1.2 equiv) was added via syringe. If the (hetero)aryl halide was a liquid, it was added to the test tube via syringe at this time. THF (2 mL) and aqueous K3PO4 solution (2.5 M) were added via syringe and the reaction mixture was allowed to stir at 40 or 60 �C for 12 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (5 mL). The aqueous layer was extracted with ethyl acetate (2�10 mL). The combined organic layers were dried over MgSO4, concentrated in vacuo, and purified with the aid of a Biotage SP4 instrument.

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