Rhodium(i)-catalyzed C6-selective C–H alkenylation and polyenylation of 2-pyridones with alkenyl and conjugated polyenyl carboxylic acids

A versatile Rh(i)-catalyzed C6-selective decarbonylative C–H alkenylation of 2-pyridones with readily available alkenyl carboxylic acids has been developed.


S8
To an oven-dried pressure tube were sequentially added 1a (34.6 mg, 0.2 mmol), [Rh(CO)2Cl]2 (0.8 mg, 1.0 mol%), 2a (32.6 mg, 0.22 mmol), Boc2O (65.5 mg, 0.3 mmol) and 1,4-dioxane (2.0 mL). The tube was sealed, and the reaction mixture was heated and stirred vigorously at 130 o C for 6 h in an oil bath under air atmosphere. The reaction tube was removed from the oil bath and cooled to room temperature. The reaction mixture was washed with saturated sodium bicarbonate solution (5 mL) and extracted with CH2Cl2 (5 mL × 3). The combined organic layer was dried over Na2SO4, filtered and evaporated under vacuum. The crude residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane to give the purified product.

Synthetic applications (a) Gram-scale synthesis of 3aa
To a 100 mL round-bottom flask were added 1a (1.03 g, 6.0 mmol), [Rh(CO)2Cl]2 (23.4 mg, 1.0 mol%), 2a (978.0 mg, 6.6 mmol), Boc2O (1.96 g, 9.0 mmol) and 1,4dioxane (25 mL). The flask was sealed, and the reaction mixture was heated and stirred vigorously at 130 o C for 6 h in the oil bath under air atmosphere. The flask was next removed from the oil bath and cooled to room temperature. The mixture was washed with saturated sodium bicarbonate solution (50 mL) and extracted with CH2Cl2 (25 mL × 3). The combined organic layer was dried over Na2SO4, filtered and evaporated under vacuum. The crude residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexanes (hexanes/ethyl acetate = 1/2) to give pure 3aa (1.45g, 88% yield).

S11
To an oven-dried pressure tube were sequentially added 1a (51.7 mg, 0.3 mmol), [Rh(CO)2Cl]2 (1.2 mg, 1.0 mol%), D2O (30.0 mg, 1.5 mmol), Boc2O (98.2 mg, 0.45 mmol) and 1,4-dioxane (3.0 mL). The tube was sealed, and the reaction mixture was heated and stirred vigorously at 130 o C for 1 h in an oil bath under air atmosphere. Then the tube was removed from the oil bath and cooled to room temperature. After removal of the volatile materials under reduced pressure, the crude residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane to give an inseparable mixture of 1a (62%) and [D]-1a (38%). The ratio of H/D was determined on the basis of 1 H NMR analysis.
To an oven-dried pressure tube were sequentially added 1a (51.7 mg, 0.3 mmol), [Rh(CO)2Cl]2 (1.2 mg, 1.0 mol%), 2a (48.9 mg, 0.33 mmol), D2O (30.0 mg, 1.5 mmol), Boc2O (98.2 mg, 0.45 mmol) and 1,4-dioxane (3.0 mL). The tube was sealed, and the reaction mixture was heated and stirred vigorously at 130 o C for 1 h in the oil bath under air atmosphere. Then the tube was removed from the oil bath and cooled to room temperature. The mixture was washed with saturated sodium bicarbonate solution (15 mL) and extracted with CH2Cl2 (5 mL x 3). The combined organic layer was dried over Na2SO4 and filtered. The volatile materials were removed under reduced pressure and the crude residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (hexanes/ethyl acetate = 1/2) to give 3aa (32.1 mg, 39%) and an inseparable mixture of 1a and [D]-1a (27.7 mg, 53%). The ratio of H/D was determined on the basis of 1 H NMR analysis.
b) The coupling reaction of anhydride 11 with 1a To an oven-dried pressure tube were sequentially added 1a (51.7 mg, 0.3 mmol), [Rh(CO)2Cl]2 (1.2 mg, 1.0 mol%), 11 (91.8 mg, 0.33 mmol) and 1,4-dioxane (3.0 mL). The tube was sealed, and the reaction mixture was heated and stirred vigorously at 130 o C in an oil bath. After 6 h, the tube was removed from the oil bath, and cooled to room temperature. The volatiles were removed, and the crude residual was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (hexanes/ethyl acetate = 1/2) to give pure 3aa (74.9 mg, 91%).

c) The in situ generation of anhydride 11
A mixture of equimolar amounts of 2a (32.6 mg, 0.22 mmol) and Boc2O (65.5 mg, 0.3 mmol) in 1,4-dioxane (2.0 mL) was stirred at 130 o C for 6 h. After cooling to room temperature, the volatile materials were removed under reduced pressure and the crude residual was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (hexanes/ethyl acetate = 2/1) to give cinnamic anhydride 11 (52.0 mg, 85%). Cinnamic anhydride (11