9-bromo-9-borabicyclo[3.3.1]nonane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (5-Bromo-2-methoxyphenyl)(2,6-difluoro-5-(tributylstannyl)pyridin-3-yl)methanone (6.48 g, 10.50 mmol) was dissolved in DCM (60 mL) under nitrogen and cooled in a dry ice bath to −78° C. 9-Bromo-9-borabicyclo[3.3.1]nonane, (1 M in DCM, 11.02 mL, 11.02 mmol) was added dropwise over 5 minutes and the reaction stirred for another 5 minutes. The flask was removed from the cold bath and stirred at ambient temperature for 20 minutes then saturated sodium bicarbonate (50 mL) was added to quench. Water (200 mL) and dichloromethane (100 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to dichloromethane gradient) gave 7-bromo-2-fluoro-3-(tributylstannyl)-5H-chromeno[2,3-b]pyridin-5-one. The flask was removed from the cold bath stirred at ambient temperature for 20 minutes saturated sodium bicarbonate (50 mL) was added to quench Water (200 mL) and dichloromethane (100 mL) were added the phases mixed separated The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure Purification

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (5-Bromo-2-methoxyphenyl)(2,6-difluoro-5-(tributylstannyl)pyridin-3-yl)methanone (6.48 g, 10.50 mmol) was dissolved in DCM (60 mL) under nitrogen and cooled in a dry ice bath to −78° C. 9-Bromo-9-borabicyclo[3.3.1]nonane, (1 M in DCM, 11.02 mL, 11.02 mmol) was added dropwise over 5 minutes and the reaction stirred for another 5 minutes. The flask was removed from the cold bath and stirred at ambient temperature for 20 minutes then saturated sodium bicarbonate (50 mL) was added to quench. Water (200 mL) and dichloromethane (100 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to dichloromethane gradient) gave 7-bromo-2-fluoro-3-(tributylstannyl)-5H-chromeno[2,3-b]pyridin-5-one. The flask was removed from the cold bath stirred at ambient temperature for 20 minutes saturated sodium bicarbonate (50 mL) was added to quench Water (200 mL) and dichloromethane (100 mL) were added the phases mixed separated The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure Purification

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (5-Bromo-2-methoxyphenyl)(2,6-difluoro-5-(tributylstannyl)pyridin-3-yl)methanone (6.48 g, 10.50 mmol) was dissolved in DCM (60 mL) under nitrogen and cooled in a dry ice bath to −78° C. 9-Bromo-9-borabicyclo[3.3.1]nonane, (1 M in DCM, 11.02 mL, 11.02 mmol) was added dropwise over 5 minutes and the reaction stirred for another 5 minutes. The flask was removed from the cold bath and stirred at ambient temperature for 20 minutes then saturated sodium bicarbonate (50 mL) was added to quench. Water (200 mL) and dichloromethane (100 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to dichloromethane gradient) gave 7-bromo-2-fluoro-3-(tributylstannyl)-5H-chromeno[2,3-b]pyridin-5-one. The flask was removed from the cold bath stirred at ambient temperature for 20 minutes saturated sodium bicarbonate (50 mL) was added to quench Water (200 mL) and dichloromethane (100 mL) were added the phases mixed separated The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure Purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,2,3,4-tetrahydro-1,4-epoxynaphthalene (2.92 g, 20 mmol) and triethylamine (0.3 mL, 2 mmol) in 40 mL of dichloromethane at 0° C. was added 9-bromo-9-borabicyclo[3.3.1]nonane (1 M solution in tetrahydrofuran, 30 mL, 30 mmol). The reaction mixture was stirred at 0° C. for 20 minutes, and a 2 M solution of methylamine in tetrahydrofuran (40 mL) was then added, forming a white precipitate. The reaction mixture was stirred at room temperature for 16 h, poured into 100 mL of 1 M aqueous hydrochloric acid, and filtered. The filtered aqueous layer was washed with dichloromethane, basified with NaOH pellets to pH 13, and then extracted with dichloromethane. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuo to give a gummy yellow solid. The solid was slurried in diethyl ether, filtered, washed with diethyl ether and air dried to give 2.15 g of the title compounds as white powder. forming a white precipitate The reaction mixture was stirred at room temperature for 16 h filtered The filtered aqueous layer was washed with dichloromethane extracted with dichloromethane The extract was washed with brine dried over magnesium sulfate evaporated in vacuo to give a gummy yellow solid filtered washed with diethyl ether and air dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9-bromo-9-bora-bicyclo[3.3.1]nonane 1 M in DCM (33 mL, 33 mmol) at 0° C. was added ethynylcyclohexane (3.6 mL, 28 mmol) under argon via syringe slowly dropwise in portions over 10 min. The reaction mixture was allowed to stir 3 h, at which point acetic acid (4.8 mL, 83 mmol) was added dropwise in portions over 20 min. After 1 h additional, sodium hydroxide (17 mL, 166 mmol) was added slowly, followed by cautious addition of hydrogen peroxide (8.5 mL, 83 mmol). The reaction mixture was allowed to stir rapidly 1 h, then was warmed to ambient temperature. The reaction mixture was partitioned between hexanes and water, and the organic layer was washed with saturated aq. Sodium bicarbonate, and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting liquid was filtered through a 3 cm pad of silica gel, rinsing with 200 mL hexanes, and the filtrate was concentrated in vacuo to give crude (1-bromovinyl)-cyclohexane as a clear/colorless oil which was used without further purification. was added dropwise in portions over 20 min The reaction mixture was partitioned between hexanes and water the organic layer was washed with saturated aq. Sodium bicarbonate, and brine dried over sodium sulfate filtered concentrated in vacuo The resulting liquid was filtered through a 3 cm pad of silica gel rinsing with 200 mL hexanes the filtrate was concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (5-Bromo-2-methoxyphenyl)(2,6-difluoro-5-(tributylstannyl)pyridin-3-yl)methanone (6.48 g, 10.50 mmol) was dissolved in DCM (60 mL) under nitrogen and cooled in a dry ice bath to −78° C. 9-Bromo-9-borabicyclo[3.3.1]nonane, (1 M in DCM, 11.02 mL, 11.02 mmol) was added dropwise over 5 minutes and the reaction stirred for another 5 minutes. The flask was removed from the cold bath and stirred at ambient temperature for 20 minutes then saturated sodium bicarbonate (50 mL) was added to quench. Water (200 mL) and dichloromethane (100 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to dichloromethane gradient) gave 7-bromo-2-fluoro-3-(tributylstannyl)-5H-chromeno[2,3-b]pyridin-5-one. The flask was removed from the cold bath stirred at ambient temperature for 20 minutes saturated sodium bicarbonate (50 mL) was added to quench Water (200 mL) and dichloromethane (100 mL) were added the phases mixed separated The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure Purification