A dual catalytic strategy for carbon–phosphorus cross-coupling via gold and photoredox catalysis

A new method for the P-arylation of aryldiazonium salts with H-phosphonates via dual gold and photoredox catalysis is described.


General Information.
Unless otherwise noted, reagents were obtained from commercial sources and used without further purification. All reactions were carried out under N 2 using sealed vial, unless otherwise stated. Dried DMF and THF were obtained by passage through activated alumina columns under argon. Dried acetonitrile was distilled over calcium hydride and stored over 4Å molecular sieves. All other dried solvents used in the reaction were obtained by storage over 3Å or 4Å molecular sieves. TLC analysis of reaction mixtures was performed on Merck silica gel 60 F254 TLC plates and visualized by UV. Preparative TLC was carried out on the same plates. Flash chromatography was carried out with ICN SiliTech 32-63 D 60 Å silica gel. 1 H spectra were recorded with Bruker AV-300 or AVQ-400. 13 C NMR spectra were recorded with Bruker DRX-500 or AV-600. 31 P NMR and 19 F NMR spectra were recorded with Bruker AVQ-400. Mass spectral and microanalytical data were obtained via the Micro-Mass/Analytical Facility operated by the College of Chemistry, University of California, Berkeley. The visible light used in reactions was provided by a standard household lamp with a 26 W fluorescent light bulb.

General procedure for P--arylation of H--phosphonate.
The H-phosphonate ester (0.1 mmol), Ph 3 PAuCl (0.01 mmol), Ru(bpy) 3 (PF 6 ) 2 (0.002 mmol) and aryldiazonium (0.3 mmol) were added to an oven-dried vial containing a stirring bar. The vial was fitted with a rubber septum. Anhydrous MeCN:EtOH (4:1) (0.5 ml) was added using a syringe in the absence of light, and then the mixture was degassed using freeze-pump-thaw for three cycles (freeze-pump-thaw: cooled to -78 o C and degassed via vacuum evacuation for 5 min, backfilled with nitrogen, and warm to room temperature). The reaction stirred with a 26 W household lamp (at 8-10 cm away from the light source) at the room temperature. After the reaction completed, the mixture was quenched with water and aqueous K 2 CO 3 solution. The mixture was extracted with DCM, dried with Na 2 SO 4 , filtered and concentrated in vacuum. The crude product was purified by column chromatography over silica gel using n-hexane and ethyl acetate.

General procedure for the synthesis of 3c (Large Scale).
The diethyl phosphite (3.0 mmol), Ph 3 PAuCl (8.0 mol%), Ru(bpy) 3 (PF 6 ) 2 (2 mol%) and p-methoxydiazonium (9.0 mmol) were added to an oven-dried vial containing a stirring bar. The vial was fitted with a rubber septum. Anhydrous MeCN:EtOH (4:1) (15 ml) was added using a syringe in the absence of light, and then the mixture was degassed using freeze-pump-thaw for three cycles (freeze-pump-thaw: cooled to -78 o C and degassed via vacuum evacuation for 5 min, backfilled with nitrogen, and warm to room temperature). The reaction stirred with a 26 W household lamp (at 8-10 cm away from the light source) at the room temperature. After the reaction completed, the mixture was quenched with water and aqueous K 2 CO 3 solution. The mixture was extracted with DCM, dried with Na 2 SO 4 , filtered and concentrated in vacuum. The crude product was purified by column chromatography

General procedure for P-arylation of phenyl phosphinic acid.
The phenyl phosphinic acid (0.1 mmol), Ph 3 PAuCl (0.01 mmol), Ru(bpy) 3 (PF 6 ) 2 (0.002 mmol) and aryldiazonium (0.3 mmol) were added to an oven-dried vial containing a stirring bar. The vial was fitted with a rubber septum. Anhydrous MeCN:ROH (R = Me or Et) (4:1) (0.5 ml) was added using a syringe in the absence of light, and then the mixture was degassed using freeze-pump-thaw for three cycles (freeze-pump-thaw: cooled to -78 o C and degassed via vacuum evacuation for 5 min, backfilled with nitrogen, and warm to room temperature). The reaction stirred with a 26 W household lamp (at 8-10 cm away from the light source) at the room temperature. After the reaction completed, the mixture was quenched with water and aqueous K 2 CO 3 solution. The mixture was extracted with DCM, dried with Na 2 SO 4 , filtered and concentrated in vacuum. The crude product was purified by column chromatography over silica gel using n-hexane and ethyl acetate.

One-pot synthesis of diethyl (4-fluorophenyl)phosphonate (3e).
An oven-dried vial was charged with BF 3 OEt 2 (0.33 mmol) in 0.6 ml of anhydrous THF at -15 o C, and then 4-fluoroaniline (0.3 mmol) was added. The vial was sealed and tert-butyl nitrite (0.39 mmol) was added dropwise via syringe to the rapidly stirred reaction mixture. After the addition, the mixture was maintained at -15 °C for 10 min and then allowed to warm to 0 °C for 30 min, and room temperature for a certain time which was detected by TLC. Then the reaction mixture was concentrated under reduced pressure. The residue was diluted with anhydrous MeCN:EtOH (4:1) (0.5 ml), and then diethyl phosphite (0.1 mmol), Ru(bpy) 3  (0.002 mmol) and aryldiazonium (0.3 mmol) were added in the absence of light. The mixture was degassed using freeze-pump-thaw for three cycles (freeze-pump-thaw: cooled to -78 ºC and degassed via vacuum evacuation for 5 min, backfilled with nitrogen, and warm to room temperature). The reaction stirred with a 26 W household lamp (at 8-10 cm away from the light source) at the room temperature. After 4h, the reaction mixture was quenched with water and aqueous K 2 CO 3 solution. The mixture was extracted with DCM, dried with Na 2 SO 4 , filtered and concentrated in vacuum. The crude product was purified by column chromatography over silica gel using n-hexane and ethyl acetate.

Chirality transfer of the diastereoenriched P(O)H compounds.
The diastereoenriched P(O)H compound was synthesis according to the literature. 4 The diastereoenriched P(O)H compound (0.1 mmol), Ph 3 PAuCl (0.01 mmol), Ru(bpy) 3 (PF 6 ) 2 (0.002 mmol) and aryldiazonium (0.3 mmol) were added to an oven-dried vial containing a stirring bar. The vial was fitted with a rubber septum. Anhydrous MeCN:EtOH (4:1) (0.5 ml) was added using a syringe in the absence of light, and then the mixture was degassed using freeze-pump-thaw for three cycles (freeze-pump-thaw: cooled to -78 o C and degassed via vacuum evacuation for 5 min, backfilled with nitrogen, and warm to room temperature). The reaction stirred with a 26 W household lamp (at 8-10 cm away from the light source) at the room temperature. After the reaction completed, the mixture was quenched with water and aqueous K 2 CO 3 solution. The mixture was extracted with DCM, dried with Na 2 SO 4 , filtered and concentrated in vacuum. The dr ratio of the 3w was determined by 31 P NMR.

Reaction Apparatus
Photochemical reaction was carried out under visible light irradiation by a PHILIPS 26 W fluorescent bulb (approximately 8-10 cm from the reaction) at room temperature.

Characterization data.
Some of the products are known compounds and the spectral data matched that previously reported [4][5][6][7] .