ethyl(diphenyl)phosphane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under an atmosphere of argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I)dichloride (6 mg; 0.009 mmol) and diphenylphosphinoethane (7 mg, 0.018 mmol) in dichloromethane (1 mL) was cooled to 0° C. and treated with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.174 mL, 1.2 mmol). After stirring for 30 min, a solution of tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)oct-7-enylcarbamate (120 mg, 0.3 mmol) in dichloromethane (4 mL) was added and the solution was stirred an additional 16 h. Dichloromethane (10 mL) was added, and the solution was washed successively with water and sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by column chromatography (3% methanol in dichloromethane) gave tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)octylcarbamate (142 mg, 90%). ESI MS found for C27H52BN3O6 m/z [548.7 (M+Na+), 526.7 (M+1), 570.8 (M+HCOO−), 524.6 (M−1)]. the solution was stirred an additional 16 h the solution was washed successively with water dried over MgSO4 filtered concentrated Purification by column chromatography (3% methanol in dichloromethane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under an atmosphere of argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I) dichloride (54 mg, 3% mol), diphenylphosphinoethane (64 mg, 6% mol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 mL, 10.7 mmol) in dry dichloromethane (20 mL) was cooled to 0° C. A second solution of tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)oct-7-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.5 g, 2.67 mmol) in dry dichloromethane (20 mL) was added in one portion. After 4 h LCMS indicated all the starting olefin was consumed and the reaction was washed successively with water, sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash chromatography (20-35% ethyl acetate in hexanes) gave tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a yellow oil (1.5 g, 93%). ESI MS found for C34H56BN3O6 m/z [614.7 (M+1), 633.7 (M+23)]. all the starting olefin was consumed the reaction was washed successively with water dried over MgSO4 filtered concentrated Purification by flash chromatography (20-35% ethyl acetate in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under an atmosphere of argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I) dichloride (54 mg, 3% mol), diphenylphosphinoethane (64 mg, 6% mol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 mL, 10.7 mmol) in dry dichloromethane (20 mL) was cooled to 0° C. A second solution of tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)oct-7-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.5 g, 2.67 mmol) in dry dichloromethane (20 mL) was added in one portion. After 4 h LCMS indicated all the starting olefin was consumed and the reaction was washed successively with water, sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash chromatography (20-35% ethyl acetate in hexanes) gave tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a yellow oil (1.5 g, 93%). ESI MS found for C34H56BN3O6 m/z [614.7 (M+1), 633.7 (M+23)]. all the starting olefin was consumed the reaction was washed successively with water dried over MgSO4 filtered concentrated Purification by flash chromatography (20-35% ethyl acetate in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I)dichloride (58 mg, 0.086 mmol) and diphenylphosphinoethane (68 mg, 0.172 mmol) in dichloromethane (10 mL) was cooled to 0° C., and charged with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.66 mL, 11.44 mmol). After stirring for 15 min, a solution of N-(3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide (1.46 g, −2.8 mmol) in dichloromethane (35 mL) was added in one portion and the resulting solution was allowed to slowly warm to room temperature. After stirring for 16 h dichloromethane (40 mL) added and the organic layer was washed with water and saturated aqueous sodium chloride. The resulting solution was dried over MgSO4, filtered and concentrated to give the crude product as a mixture of diastereomers. Purification by flash column chromatography (20-80% ethyl acetate in heptane) gave two products. The more lipophilic isomer was isolated and used in the next step (590 mg, 0.924 mmol). 1H NMR (CDCl3, 600 MHz) δ 8.65 (s, 1H), 7.97 (s, 1H), 7.67 (d, J=7.2 Hz, 2H), 7.49-7.53 (m, 3H), 7.40-7.43 (m, 4H), 6.17 (s, 1H), 3.37-3.42 (m, 1H), 3.30-3.34 (m, 1H), 2.72-2.80 (m, 2H), 2.39-2.51 (m, 2H), 2.31 (s, 3), 1.66-1.72 (m, 2H), 1.30 (s, 9H), 1.19 (s, 12H), 1.10-1.17 (m, 2H), 0.83-8.89 (m, 1H), 0.72 (t, J=7.8 Hz, 2H). ESI MS found for C35H49BClN3O5 m/z [638.7/640.8 (M+1), 636.7/638.9 (M−1)] added the organic layer was washed with water and saturated aqueous sodium chloride The resulting solution was dried over MgSO4 filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under argon, bis(1,5-dicyclooctadiene)diiridium(I)dichloride (15 mg, 0.022 mmol) and diphenylphosphinoethan (18 mg, 0.044 mmol) in dichloromethane (3 mL) was cooled to 0° C. and treated with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.430 mL, 2.95 mmol). After 30 min, a solution of 2-acetamido-N-tert-butyl-2-(3-(4-chlorobenzyl)-3-formamidocyclobutyl)hex-5-enamide (330 mg, 0.738 mmol) in dichloromethane (10 mL) was added and the cooling bath was removed. After 16 h, the solution was diluted with dichloromethane (20 mL) and washed with water and saturated aqueous sodium chloride. The organic layer was dried over MgSO4, filtered and concentrated to give the crude product (420 mg, 99%), which was used in the next step without further purification. ESI MS found for C30H47BClN3O5 m/z [576.8 (M+1), 574.7 (M−1)]. the cooling bath was removed After 16 h the solution was diluted with dichloromethane (20 mL) washed with water and saturated aqueous sodium chloride The organic layer was dried over MgSO4 filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under an atmosphere of argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I)dichloride (6 mg; 0.009 mmol) and diphenylphosphinoethane (7 mg, 0.018 mmol) in dichloromethane (1 mL) was cooled to 0° C. and treated with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.174 mL, 1.2 mmol). After stirring for 30 min, a solution of tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)oct-7-enylcarbamate (120 mg, 0.3 mmol) in dichloromethane (4 mL) was added and the solution was stirred an additional 16 h. Dichloromethane (10 mL) was added, and the solution was washed successively with water and sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by column chromatography (3% methanol in dichloromethane) gave tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)octylcarbamate (142 mg, 90%). ESI MS found for C27H52BN3O6 m/z [548.7 (M+Na+), 526.7 (M+1), 570.8 (M+HCOO−), 524.6 (M−1)]. the solution was stirred an additional 16 h the solution was washed successively with water dried over MgSO4 filtered concentrated Purification by column chromatography (3% methanol in dichloromethane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While under an atmosphere of argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I) dichloride (54 mg, 3% mol), diphenylphosphinoethane (64 mg, 6% mol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 mL, 10.7 mmol) in dry dichloromethane (20 mL) was cooled to 0° C. A second solution of tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)oct-7-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.5 g, 2.67 mmol) in dry dichloromethane (20 mL) was added in one portion. After 4 h LCMS indicated all the starting olefin was consumed and the reaction was washed successively with water, sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash chromatography (20-35% ethyl acetate in hexanes) gave tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a yellow oil (1.5 g, 93%). ESI MS found for C34H56BN3O6 m/z [614.7 (M+1), 633.7 (M+23)]. all the starting olefin was consumed the reaction was washed successively with water dried over MgSO4 filtered concentrated Purification by flash chromatography (20-35% ethyl acetate in hexanes)