N-Allylaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: N-allylaniline (0.200 mole) and 1,1,3,3-tetramethyldisiloxane (0.100 mole) are introduced along with 0.05 g hexachloroplatinic acid into a 100 ml cylindrical glass reactor equipped with reflux condenser, nitrogen inlet, and stir bar. The contents of the reaction are heated and maintained while stirring, at approximately 70° C., for a period of ten hours. The IR spectrum of the resulting viscous oil shows no peaks corresponding to Si-H, indicating completion of the reaction. The crude product is mixed with carbon black and stirred overnight at room temperature. The product is filtered through silica gel and the filter cake washed with toluene. Volatile fractions are removed by stripping under vacuum at 150° C. to give a slightly colored oil. The oil is further purified by vacuum distillation at <1 torr at 223°-230° C. The yield of 1,3-bis(N-phenyl-3-aminopropyl)-1,1,3,3-tetramethyldisiloxane is virtually quantitative. equipped with reflux condenser, nitrogen inlet The contents of the reaction are heated maintained while stirring, at approximately 70° C., for a period of ten hours completion of the reaction stirred overnight at room temperature The product is filtered through silica gel the filter cake washed with toluene Volatile fractions are removed by stripping under vacuum at 150° C. to give a slightly colored oil The oil is further purified by vacuum distillation at <1 torr at 223°-230° C

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

Procedure: N-allylaniline (0.200 mole) and 1,1,3,3-tetramethyldisiloxane (0.100 mole) are introduced along with 0.05 g hexachloroplatinic acid into a 100 ml cylindrical glass reactor equipped with reflux condenser, nitrogen inlet, and stir bar. The contents of the reaction are heated and maintained while stirring, at approximately 70° C., for a period of ten hours. The IR spectrum of the resulting viscous oil shows no peaks corresponding to Si-H, indicating completion of the reaction. The crude product is mixed with carbon black and stirred overnight at room temperature. The product is filtered through silica gel and the filter cake washed with toluene. Volatile fractions are removed by stripping under vacuum at 150° C. to give a slightly colored oil. The oil is further purified by vacuum distillation at <1 torr at 223°-230° C. The yield of 1,3-bis(N-phenyl-3-aminopropyl)-1,1,3,3-tetramethyldisiloxane is virtually quantitative. equipped with reflux condenser, nitrogen inlet The contents of the reaction are heated maintained while stirring, at approximately 70° C., for a period of ten hours completion of the reaction stirred overnight at room temperature The product is filtered through silica gel the filter cake washed with toluene Volatile fractions are removed by stripping under vacuum at 150° C. to give a slightly colored oil The oil is further purified by vacuum distillation at <1 torr at 223°-230° C

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

Procedure: Following the general procedure, N-allylaniline (50.0 mg, 0.375 mmol) was treated with butyl vinyl ether (376 mg, 3.75 mmol) and 5 mol % of in situ-generated complex 1a (188 μL, 0.10 M, 18.7 μmol; final substrate concentration=2.0 M) and allowed to stir for 4 h. The unpurified product is 96% Z (as determined by 400 MHz 1H NMR analysis). The resulting oil was purified by silica gel chromatography (50:1 hexanes:Et2O) to afford 8e (40.2 mg, 0.196 mmol , 52.0% yield, 96% Z isomer) as a light yellow oil. IR (neat): 3410 (br), 3048 (w), 2958 (m), 2932 (m), 2871 (m), 1660 (m), 1601 (s), 1503 (s), 1467 (m), 1431(w), 1375 (m), 1314 (m), 1250 (m), 1108 (s), 1094 (s), 1040 (m), 745 (s), 691 (s); 1H NMR (400 MHz, CDCl3): ™ δ 7.19-7.14 (2H, m), 6.72-6.67 (1H, m), 6.66-6.62 (2H, m), [diagnostic E isomer signal: 6.51 (1H, d, J=12.8 Hz)], 6.08 (1H, dt, J=6.4, 1.4 Hz), 4.51 (1H, td, J=6.6, 6.4 Hz), 3.82-3.74 (1H, m), 3.81 (2H, dd, J=6.8, 1.2 Hz), 3.79 (2H, t, J=6.4 Hz), 1.67-1.59 (2H, m), 1.47-1.37 (2H, m), 0.95 (3H, t, J=7.4 Hz); 13C NMR (100 MHz, CDCl3): ™ δ 148.5, 147.4, 129.3, 117.4, 113.2, 103.5, 72.6, 38.6, 32.0, 19.2, 14.0; HRMS (ESI+) [M+H]+ calcd for C13H20NO: 206.1545, found: 206.1541. The resulting oil was purified by silica gel chromatography (50:1 hexanes:Et2O)

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

Procedure: N-Allylaniline [NMR (200 MHz, DMSO-d6): δ3.68 (t, J=5.2 Hz, 2H); 5.10 (d, J=10.2 Hz, 1H); 5.23 (d, J=17.2 Hz, 1H); 5.78 (br s, 1H); 5.75-5.97 (m, 1H); 6.52 (t, J=7.3 Hz, 2H); 6.56 (d, J=7.8 Hz, 2H); 7.06 (t, J=7.3 Hz, 2H)] was prepared from aniline and allyl bromide via trifluoroacetanilide using the general method described by Hodge (Harland, P.A.; Hodge, P; Maughan, W.; Wildsmith, E. Synthesis, 1984, 941). described by Hodge (Harland, P.A.; Hodge, P; Maughan, W.; Wildsmith, E. Synthesis, 1984, 941)

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

Procedure: A solution of N-propylphosphonic acid anhydride cyclic trimer (50% reagent in EtOAc solution, 1.26 mL, 2.14 mmol) was added to a degassed solution of (S)-2-(tert-butoxycarbonylamino)pent-4-enoic acid (230 mg, 1.07 mmol), N-allylaniline (142 mg, 1.07 mmol), and Hunig's Base (0.560 mL, 3.21 mmol) at 0° C. The reaction mixture was stirred under argon for 2 min at 0° C. and then warmed to rt and stirred for 1 hr. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-30% EtOAc/Hex to give (S)-tert-butyl 1-(allyl(phenyl)amino)-1-oxopent-4-en-2-ylcarbamate (195 mg, 0.590 mmol, 55.2% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.43 (t, J=7.4 Hz, 2H), 7.36 (t, J=7.3 Hz, 1H), 7.24 (d, J=7.5 Hz, 2H), 5.91-5.78 (m, 1H), 5.63-5.49 (m, 1H), 5.23 (d, J=8.4 Hz, 1H), 5.18-5.05 (m, 2H), 5.05-4.94 (m, 2H), 4.43-4.19 (m, 3H), 2.33-2.23 (m, 1H), 2.20-2.08 (m, 1H), 1.45 (s, 9H). warmed to rt stirred for 1 hr washed with saturated aqueous NaHCO3 and saturated aqueous NaCl dried over Na2SO4 filtered concentrated The crude product was purified eluting with a gradient of 0-30% EtOAc/Hex

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

Procedure: A solution of N-propylphosphonic acid anhydride cyclic trimer (50% reagent in EtOAc solution, 1.26 mL, 2.14 mmol) was added to a degassed solution of (S)-2-(tert-butoxycarbonylamino)pent-4-enoic acid (230 mg, 1.07 mmol), N-allylaniline (142 mg, 1.07 mmol), and Hunig's Base (0.560 mL, 3.21 mmol) at 0° C. The reaction mixture was stirred under argon for 2 min at 0° C. and then warmed to rt and stirred for 1 hr. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-30% EtOAc/Hex to give (S)-tert-butyl 1-(allyl(phenyl)amino)-1-oxopent-4-en-2-ylcarbamate (195 mg, 0.590 mmol, 55.2% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.43 (t, J=7.4 Hz, 2H), 7.36 (t, J=7.3 Hz, 1H), 7.24 (d, J=7.5 Hz, 2H), 5.91-5.78 (m, 1H), 5.63-5.49 (m, 1H), 5.23 (d, J=8.4 Hz, 1H), 5.18-5.05 (m, 2H), 5.05-4.94 (m, 2H), 4.43-4.19 (m, 3H), 2.33-2.23 (m, 1H), 2.20-2.08 (m, 1H), 1.45 (s, 9H). warmed to rt stirred for 1 hr washed with saturated aqueous NaHCO3 and saturated aqueous NaCl dried over Na2SO4 filtered concentrated The crude product was purified eluting with a gradient of 0-30% EtOAc/Hex

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

Procedure: To a round bottom flask was added 2-(tert-butoxycarbonylamino)-3,3-dimethylpent-4-enoic acid (120 mg, 0.493 mmol), N-allylaniline (0.134 mL, 0.986 mmol), EtOAc (5 mL) and Hunig's Base (0.258 mL, 1.48 mmol). The reaction mixture was cooled to 0° C. 1-propanephosphonic acid cyclic anhydride (314 mg, 0.986 mmol) was added and the reaction was stirred at 0° C. for 5 min and then at rt for 3 days. The reaction mixture was diluted with EtOAc (20 mL) and washed with water (10 mL) and saturated aqueous NaCl (10 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC (Method A) to give tert-butyl 1-(allyl(phenyl)amino)-3,3-dimethyl-1-oxopent-4-en-2-ylcarbamate (70 mg, 0.20 mmol, 40% yield) as clear oil. Anal. Calcd. for C21H30N2O3 m/z 358.2. found: 359.2 (M+H)+. at rt for 3 days washed with water (10 mL) and saturated aqueous NaCl (10 mL) The organic layer was separated dried over MgSO4 filtered concentrated The residue was purified by RP prep-HPLC (Method A)