2-vinylbenzaldehyde

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

Procedure: To the Compound 2a (106 mmol) in anhydrous methanol (100 ml) was added methyl 3-aminocrotonate (106 mmol) and methyl acetoacetate (106 mmol) and the resulting solution heated at reflux under nitrogen for 4 days. The solvent was removed in vacuo to give a viscous yellow oil which was diluted in diethyl ether (75 ml) and then hexane (50 ml). After stirring overnight, a yellow solid was collected by filtration and purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2) to give Compound 2b as a yellow solid (Rf =0.4, m.p. 140°-148°). the resulting solution heated at reflux under nitrogen for 4 days The solvent was removed in vacuo to give a viscous yellow oil which a yellow solid was collected by filtration purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2)

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

Procedure: To the Compound 2a (106 mmol) in anhydrous methanol (100 ml) was added methyl 3-aminocrotonate (106 mmol) and methyl acetoacetate (106 mmol) and the resulting solution heated at reflux under nitrogen for 4 days. The solvent was removed in vacuo to give a viscous yellow oil which was diluted in diethyl ether (75 ml) and then hexane (50 ml). After stirring overnight, a yellow solid was collected by filtration and purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2) to give Compound 2b as a yellow solid (Rf =0.4, m.p. 140°-148°). the resulting solution heated at reflux under nitrogen for 4 days The solvent was removed in vacuo to give a viscous yellow oil which a yellow solid was collected by filtration purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromostyrene (115 mmol) in dry tetrahydrofuran (200 ml) at -65° C. under nitrogen was added dropwise n-butyllithium (115 mmol) in hexane. The reaction mixture was stirred at -65° C. for an additional hour and a solution of N-formylpiperidine (125 mmol) in tetrahydrofuran (50 ml) was added dropwise. The reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was cooled to 0° C. and then quenched with saturated ammonium chloride (50 ml). The reaction mixture was extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield the Compound 2a which was directly used in the next reaction. to warm to ambient temperature overnight The reaction mixture was cooled to 0° C. quenched with saturated ammonium chloride (50 ml) The reaction mixture was extracted with diethyl ether (2×50 ml) the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated in vacuo

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromostyrene (115 mmol) in dry tetrahydrofuran (200 ml) at -65° C. under nitrogen was added dropwise n-butyllithium (115 mmol) in hexane. The reaction mixture was stirred at -65° C. for an additional hour and a solution of N-formylpiperidine (125 mmol) in tetrahydrofuran (50 ml) was added dropwise. The reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was cooled to 0° C. and then quenched with saturated ammonium chloride (50 ml). The reaction mixture was extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield the Compound 2a which was directly used in the next reaction. to warm to ambient temperature overnight The reaction mixture was cooled to 0° C. quenched with saturated ammonium chloride (50 ml) The reaction mixture was extracted with diethyl ether (2×50 ml) the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated in vacuo

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

Procedure: To the Compound 2a (106 mmol) in anhydrous methanol (100 ml) was added methyl 3-aminocrotonate (106 mmol) and methyl acetoacetate (106 mmol) and the resulting solution heated at reflux under nitrogen for 4 days. The solvent was removed in vacuo to give a viscous yellow oil which was diluted in diethyl ether (75 ml) and then hexane (50 ml). After stirring overnight, a yellow solid was collected by filtration and purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2) to give Compound 2b as a yellow solid (Rf =0.4, m.p. 140°-148°). the resulting solution heated at reflux under nitrogen for 4 days The solvent was removed in vacuo to give a viscous yellow oil which a yellow solid was collected by filtration purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromostyrene (115 mmol) in dry tetrahydrofuran (200 ml) at -65° C. under nitrogen was added dropwise n-butyllithium (115 mmol) in hexane. The reaction mixture was stirred at -65° C. for an additional hour and a solution of N-formylpiperidine (125 mmol) in tetrahydrofuran (50 ml) was added dropwise. The reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was cooled to 0° C. and then quenched with saturated ammonium chloride (50 ml). The reaction mixture was extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield the Compound 2a which was directly used in the next reaction. to warm to ambient temperature overnight The reaction mixture was cooled to 0° C. quenched with saturated ammonium chloride (50 ml) The reaction mixture was extracted with diethyl ether (2×50 ml) the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated in vacuo

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

Procedure: Aldehyde 11 was synthesized by radical addition (Lub et al. (1997) Liebigs Ann. Recueil, 2281-2288) of thioacetic acid to 4-vinylbenzaldehyde. Vinyl benzaldehyde was synthesized by the procedure of Ren et al. (1993) Bull. Chem. Soc. Jpn. 66: 1897-1902 with the following changes: The addition of DMF was performed at a 38 mmol scale at 0° C. Purification by column chromatography (silica, Et2O/hexanes, 1:3) afforded 4-vinylbenzaldehyde in 60% yield (FIG. 37)/ was performed at a 38 mmol scale at 0° C Purification by column chromatography (silica, Et2O/hexanes, 1:3)

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

Procedure: Aldehyde 11 was synthesized by radical addition (Lub et al. (1997) Liebigs Ann. Recueil, 2281–2288) of thioacetic acid to 4-vinylbenzaldehyde. Vinyl benzaldehyde was synthesized by the procedure of Ren et al. (1993) Bull. Chem. Soc. Jpn. 66: 1897–1902 with the following changes: The addition of DMF was performed at a 38 mmol scale at 0° C. Purification by column chromatography (silica, Et2O/hexanes, 1:3) afforded 4-vinylbenzaldehyde in 60% yield (FIG. 37). was performed at a 38 mmol scale at 0° C Purification by column chromatography (silica, Et2O/hexanes, 1:3)

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

Procedure: A mixture of 2-vinylbenzaldehyde (2.9 g, 22 mmol) and trimethylsilyl chloride (11 ml) in ethylene glycol (95 ml) was stirred for 16 h, diluted with saturated sodium bicarbonate solution, extracted with ether, dried over sodium sulphate and evaporated to afford a colourless oil (2.7 g), MS (+EI) 176 (M+), 1H NMR (CDCl3) 7.57 (1H, m), 7.53 (1H, dd, J1.5, 7.5 Hz), 7.36-7.30 (2H, m), 7.14 (1H, dd, J11, 17.4 Hz), 6.04 (1H, s) 5.69 (1H, dd, J1.3, 17.4 Hz), 5.34 (1H, dd, J1.3, 11.0 Hz), 4.18-4.04 (2H, m), 3.77-3.65 (2H, m). extracted with ether dried over sodium sulphate evaporated

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

Procedure: To the Compound 2a (106 mmol) in anhydrous methanol (100 ml) was added methyl 3-aminocrotonate (106 mmol) and methyl acetoacetate (106 mmol) and the resulting solution heated at reflux under nitrogen for 4 days. The solvent was removed in vacuo to give a viscous yellow oil which was diluted in diethyl ether (75 ml) and then hexane (50 ml). After stirring overnight, a yellow solid was collected by filtration and purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2) to give Compound 2b as a yellow solid (Rf =0.4, m.p. 140°-148°). the resulting solution heated at reflux under nitrogen for 4 days The solvent was removed in vacuo to give a viscous yellow oil which a yellow solid was collected by filtration purified by flash chromatography on silica gel eluted with hexane:diethyl ether (1:2)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromostyrene (115 mmol) in dry tetrahydrofuran (200 ml) at -65° C. under nitrogen was added dropwise n-butyllithium (115 mmol) in hexane. The reaction mixture was stirred at -65° C. for an additional hour and a solution of N-formylpiperidine (125 mmol) in tetrahydrofuran (50 ml) was added dropwise. The reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was cooled to 0° C. and then quenched with saturated ammonium chloride (50 ml). The reaction mixture was extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield the Compound 2a which was directly used in the next reaction. to warm to ambient temperature overnight The reaction mixture was cooled to 0° C. quenched with saturated ammonium chloride (50 ml) The reaction mixture was extracted with diethyl ether (2×50 ml) the combined organic phases were washed with 3N hydrochloric acid (2×50 ml), saturated aqueous sodium bicarbonate (50 ml), and brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated in vacuo