(E)-3-(2-methoxyphenyl)prop-2-enal

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

Procedure: [Ir(cod)Cl]2, O,O′-(R)-(1,1′-Dinaphthyl-2,2′-diyl)-N,N′-di-(R,R)-phenylethylphosphoramidite were prepared according to published procedures (Herde, J. L.; Lambert, J. C.; Senoff, C. V. Inorg. Synth. 1974, 15, 18; Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim, C. Synlett 2001, 1375). Lithium aryloxides were prepared by reaction of the corresponding phenols with n-BuLi in THF at 0° C. After being stirred for 10 min at room temperature, the solution was concentrated under vacuum to afford the corresponding lithium aryloxides as white powders, which were stored under inert atmosphere. All allylic carbonates were synthesized by the reaction of the corresponding allylic alcohols with the corresponding alkylchloroformate in the presence of pyridine. (E)-4-Methoxycinnamamyl alcohol and (E)-2-methoxycinnamyl alcohol were prepared by the reduction of the corresponding aldehydes with DIBAL-H (Nung Min, Y.; Young Soo, G. J. Org. Chem. 1985, 50, 2443). Phenols, (E)-4-methoxycinnamaldehyde, and (E)-2-methoxycinnamaldehyde were purchased from Aldrich Chemicals Co. and used without further purification. and used without further purification

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

Procedure: [Ir(cod)Cl]2, O,O′-(R)-(1,1′-Dinaphthyl-2,2′-diyl)-N,N′-di-(R,R)-phenylethylphosphoramidite were prepared according to published procedures (Herde, J. L.; Lambert, J. C.; Senoff, C. V. Inorg. Synth. 1974, 15, 18; Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim, C. Synlett 2001, 1375). Lithium aryloxides were prepared by reaction of the corresponding phenols with n-BuLi in THF at 0° C. After being stirred for 10 min at room temperature, the solution was concentrated under vacuum to afford the corresponding lithium aryloxides as white powders, which were stored under inert atmosphere. All allylic carbonates were synthesized by the reaction of the corresponding allylic alcohols with the corresponding alkylchloroformate in the presence of pyridine. (E)-4-Methoxycinnamamyl alcohol and (E)-2-methoxycinnamyl alcohol were prepared by the reduction of the corresponding aldehydes with DIBAL-H (Nung Min, Y.; Young Soo, G. J. Org. Chem. 1985, 50, 2443). Phenols, (E)-4-methoxycinnamaldehyde, and (E)-2-methoxycinnamaldehyde were purchased from Aldrich Chemicals Co. and used without further purification. and used without further purification

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28%-Sodium metholate-methanol solution (4.4 ml) was diluted with methanol (5 ml), and cooled to −20° C. A solution of (2E)-3-(2-methoxyphenyl)prop-2-enal (2.4 g) and ethyl azidoacetate (7.5 g) in methanol (8 ml) was added over 30 min, and the mixture was stirred at −10° C. for 1 hr and at room temperature for 2 hr. The reaction mixture was poured into water and extracted with ether. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give methyl (2Z,4E)-2-azido-5-(2-methoxyphenyl)penta-2,4-dienoate (3.6 g). A part (3.5 g) thereof was dissolved in chloroform (10 ml), zinc iodide (214 mg) was added and the mixture was stirred at room temperature for 12 hr. The reaction mixture was poured into water, and extracted with 1,2-dichloroethane. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give the object product (3.26 g). extracted with ether The extract was washed with brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28%-Sodium metholate-methanol solution (4.4 ml) was diluted with methanol (5 ml), and cooled to −20° C. A solution of (2E)-3-(2-methoxyphenyl)prop-2-enal (2.4 g) and ethyl azidoacetate (7.5 g) in methanol (8 ml) was added over 30 min, and the mixture was stirred at −10° C. for 1 hr and at room temperature for 2 hr. The reaction mixture was poured into water and extracted with ether. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give methyl (2Z,4E)-2-azido-5-(2-methoxyphenyl)penta-2,4-dienoate (3.6 g). A part (3.5 g) thereof was dissolved in chloroform (10 ml), zinc iodide (214 mg) was added and the mixture was stirred at room temperature for 12 hr. The reaction mixture was poured into water, and extracted with 1,2-dichloroethane. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give the object product (3.26 g). extracted with ether The extract was washed with brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure

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

Procedure: Prepared according to the general procedure using (Z)-4-benzylidene-2-(2,5-difluorophenyl)-1H-imidazol-5(4H)-one and (E)-3-(2-methoxyphenyl)acrylaldehyde. The unpurified residue was purified by flash chromatography using 15% EtOAc/hexanes to afford 10 as an off-white solid (81 mg, 61%). Analytical data for 10: 1H NMR (500 MHz, CDCl3) δ 9.34 (d, J=8.1 Hz, 1H), 7.89 (ddd, J=9.2, 6.0, 3.2 Hz, 1H), 7.38-7.29 (m, 3H), 7.27-7.21 (m, 1H), 7.09-7.00 (m, 3H), 7.00-6.92 (m, 1H), 6.91 (dd, J=7.6, 1.8 Hz, 1H), 6.86 (ap t, J=7.5 Hz, 2H), 4.06 (d, J=6.9 Hz, 1H), 3.84 (ddd, J=8.9, 6.9, 5.2 Hz, 1H), 3.80 (s, 3H), 3.26 (dd, J=14.2, 5.2 Hz, 1H), 2.49 (dd, J=14.2, 8.8 Hz, 1H); 13C NMR (CDCl3, 126 MHz) δ 169.4, 159.1 (d, JCF=243.7 Hz), 157.8, 155.3 (d, JCF=240.5 Hz), 148.9, 137.6, 136.1, 131.9, 129.1, 128.1, 128.0, 126.0, 120.2, 117.1 (dd, JCF=25.8, 8.7 Hz), 116.4 (dd, JCF=24.7, 9.4 Hz), 114.5 (dd, JCF=27.5, 3.0 Hz), 111.3 (d, JCF=2.9 Hz), 110.1, 55.2, 44.8, 39.0, 29.1; IR (film) cm−1 1773, 1637, 1482, 1464, 1243, 1173, 1122, 1101, 1030, 813, 765, 738, 700; LRMS (ESI): Mass calcd for [M+H]+ C26H21F2N2O3: 447.1. found 447.4; Enantiomeric ratio was measured by chiral phase HPLC (Chiralcel OD-H; 5% IPA/3% MeOH/hexanes 0.5 mL/min, 280 nm), Rt1 (minor)=32.2, Rt2 (major)=42.5 min; er=96:4. Prepared The unpurified residue was purified by flash chromatography

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28%-Sodium metholate-methanol solution (4.4 ml) was diluted with methanol (5 ml), and cooled to −20° C. A solution of (2E)-3-(2-methoxyphenyl)prop-2-enal (2.4 g) and ethyl azidoacetate (7.5 g) in methanol (8 ml) was added over 30 min, and the mixture was stirred at −10° C. for 1 hr and at room temperature for 2 hr. The reaction mixture was poured into water and extracted with ether. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give methyl(2Z,4E)-2-azido-5-(2-methoxyphenyl)penta-2,4-dienoate (3.6 g). A part (3.5 g) thereof was dissolved in chloroform (10 ml), zinc iodide (214 mg) was added and the mixture was stirred at room temperature for 12 hr. The reaction mixture was poured into water, and extracted with 1,2-dichloroethane. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give the object product (3.26 g). extracted with ether The extract was washed with brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28%-Sodium metholate-methanol solution (4.4 ml) was diluted with methanol (5 ml), and cooled to −20° C. A solution of (2E)-3-(2-methoxyphenyl)prop-2-enal (2.4 g) and ethyl azidoacetate (7.5 g) in methanol (8 ml) was added over 30 min, and the mixture was stirred at −10° C. for 1 hr and at room temperature for 2 hr. The reaction mixture was poured into water and extracted with ether. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give methyl(2Z,4E)-2-azido-5-(2-methoxyphenyl)penta-2,4-dienoate (3.6 g). A part (3.5 g) thereof was dissolved in chloroform (10 ml), zinc iodide (214 mg) was added and the mixture was stirred at room temperature for 12 hr. The reaction mixture was poured into water, and extracted with 1,2-dichloroethane. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure to give the object product (3.26 g). extracted with ether The extract was washed with brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure a fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure

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

Procedure: [Ir(cod)Cl]2, O,O′-(R)-(1,1′-Dinaphthyl-2,2′-diyl)-N,N′-di-(R,R)-phenylethylphosphoramidite were prepared according to published procedures (Herde, J. L.; Lambert, J. C.; Senoff, C. V. Inorg. Synth. 1974, 15, 18; Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim, C. Synlett 2001, 1375). Lithium aryloxides were prepared by reaction of the corresponding phenols with n-BuLi in THF at 0° C. After being stirred for 10 min at room temperature, the solution was concentrated under vacuum to afford the corresponding lithium aryloxides as white powders, which were stored under inert atmosphere. All allylic carbonates were synthesized by the reaction of the corresponding allylic alcohols with the corresponding alkylchloroformate in the presence of pyridine. (E)-4-Methoxycinnamamyl alcohol and (E)-2-methoxycinnamyl alcohol were prepared by the reduction of the corresponding aldehydes with DIBAL-H (Nung Min, Y.; Young Soo, G. J. Org. Chem. 1985, 50, 2443). Phenols, (E)-4-methoxycinnamaldehyde, and (E)-2-methoxycinnamaldehyde were purchased from Aldrich Chemicals Co. and used without further purification. and used without further purification