ethyl (E)-4-oxobut-2-enoate

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-5-cyanopyridine (5.0 g, 39.9 mmol) and ethyl-(E)-4-oxobutenoate (5.92 g, 43.9 mmol, 1.1 equiv) are dissolved in acetonitrile (25 ml). The solution is heated for 14 hours at 90° C. After cooling, volatiles are removed in vacuo, and the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50) to afford the title compound (2.77 g, 29%). 1H NMR (400 MHz, d6-DMSO): δ=9.17-9.15 (m, 1H), 7.60 (dd, J=9.3/1.0 Hz, 1H), 7.54 (s, 1H), 7.37 (dd, J=9.3/1.7 Hz, 1H), 4.07 (s, 2H), 3.99 (q, J=7.4 Hz, 2H), 1.07 (t, J=7.1 Hz, 3H). MS (ES+): 230 (M+H)+. After cooling volatiles are removed in vacuo the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50)

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

Procedure: DBU (7.5 mg, 0.05 mmol) was added under argon to a solution of (E)-ethyl 3-formylacrylate (128 mg, 1 mmol), nitrosobenzene (107 mg, 1 mmol) and catalyst (18.2 mg, 0.05 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 10 min. The solvent was removed under vacuum, and the residue was purified by flash silica gel column chromatography using hexane and ethyl acetate as the eluents. The solvent was removed under vacuum the residue was purified by flash silica gel column chromatography

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-5-cyanopyridine (5.0 g, 39.9 mmol) and ethyl-(E)-4-oxobutenoate (5.92 g, 43.9 mmol, 1.1 equiv) are dissolved in acetonitrile (25 ml). The solution is heated for 14 hours at 90° C. After cooling, volatiles are removed in vacuo, and the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50) to afford the title compound (2.77 g, 29%). 1H NMR (400 MHz, d6-DMSO): δ=9.17-9.15 (m, 1H), 7.60 (dd, J=9.3/1.0 Hz, 1H), 7.54 (s, 1H), 7.37 (dd, J=9.3/1.7 Hz, 1H), 4.07 (s, 2H), 3.99 (q, J=7.4 Hz, 2H), 1.07 (t, J=7.1 Hz, 3H). MS (ES+): 230 (M+H)+. After cooling volatiles are removed in vacuo the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-5-cyanopyridine (5.0 g, 39.9 mmol) and ethyl-(E)-4-oxobutenoate (5.92 g, 43.9 mmol, 1.1 equiv) are dissolved in acetonitrile (25 ml). The solution is heated for 14 hours at 90° C. After cooling, volatiles are removed in vacuo, and the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50) to afford the title compound (2.77 g, 29%). 1H NMR (400 MHz, d6-DMSO): δ=9.17-9.15 (m, 1H), 7.60 (dd, J=9.3/1.0 Hz, 1H), 7.54 (s, 1H), 7.37 (dd, J=9.3/1.7 Hz, 1H), 4.07 (s, 2H), 3.99 (q, J=7.4 Hz, 2H), 1.07 (t, J=7.1 Hz, 3H). MS (ES+): 230 (M+H)+. After cooling volatiles are removed in vacuo the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Amino-5-cyanopyridine (5.0 g, 39.9 mmol) and ethyl-(E)-4-oxobutenoate (5.92 g, 43.9 mmol, 1.1 equiv) are dissolved in acetonitrile (25 ml). The solution is heated for 14 hours at 90° C. After cooling, volatiles are removed in vacuo, and the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50) to afford the title compound (2.77 g, 29%). 1H NMR (400 MHz, d6-DMSO): δ=9.17-9.15 (m, 1H), 7.60 (dd, J=9.3/1.0 Hz, 1H), 7.54 (s, 1H), 7.37 (dd, J=9.3/1.7 Hz, 1H), 4.07 (s, 2H), 3.99 (q, J=7.4 Hz, 2H), 1.07 (t, J=7.1 Hz, 3H). MS (ES+): 230 (M+H)+. After cooling volatiles are removed in vacuo the residue is purified by flash chromatography (gradient hexane/EtOAc 100:0 to 50:50)

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

Procedure: To a stirred mixture of commercially available (S)-(−)-α{tilde over (α)}Diphenyl-2-pyrrolidinemethanol (0.83 g, 3.28 mmol) in toluene (40 mL) was added 2-nitrobenzoic acid (0.55 g, 3.28 mmol), commercially available 2-Hydroxybenzaldehyde (2.00 g, 16.38 mmol) and (E)-4-oxo-but-2-enoic acid ethyl ester (2.51 g, 19.65 mmol). After addition was complete the mixture was stirred at room temperature for 3 days. Upon completion of the reaction the toluene was removed by vacuum distillation. The residue was diluted with ethyl acetate and washed with water, a saturated sodium bicarbonate solution and a saturated sodium chloride solution. The organic fraction was then dried over magnesium sulfate. The crude product obtained was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; (0% to 100% ethyl acetate/hexane) to afford 3-formyl-2H-chromene-2-carboxylic acid ethyl ester as a yellow oil, 1.09 g (29% yield). (Ref: Chem. Eur. Journal; 2007, 13, pg 574). After addition was removed by vacuum distillation The residue was diluted with ethyl acetate washed with water The organic fraction was then dried over magnesium sulfate The crude product obtained was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-Oxo-but-2-enoic acid ethyl ester (2.7 mL, 22.99 mmol), 2-nitro benzoic acid (0.648 g, 3.83 mmol), and pyrrolidine (0.31 mL, 3.83 mmol) were added simultaneously to a solution of commercially available 3-chloro-2-hydroxy-benzaldehyde (5.0 g, 19.16 mmol) in dimethysulfoxide (20 mL) at 25° C. and the solution was stirred for 78 hours at 25° C. The reaction was quenched by the addition of water. The reaction mixture was then partitioned between water and ethyl acetate. The combined organics were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, rinsed and concentrated in vacuo. The residue obtained was purified on a silica gel Flash column chromatography using ethyl acetate-hexanes (1:1.2) as eluents, yielded 5-chloro-3-formyl-2H-chromene-2-carboxylic acid ethyl ester as a solid (2.10 g, 50.1%). The reaction was quenched by the addition of water The reaction mixture was then partitioned between water and ethyl acetate The combined organics were washed with a saturated brine solution dried over anhydrous sodium sulfate filtered rinsed concentrated in vacuo The residue obtained was purified on a silica gel Flash column chromatography

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-oxo-but-2-enoic acid ethyl ester (7.30 mL, 60.37 mmol), 2-nitro benzoic acid (1.852 g, 10.98 mmol), and pyrrolidine (0.91 mL, 10.98 mmol) were added simultaneously to a solution of commercially available 2-hydroxy-3,6-dimethoxy-benzaldehyde (10.0 g, 54.89 mmol) in dimethysulfoxide (50 mL) at 25° C. and the solution was stirred for 78 hours at 25° C. The reaction was quenched by the addition of water. The reaction mixture was then partitioned between water and ethyl acetate. The combined organics were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, rinsed and concentrated in vacuo. The residue obtained was purified on a silica gel flash column chromatography using ethyl acetate-hexanes (1:1.2) as eluents, yielding 3-formyl-5,8-dimethoxy-2H-chromene-2-carboxylic acid ethyl ester (3.5 g, 62.3%). The reaction was quenched by the addition of water The reaction mixture was then partitioned between water and ethyl acetate The combined organics were washed with a saturated brine solution dried over anhydrous sodium sulfate filtered rinsed concentrated in vacuo The residue obtained was purified on a silica gel flash column chromatography

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-oxo-but-2-enoic acid ethyl ester (7.63 mL, 63.09 mmol), 2-nitro benzoic acid (1.77 g, 10.52 mmol), and pyrrolidine (0.87 mL, 10.52 mmol) were added simultaneously to a solution of commercially available 2-hydroxy-6-methoxy-benzaldehyde (8.0 g, 52.58 mmol) in dimethysulfoxide (50 mL) at 25° C. and the solution was stirred for 78 hours at 25° C. The reaction was quenched by the addition of water. The reaction mixture was then partitioned between water and ethyl acetate. The combined organics were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, rinsed and concentrated in vacuo. The residue obtained was purified on a silica gel flash column chromatography using ethyl acetate-hexanes as eluants, yielding 5-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester as a solid (1.80 g, 51.9%). The reaction was quenched by the addition of water The reaction mixture was then partitioned between water and ethyl acetate The combined organics were washed with a saturated brine solution dried over anhydrous sodium sulfate filtered rinsed concentrated in vacuo The residue obtained was purified on a silica gel flash column chromatography

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-4-Oxo-but-2-enoic acid ethyl ester (4.60 mL, 38.32 mmol), 2-nitrobenzoic acid (1.08 g, 6.39 mmol), and pyrrolidine (0.53 mL, 6.39 mmol) were added simultaneously to a solution of commercially available 2-chloro-6-hydroxy-benzaldehyde (5.0 g, 31.93 mmol) in dimethysulfoxide (30 mL) at 25° C. and the solution was stirred for 78 hours at 25° C. The reaction was quenched by the addition of water. The reaction mixture was then partitioned between water and ethyl acetate. The combined organics were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, rinsed and concentrated in vacuo. The residue obtained was purified on a silica gel Flash column chromatography using ethyl acetate-hexanes (1:1.2) as eluents, yielding 5-chloro-3-formyl-2H-chromene-2-carboxylic acid ethyl ester as a solid (2.08 g, 49.5%). The reaction was quenched by the addition of water The reaction mixture was then partitioned between water and ethyl acetate The combined organics were washed with a saturated brine solution dried over anhydrous sodium sulfate filtered rinsed concentrated in vacuo The residue obtained was purified on a silica gel Flash column chromatography

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

Procedure: The title compound was prepared according to the general procedure from ethyl trans-4-oxo-2-butenoate and trans-N-(4-methoxybenzenesulfonyl)-3-(furan-2-yl)prop-2-en-1-imine using 10 mol % 9 as the catalyst in 71% yield as a yellow solid. [α]D20 (c 1.58, CHCl3)=+125.7; mp=98-100° C.; 1H NMR (400 MHz, CDCl3) δ 7.98 (dd, 2H, J=7.0, 1.9 Hz), 7.12 (d, 2H, J=8.0 Hz), 7.00 (dd, 21-1, J=7.0, 1.9 Hz), 6.87 (d, 1H, J=1.8 Hz), 6.11 (dd, 1H, J=3.2, 1.8 Hz), 5.82 (d, 1H, J=3.2 Hz), 5.51 (dd, 1H, J=8.0, 6.8 Hz), 4.15-4.10 (m, 2H), 3.90 (s, 3H), 3.75 (t, 1H, J=6.7 Hz), 3.45-3.40 (m, 1H), 2.72 (dd, 1H, J=17.3, 6.0 Hz), 2.52 (s, 3H), 2.04 (dd, 1H, J=17.3, 7.7 Hz), 1.22 (t, 3H, J=7.0 Hz); 13C NMR (100 MHz, CDCl3) δ 171.7, 168.7, 164.2, 142.6, 131.4, 129.6, 125.7, 114.1, 110.4, 108.0, 61.0, 56.0, 43.2, 35.1, 31.5, 14.3; IR (thin film) ν 3114, 2982, 2843, 1724, 1595, 1498, 1363, 1263, 1167, 1133, 1092, 1025 cm−1; HRMS (ESI) calcd for C20H21NO7S [M+Na]+ 494.1243, found 494.1265; >99% ee (3S,4S)-isomer as determined by HPLC (AD-H, 9:1 hexanes/i-PrOH), tr (3S,4S)=43.7 min, tr (3R,4R)=37.4 min.

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

Procedure: Prepared according to the general procedure from ethyl trans-4-oxo-2-butenoate and trans-N-(4-methoxybenzenesulfonyl)-1-(4-(3-iminoprop-1-enyl)phenyl)ethanone using 10 mol % 9 as the catalyst in 55% yield as a yellow oil. [α]D20 (c 1.22, CHCl3)=+168.2; 1H NMR (400 MHz, CDCl3) δ 8.04 (dd, 2H, J=6.9, 2.1 Hz), 7.59 (dd, 2H, J=6.5, 1.9 Hz), 7.19 (d, 1H, J=8.0 Hz), 7.07 (dd, 2H, J=6.9, 2.1 Hz), 6.69 (dd, 2H, J=6.6, 1.7 Hz), 5.59 (dd, 1H, J=8.0, 6.6 Hz), 4.14-4.11 (m, 2H), 3.95 (s, 3H), 3.74 (t, 1H, J=6.9 Hz), 3.58-3.53 (m, 1H), 2.58 (dd, 1H, J=17.4, 6.0 Hz), 2.52 (s, 3H), 1.90 (dd, 1H, J=17.4, 7.8 Hz), 1.22 (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 197.5, 171.5, 168.6, 164.5, 142.3, 136.6, 131.4, 128.9, 128.2, 125.3, 114.3, 112.7, 94.6, 61.1, 56.1, 43.9, 41.7, 31.4, 26.7, 14.3; IR (thin film) ν 3020, 2983, 2842, 1723, 1682, 1594, 1497, 1363, 1267, 1167, 1091, 1024 cm−1; HRMS (ESI) calcd for C24H25NO7S [M+Na]+ 494.1243, found 494.1265; >99% ee (3S,4S)-isomer as determined by HPLC(OD-H, 4:1 hexanes/i-PrOH), tr (3S,4S)=28.6 min, tr (3R,4R)=35.1 min. Prepared tr (3S,4S)=28.6 min, tr (3R,4R)=35.1 min.