3-(2-chlorophenyl)propanal

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

Procedure: To a solution of 964 mg (3.0 mmol) of 3-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]thiazolidine-2,4-dione and 738 mg (4.4 mmol) of 3-(2-chlorophenyl)-1-propanal in 20 ml of ethanol, 26 mg (0.3 mmol) of piperidine was added, followed by refluxing for 4.5 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with purified water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, chloroform/methanol=50/1) to yield 1.37 g (96.5%, yellow oily substance) of the desired product. by refluxing for 4.5 hours After the reaction mixture was cooled the solvent was distilled off The residue was dissolved in dichloromethane washed with purified water dried after which the solvent was distilled off The residue was purified by column chromatography (eluent, chloroform/methanol=50/1)

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

Procedure: Using the procedure of Stage B of Preparation 9, 1 g of the product of Stage B and 2.5 ml of triethylamine, 1.75 ml of dimethyl sulfoxide and 2.8 g of pyridinium sulfotrioxide complex were reacted to obtain after chromatography on silica, eluant: ethyl acetate-hexane (1-9), 425 mg (43%) of the desired product. were reacted to obtain after chromatography on silica, eluant

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

Procedure: Using the procedure of Stage B of Preparation 9, 1 g of the product of Stage B and 2.5 ml of triethylamine, 1.75 ml of dimethyl sulfoxide and 2.8 g of pyridinium sulfotrioxide complex were reacted to obtain after chromatography on silica, eluant: ethyl acetate-hexane (1-9), 425 mg (43%) of the desired product. were reacted to obtain after chromatography on silica, eluant

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

Procedure: To a solution of 964 mg (3.0 mmol) of 3-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]thiazolidine-2,4-dione and 738 mg (4.4 mmol) of 3-(2-chlorophenyl)-1-propanal in 20 ml of ethanol, 26 mg (0.3 mmol) of piperidine was added, followed by refluxing for 4.5 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with purified water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, chloroform/methanol=50/1) to yield 1.37 g (96.5%, yellow oily substance) of the desired product. by refluxing for 4.5 hours After the reaction mixture was cooled the solvent was distilled off The residue was dissolved in dichloromethane washed with purified water dried after which the solvent was distilled off The residue was purified by column chromatography (eluent, chloroform/methanol=50/1)

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

Procedure: To a solution of 964 mg (3.0 mmol) of 3-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]thiazolidine-2,4-dione and 738 mg (4.4 mmol) of 3-(2-chlorophenyl)-1-propanal in 20 ml of ethanol, 26 mg (0.3 mmol) of piperidine was added, followed by refluxing for 4.5 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with purified water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, chloroform/methanol=50/1) to yield 1.37 g (96.5%, yellow oily substance) of the desired product. by refluxing for 4.5 hours After the reaction mixture was cooled the solvent was distilled off The residue was dissolved in dichloromethane washed with purified water dried after which the solvent was distilled off The residue was purified by column chromatography (eluent, chloroform/methanol=50/1)

Conditions: temp:22.01; pressure:0.00; stir:

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

Procedure: Using the procedure of Stage B of Preparation 9, 1 g of the product of Stage B and 2.5 ml of triethylamine, 1.75 ml of dimethyl sulfoxide and 2.8 g of pyridinium sulfotrioxide complex were reacted to obtain after chromatography on silica, eluant: ethyl acetate - hexane (1-9), 425 mg (43%) of the desired product. were reacted to obtain after chromatography on silica, eluant

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

Procedure: Using the procedure of Stage B of Preparation 9, 1 g of the product of Stage B and 2.5 ml of triethylamine, 1.75 ml of dimethyl sulfoxide and 2.8 g of pyridinium sulfotrioxide complex were reacted to obtain after chromatography on silica, eluant: ethyl acetate - hexane (1-9), 425 mg (43%) of the desired product. were reacted to obtain after chromatography on silica, eluant

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-iodobenzene (700 mg), allyl alcohol (256 mg, 1.5 eq.), palladium acetate (13 mg, 0.02 eq), sodium bicarbonate (616 mg, 2.5 eq), and tetrabutylammonium chloride (816 mg, 1 eq) were mixed together in anhydrous DMF (12 mL). The mixture was stirred at 30° C. for 24 h, then diluted with water. The crude mixture was extracted into EtOAc 3×, and the organic layer was washed with water twice, then brine, and then dried over sodium sulfate, and concentrated. The residue was purified by chromatography (gradient: 88:12 hexanes:EtOAc to 1:1 hexanes:EtOAc) delivering the product (200 mg, 40% yield). 1H-NMR (300 MHz, CDCl3) δ 9.80 (s, 1H), 7.38-7.30 (m, 1H), 7.28-7.10 (m, 3H), 3.10-3.02 (m, 2H), 2.84-2.68 (m, 2H). The crude mixture was extracted into EtOAc 3× the organic layer was washed with water twice brine, and then dried over sodium sulfate concentrated The residue was purified by chromatography (gradient: 88:12 hexanes:EtOAc to 1:1 hexanes:EtOAc)

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

Procedure: Prepared according to the general procedure from 2-chloro-hydrocinnamaldehyde and (E)-ethyl 4-cyclohexyl-2-oxobut-3-enoate using 2 mol % 1 as the catalyst in 85% yield as a single diastereomer (colorless oil). [α]D20 (c 1.20, CHCl3)=+83.5; 1H NMR (400 MHz, CDCl3) δ 7.33-7.21 (m, 5H), 6.48 (d, 1H, J=6.5 Hz), 4.30 (dq, 1H, J=7.2, 1.8 Hz), 3.38 (dd, 1H, J=14.3, 5.7 Hz), 2.97-2.91 (m, 1H), 2.77 (dd, 1H, J=14.3, 9.1 Hz), 2.45-2.41 (m, 1H), 1.76-1.62 (m, 5H), 1.47-1.44 (m, 1H), 1.34 (t, 3H, J=7.2 Hz), 1.27-1.06 (m, 4H), 0.93-0.89 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.4, 160.7, 142.8, 138.6, 128.9, 126.9, 117.6, 62.0, 43.0, 39.4, 37.7, 31.7, 31.4, 27.2, 26.8, 26.1, 14.3; IR (thin film) ν 3520, 3086, 3028, 2981, 2928, 2853, 1770, 1731, 1660, 1453, 1369, 1309, 1262, 1120, 1094, 1013 cm−1; HRMS (ESI) calcd for C21H26O4 [M+Na]+ 365.1723, found 365.1721; 95% ee (4S,5S)-isomer as determined by HPLC (AS-H, 20:1 hexanes/i-PrOH), tr (4S,5S)=19.1 min, tr (4R,5R)=15.7 min. Prepared

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

Procedure: Prepared according to the general procedure from 2-chloro-hydrocinnamaldehyde and (E)-ethyl 2-oxo-4-p-tolylbut-3-enoate using 2 mol % 1 as the catalyst in 74% yield as a single diastereomer (colorless oil). [α]D2 (c 1.02, CHCl3)=+310.3; 1H NMR (400 MHz, CDCl3) δ 7.32-7.24 (m, 3H), 7.16-7.07 (m, 4H), 6.93-6.91 (m, 2H), 6.65 (d, 1H, J=6.8 Hz), 4.30 (q, 1H, J=7.1 Hz), 3.58 (t, 1H, J=6.7 Hz), 3.29-3.23 (m, 2H), 2.41 (dd, 1H, J=15.8, 10.9 Hz), 2.35 (s, 3H), 1.33 (t, 3H, J=7.1 Hz); 13C NMR (100 MHz, CDCl3) δ 168.9, 160.7, 142.1, 138.3, 132.8, 130.0, 129.1, 128.8, 128.4, 126.9, 118.9, 62.1, 45.0, 40.3, 32.1, 21.3, 14.3; IR (thin film) ν 3062, 3027, 2982, 2925, 1776, 1732, 1316, 1267, 1106 cm−1; HRMS (ESI) calcd for C22H22O4 [M+Na]+ 373.1410, found 373.1409; 97% ee (4S,5S)-isomer as determined by HPLC (AD-H, 9:1 hexanes/i-PrOH), tr (4S,5S)=21.7 min, tr (4R,5R)=13.4 min. Prepared

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

Procedure: Prepared according to the general procedure from 2-chloro-hydrocinnamaldehyde and (E)-methyl 4-oxo-4-furanylbut-2-enoate using 0.5 mol % 1 as the catalyst in 94% yield as an 8:1 mixture of diastereomers (brown oil). [α]D20 (c 1.03, CHCl3)=+119.5; 1H NMR (400 MHz, CDCl3) δ 7.41-7.29 (m, 4H), 7.18-7.16 (m, 2H), 6.67 (d, 1H, J=3.4 Hz), 6.47* (dd, 1H, J=3.2, 2.0 Hz), 6.45 (dd, 1H, J=3.2, 1.6 Hz), 5.74 (d, 1H, J=7.0 Hz), 5.70* (d, 1H, J=6.0 Hz), 3.77 (s, 3H), 3.68* (s, 3H), 3.55 (dd, 1H, J=14.3, 4.7 Hz), 3.52-3.46* (m, 1H), 3.40-3.35* (m. 1H), 3.29-3.26 (m, 1H), 3.15* (dd, 1H, J=13.6, 5.6 Hz), 3.03-2.97 (m, 1H), 2.90* (dd, 1H, J=13.6, 10.0 Hz), 2.74 (dd, 1H, J=14.3, 10.1 Hz); 13C NMR (100 MHz, CDCl3) δ 170.8, 168.4, 146.5, 145.3, 143.7, 138.0, 131.6, 129.6, 129.4, 128.9, 128.8, 127.4, 127.1, 111.8, 109.0, 108.9, 96.4, 94.0, 53.6, 52.9, 52.8, 43.0, 42.6, 40.8, 40.2, 35.5, 33.4; IR (thin film) ν 3063, 3029, 2953, 1781, 1734, 1495, 1455, 1264, 1225, 1201, 1174, 1085, 1009 cm−1; HRMS (ESI) calcd for C18H16O5 [M+Na]+ 335.0889, found 335.0890; 99% ee (3S,4S)-isomer as determined by HPLC (AD-H, 20:1 hexanes/i-PrOH), tr (3S,4S)=31.9 min, tr (3R,4R)=22.6 min. Prepared