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Synlett 2008(16): 2465-2470  
DOI: 10.1055/s-2008-1078219
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Generation of Arylcyclopenta-1,3-dienes from Cyclopenteno-spiro-benzosultams: Synthesis of 2-Arylnorbornenes

Helena Modrzejewska, Krzysztof Wojciechowski*
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O. Box 58, 01-224 Warszawa 42, Poland
Fax: +48(22)6326681; e-Mail: kris@icho.edu.pl;
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Publication History

Received 24 June 2008
Publication Date:
22 August 2008 (online)

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Abstract

Aza-ortho-xylylenes generated by thermal extrusion of sulfur dioxide from cyclopenteno-spiro-benzisothiazoline 2,2-dioxides undergo [1,5]-sigmatropic hydrogen shift leading to unstable arylcyclopentadienes that can be trapped with dienophiles to form arylnorbornenes.

Key words

cycloadditions - hydrogen shift - norbornene - extrusion - cyclopentadienes - metathesis - alkylation

14

Alkylation of Benzosultams with cis -1,4-Dichlorobut-2-ene - Typical Procedure
Benzosultam 1 (2 mmol) and cis-1,4-dichlorobut-2-ene (280 mg, 2.4 mmol) in DMSO (5 mL) were stirred with solid powdered NaOH (1 g) at r.t. until the starting material disappeared (TLC control, hexane-EtOAc, 2:1). Then the reaction mixture was poured into H2O (50 mL). The product was filtered dissolved in CH2Cl2 and dried over MgSO4. After evaporation of the solvent the product was recrystallized. The following compounds were obtained.
1,5-Dimethyl-1,3-dihydro-2,1-benzisothiazolo-3-spiro-4′-cyclopentene 2,2-Dioxide (2a)
Yield 53%; mp 107-109 ˚C (from EtOH); colorless crystals. ¹H NMR (500 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.72, 3.57, 5.82 (AA′MM′XX′, J AM = 15.7 Hz, 6 H), 3.11 (s, 3 H), 6.61 (d, J = 8.0 Hz, 1 H), 7.02 (d, J = 1.4 Hz, 1 H), 7.08 (dd, J = 8.0, 1.4 Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 20.94, 26.89, 41.84, 68.54, 109.01, 123.22, 128.08, 129.41, 129.78, 131.89, 137.51. IR (KBr): ν = 2925, 1616, 1612, 1494, 1467, 1447, 1313, 1272, 1184, 1144, 1136, 1064, 818 cm-¹. MS (EI, 70 eV): m/z (%) = 249 (82) [M+], 185 (61), 184 (65), 170 (100), 158 (31), 155 (20), 144 (46), 131 (31). HRMS: m/z calcd for C13H15NO2S: 249.0824; found: 249.0832. Anal. Calcd for C13H15NO2S: C, 62.62; H, 6.06; N, 5.62. Found: C, 62.62; H, 6.08; N, 5.55.
1-Methyl-5-methoxy-1,3-dihydro-2,1-benzisothiazolo-3-spiro-4′-cyclopentene 2,2-Dioxide (2b)
Yield 65%; mp 90-92 ˚C (from EtOH); pale yellow crystals. ¹H NMR (400 MHz, CDCl3): δ = 2.72, 3.57, 5.82 (AA′MM′XX′, J AM = 15.5 Hz, 6 H), 3.10 (s, 3 H), 3.77 (s, 3 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.81 (dd, J = 8.3, 2.6 Hz, 1 H), 6.84 (d, J = 2.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 27.27, 41.72, 55.77, 68.68, 109.64, 110.17, 113.54, 128.04, 131,13, 133.57, 155.39. IR (KBr): ν = 2935, 2840, 1591, 1495, 1457, 1446, 1435, 1307, 1288, 1274, 1149, 1135, 1028, 1012, 871, 826, 803, 762, 690 cm-¹. MS (EI, 70 eV): m/z (%) = 265 (37) [M+], 201(65), 200(20), 186 (100), 170(11), 160 (15), 158 (13), 155 (12), 147 (10), 143 (12). HRMS: m/z calcd for C13H15NO3S: 265.0773; found: 265.0774. Anal. Calcd for C13H15NO3S: C, 56.85; H, 5.70; N, 5.28. Found: C, 56.86; H, 5.62; N, 5.32.
5-Methyl-1-isopropyl-1,3-dihydro-2,1-benzisothiazolo-3-spiro-4′-cyclopentene 2,2-Dioxide (2c) Yield 70%; mp 126-127 ˚C (from EtOH); colorless crystals. ¹H NMR (400 MHz, CDCl3): δ = 1.54 (d, J = 7.2 Hz, 6 H), 2.29 (s, 3 H), 2.68, 3.56, 5.81 (AA′MM′XX′, J AM = 15.6 Hz, 6 H), 4.28 (sept, J = 7.2 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 7.01 (dd, J = 1.4, 1.0 Hz, 1 H), 7.05 (ddd, J = 8.2, 1.4, 1.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 20.26, 20.83, 42.03, 47.23, 68.69, 110.78, 123.50, 128.03, 129.06, 130.32, 131.25, 135.45. IR (KBr): ν = 3063, 2981, 2938, 2862, 1617, 1489, 1463, 1390, 1370, 1310, 1270, 1242, 1173, 1145, 1029, 999, 894, 810 cm-¹. MS (EI, 70 eV): m/z (%) = 277 (31) [M+], 213 (6), 198 (100), 183 (10), 182 (9), 170 (35), 155 (17), 144 (9), 128 (10). HRMS: m/z calcd for C15H19NO2S: 277.1137; found: 277.1127.
1-Methyl-1,3-dihydroisothiazolo[4,3- b ]pyridino-3-spiro-4′-cyclopentene 2,2-Dioxide (2d)
Yield 75%; mp 99-100 ˚C (from EtOH); colorless crystals. ¹H NMR (400 MHz, CDCl3): δ = 3.16 (s, 3 H), 3.02, 3.55, 5.83 (AA′MM′XX′, J AM = 16.7 Hz, 6 H), 6.97 (dd, J = 8.1, 1.3 Hz, 1 H), 7.22 (J = 8.1, 4.9 Hz, 1 H), 8.21 (dd, J = 4.9, 1.3 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 26.34, 40.59, 69.58, 115.37, 123.81, 127.85, 136.28, 142.73, 148.44. IR (KBr): ν = 3065, 2920, 1625, 1592, 1432, 1420, 1311, 1277, 1177, 1148, 1128, 1033, 948, 835, 798 cm-¹. MS (EI, 70 eV): m/z (%) = 236 (40) [M+], 172 (39), 171 (100), 157 (68), 156 (27), 145 (12), 131(13), 117 (9). HRMS: m/z calcd for C11H12N2O2S: 236.0619; found: 236.0614. Anal. Calcd for C11H12N2O2S: C, 55.91; H, 5.12; N, 11.86. Found: C, 56.11; H, 5.11; N, 11.96.
1-Methyl-4-nitro-1,3-dihydro-2,1-benzisothiazolo-3-spiro-4′-cyclopentene 2,2-Dioxide (2e) Yield 73%; mp 142-143 ˚C (from EtOH-EtOAc); pale yellow crystals. ¹H NMR (400 MHz, CDCl3): δ = 2.99, 3.59, 5.86 (AA′MM′XX′, J AM = 16.7 Hz, 2 H), 3.20 (s, 3 H), 6.98 (dd, J = 7.9, 1.0 Hz, 1 H), 7.48 (dd, J = 8.1, 8.1 Hz, 1 H), 7.58 (dd, J = 8.1, 1.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 27.22, 39.90, 69.49, 113.57, 118.05, 122.05, 128.40, 129.93, 142.13, 146.67. IR (KBr): ν = 3083, 2940, 1623, 1610, 1466, 1356, 1312, 1273, 1240, 1204, 1184, 1165, 1146, 1101, 918, 832, 804 cm-¹. MS (EI, 70 eV): m/z (%) = 280 (35) [M+], 236 (20), 215 (40), 199 (63), 198 (53), 184 (23), 169 (63), 168 (100), 159 (28), 154 (40), 144 (29), 143 (42), 130 (36), 128 (47), 115 (58). HRMS: m/z calcd for C12H12N2O4S: 280.0518; found: 280.0523. Anal. Calcd for C12H12N2O4S: C, 51.42; H, 4.32; N, 9.99. Found: C, 51.30; H, 4.32; N, 9.87.

15

Diallyl benzosultam 3b,e (1 mmol) and second-generation Grubbs catalyst (0.02 mmol) in CH2Cl2 (5 mL) were stirred under argon atmosphere until the starting material dis-appeared (TLC control). After completion of the reaction the catalyst was removed by passing the reaction mixture through short silica gel column, and after evaporation of the solvent the products were purified by crystallization from EtOH. The following compounds were obtained: 2b (yield 85%) and 2e (yield 73%).

16

Cycloaddition of Arylcyclopentadienes to Dienophiles - General Procedure
Spirocyclopentenosultam (2, 1 mmol) and dienophile (2 mmol) were refluxed in 1,2,4-trichlorobenzene (2 mL) for 15 min. The reaction mixture was subjected to column chromatography. Trichlorobenzene was eluted with hexane-EtOAc (100:1) and then the products were separated with hexane-EtOAc (4:1). The following compounds were formed:
Compound 7: ¹H NMR (500 MHz, DMSO-d 6,): δ = 1.64 (br d, J = 8.7 Hz, 1 H), 2.05 (br d, J = 8.7 Hz, 1 H), 2.17 (s, 3 H), 2.68 (d, J = 5.1 Hz, 3 H), 2.70 (dd, J = 9.8, 1.5 Hz, 1 H), 2.92 (dd, J = 9.8, 1.4 Hz, 1 H), 3.13 (m, 1 H), 3.31 (m, 1 H), 3.53 (s, 3 H), 3.57 (s, 3 H), 4.69 (q, J = 5.1 Hz, 1 H), 6.36 (d, J = 3.1 Hz, 1 H), 6.47 (br d, J = 8.3 Hz, 1 H), 6.85 (d, J = 1.8 Hz, 1 H), 6.92 (dd, J = 8.3, 1.8 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 19.95, 30.59, 43.90, 46.42, 46.94, 47.93, 49.01, 51.47, 51.55, 109.93, 119.94, 124.01, 127.89, 128.89, 132.39, 144.90, 147.34, 173.17, 173.23.
Compound 8: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.46 (br d, J = 8.6 Hz, 1 H), 1.64 (br d, J = 8.6 Hz, 1 H), 2.15 (s, 3 H), 2.65 (d, J = 5.2 Hz, 3 H), 3.10 (s, 3 H), 3.16 (dd, J = 10.1, 3.8 Hz, 1 H), 1 H), 3.37 (dd, J = 10.1, 3.4 Hz, 1 H), 3.38 (s, 3 H), 3.53 (m, 1 H), 3.57 (s, 3 H), 4.77 (q, J = 5.2 Hz, 1 H), 6.44 (d, J = 8.0 Hz, 1 H), 6.46 (d, J = 3.4 Hz, 1 H), 6.79 (d, J = 1.6 Hz, H), 6.87 (dd, J = 8.0, 1.6 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 20.00, 30.92, 46.22, 47.51, 47.61, 47.71, 50.54, 50.97, 51.11, 109.84, 121.27, 123.65, 128.29, 128.31, 131.70, 142.87, 145.09, 171.67, 173.30.
Compound 9: mp 140-142 ˚C (from EtOH); colorless crystals. ¹H NMR (500 MHz, DMSO-d 6): δ = 1.12 (d, J = 6.2 Hz, 3 H), 1.13 (d, J = 6.2 Hz, 3 H), 1.61 (br d, J = 9.7 Hz, 1 H), 1.88 (br dd, J = 9.7, 1.8 Hz, 1 H), 2.19 (s, 3 H), 2.96 (dd, J = 4.3, 1.9 Hz, 1 H), 3.53 (m, 1 H), 3.57 (dsept, J = 8.1, 6.2 Hz, 1 H), 3.70 (br s, 1 H), 3.76 (dd, J = 3.9, 3.8 Hz, 1 H), 4.12 (d, J = 8.1 Hz, 1 H), 6.44 (d, J = 3.1 Hz, 1 H), 6.61 (d, J = 8.3 Hz, 1 H), 6.96 (dd, J = 8.3, 1.7 Hz, 1 H), 6.98 (d, J = 1.7 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 19.87, 22.33, 22.37, 33.95, 35.01, 43.68, 45.93, 47.31, 51.64, 112.04, 119.01, 120.76, 120.77, 124.57, 128.95, 129.42, 129.65, 142.91, 147.48. IR (KBr): ν = 3381, 2962, 2239, 1614, 1513, 1312, 1280, 1179, 116, 852, 837, 802 cm-¹. MS (EI, 70 eV): m/z (%) = 291 (26) [M+], 276 (8), 213 (21), 212 (7), 199 (16), 198 (100), 182 (10), 170 (10), 158 (8). HRMS: m/z calcd for C19H21N3: 291.1736; found: 291.1745. Anal. Calcd for C19H21N3: C, 78.32; H, 7.26; N, 14.42. Found: C, 78.10; H, 7.35; N, 14.31.
Compound 10: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.13 (d, J = 6.3 Hz, 3 H), 1.18 (d, J = 6.2 Hz, 3 H), 1.31 (s, 3 H), 1.64 (br d, J = 8.2 Hz, 1 H), 1.82 (br d, J = 8.4 Hz, 1 H), 2.20 (s, 3 H), 2.49 (br s, 1 H), 3.12 (m, 1 H), 3.49 (br s, 1 H), 3.60 (m, 1 H), 4.09 (d, J = 8.2 Hz, 1 H), 6.62 (J = 3.1 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.92 (d, J = 1.6 Hz, 1 H), 6.96 (dd, J = 8.3, 1.6 Hz, 1 H), 7.29-7.34 (m, 2 H), 7.42-7.47 (m, 1 H), 7.48-7.53 (m, 2 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 19.83, 20.00, 22.42, 22.56, 43.74, 43.81, 50.57, 50.60, 52.71, 54.38, 112.05, 120.34, 124.55, 127.00, 128.25, 128.44, 128.89, 129.28, 130.97, 132.20, 142.94, 147.92, 176.16, 180.24. IR (KBr): ν = 3449, 2250, 2124, 1707, 1385, 1057, 1029, 1009, 822, 759 cm-¹. MS (EI, 70 eV): m/z (%) = 400(25) [M+], 385 (7), 213 (53), 198 (100), 182 (10), 170(11), 158 (4). HRMS: m/z calcd for C26H28N2O2: 400.2151; found: 400.2138.
Compound 11: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.45 (br d, J = 8.4 Hz, 1 H), 1.58 (br d, J = 8.4 Hz, 1 H), 2.62 (d, J = 5.3 Hz, 3 H), 3.08 (s, 3 H), 3.17 (m, 1 H), 3.37 (dd, J = 9.6, 3.2 Hz, 1 H), 3.55 (br d, J = 9.6 Hz, 1 H), 3.57 (s, 3 H), 3.58 (s, 3 H), 3.65 (s, 3 H), 4.58 (q, J = 5.3 Hz, 3 H), 6.47 (d, J = 8.7 Hz, 1 H), 6.50 (d, J = 3.1 Hz, 1 H), 6.63 (d, J = 3.0 Hz, 1 H), 6.70 (dd, J = 8.7, 3.0 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 31.38, 46.27, 46.87, 47.51, 47.62, 47.72, 50.63, 50.88, 55.35, 110.64, 113.09, 114.38, 130.02, 132.51, 141.85, 142.68, 150.35, 171.67, 173.30.
Compound 12: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.64 (br d, J = 8.7 Hz, 1 H), 2.05 (br d, J = 8.7 Hz, 1 H), 2.67 (d, J = 5.1 Hz, 3 H), 2.73 (dd, J = 9.7, 1.7 Hz, 1 H), 2.90 (dd, J = 9.7, 1.7 Hz, 1 H), 3.14 (m, 1 H), 3.30 (s, 3 H), 3.32 (m, 1 H), 3.58 (s, 3 H), 3.66 (s, 3 H), 4.49 (q, J = 5.1 Hz, 1 H), 6.41 (d, J = 3.2 Hz, 1 H), 6.51 (d, J = 8.8 Hz, 1 H), 6.65 (d, J = 3.0 Hz, 1 H), 6.76 (dd, J = 8.8, 3.0 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 31.02, 43.87, 46.36, 46.90, 47.87, 49.15, 51.44, 51.57, 55.33, 110.75, 113.38, 113.88, 121.02, 133.12, 141.62, 147.10, 150.44, 173.11, 173.21.
Compound 13: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.62 (br d, J = 9.7 Hz, 1 H), 1.91 (ddd, J = 9.7, 1.7, 1.7 Hz, 1 H), 2.69 (J = 5.0 Hz, 3 H), 3.06 (dd, J = 4.3, 1.9 Hz, 1 H), 3.51 (m, 1 H), 3.70 (s, 3 H), 3.72 (m, 1 H), 3.74 (dd, J = 4.3, 4.0 Hz, 1 H), 4.54 (d, J = 5.0 Hz, 1 H), 6.52 (d, J = 3.0 Hz, 1 H), 6.57 (d, J = 8.8 Hz, 1 H), 6.72 (d, J = 3.0 Hz, 1 H), 6.83 (dd, J = 8.8, 3.0 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 31.06, 33.87, 35.28, 46.06, 47.29, 51.31, 55.41, 111.27, 114.42, 114.46, 119.92, 120.63, 120.83, 130.50, 141.77, 147.16, 150.56. IR (KBr): ν = 2948, 2242, 1574, 1513, 1455, 1408, 1373, 1288, 1228, 1173, 1040, 948, 846, 810 cm-¹. MS (EI, 70 eV): m/z (%) = 279 (42) [M+], 201 (100), 186 (46), 160 (8). HRMS: m/z calcd for C17H17N3O: 279.1372; found: 279.1360.
Compound 14: Oil. ¹H NMR (500 MHz, DMSO-d 6): δ = 1.45 (br d, J = 8.6 Hz, 1 H), 1.49 (ddd, J = 8.6, 2.0, 2.0 Hz, 1 H), 2.68 (d, J = 4.9 Hz, 1 H), 3.15 (s, 3 H), 3.20 (m, 1 H), 3.38 (dd, J = 10.3, 3.3 Hz, 1 H), 3.45 (s, 3 H), 3.52 (dd, J = 10.3, 3.6 Hz, 1 H), 3.78 (br s, 1 H), 5.09 (q, J = 4.9 Hz, 1 H), 6.73 (d, J = 3.1 Hz, 1 H), 6.84 (dd, J = 8.2, 1.4 Hz, 1 H), 6.98 (dd, J = 8.2, 4.6 Hz, 1 H), 7.73 (dd, J = 4.6, 1.4 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 30.09, 46.44, 47.16, 47.43, 48.08, 50.18, 50.72, 51.08, 115.68, 122.12, 133.19, 135.74, 140.19, 143.49, 143.97, 171.78, 173.14. IR (KBr): ν = 3378, 2950, 2813, 1738, 1577, 1499, 1434, 1364, 1340, 1316, 1254, 1198, 1170, 1078, 1039, 913 cm-¹. MS (EI, 70 eV): m/z (%) = 316 (30) [M+], 301 (1), 285 (6), 257 (29), 225 (8), 217 (17), 197 (26), 185(15), 173 (16), 172 (71), 171 (100), 157(87), 145 (13), 131 (26), 113 (50). HRMS: m/z calcd for C17H20N2O4: 316.1423; found: 316.1418.
Compound 15: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.52 (ddd, J = 8.9, 1.7, 1.5 Hz, 1 H), 2.04 (br d, J = 8.9 Hz, 1 H), 2.68 (d, J = 4.9 Hz, 3 H), 2.76 (dd, J = 9.8, 1.6 Hz, 1 H), 2.85 (dd, J = 9.8, 1.7 Hz, 1 H), 3.19 (m, 1 H), 3.55 (s, 3 H), 3.56 (s, 3 H), 3.64 (m, 1 H), 5.12 (q, J = 4.9 Hz, 1 H), 6.68 (d, J = 3.3 Hz, 1 H), 6.89 (dd, J = 8.3, 1.3 Hz, 1 H), 7.05 (dd, J = 8.3, 4.5 Hz, 1 H), 7.82 (dd, J = 4.5, 1.3 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.88, 43.08, 47.01, 47.02, 47.82, 48.28, 51.49, 116.01, 122.59, 134.21, 136.01, 138.63, 143.53, 148.08, 173.10, 173.48. MS (EI, 70 eV): m/z (%) = 316 (44) [M+], 285 (12), 257 (19), 225 (6), 197 (15), 183 (10), 173 (28), 172 (98), 171 (100), 157(89), 145 (9), 131 (17). HRMS: m/z calcd for C17H20N2O4: 316.1423; found: 316.1431.
Compound 16: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.62 (br d, J = 9.8 Hz, 1 H), 1.80 (ddd, J = 9.8, 1.8, 1.8 Hz, 1 H), 2.75 (s, 3 H), 2.92 (dd, J = 4.5, 1.8 Hz, 1 H), 3.60 (m, 1 H), 3.79 (dd, J = 4.5, 3.7 Hz, 1 H), 3.97 (br s, 1 H), 5.23 (br s, 1 H), 6.83 (d, J = 3.1 Hz, 1 H), 7.01 (br d, J = 8.3 Hz, 1 H), 7.16 (dd, J = 8.3, 4.5 Hz, 1 H), 7.90 (dd, J = 4.5, 1.3 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.83, 34.15, 35.06, 44.99, 48.03, 51.14, 116.83, 120.49, 120.76, 123.40, 131.02, 135.98, 136.88, 143.82, 147.52.
Compound 17: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.57 (dd, J = 9.8 Hz, 1 H), 1.75 (ddd, J = 9.8, 1.6, 1.6 Hz, 1 H), 2.74 (s, 3 H), 3.14 (dd, J = 4.5, 1.8 Hz, 1 H), 3.52 (m, 1 H), 3.75 (dd, J = 4.0, 4.0 Hz, 1 H), 4.24 (m, 1 H), 5.29 (br s, 1 H), 6.80 (d, J = 3.4 Hz, 1 H), 7.02 (br d, J = 8.3 Hz, 1 H), 7.13 (dd, J = 8.3, 4.5 Hz, 1 H), 7.88 (dd, J = 4.5, 1.3 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.92, 33.37, 34.18, 45.39, 48.42, 49.24, 49.84, 116.80, 119.76, 120.80, 123.34, 131.06, 136.27, 136.89, 144.06, 147.57.
Compound 18: mp 198-200 ˚C (from EtOH-EtOAc); colorless crystals. ¹H NMR (500 MHz, DMSO-d 6): δ = 1.68 (br d, J = 8.6 Hz, 1 H), 1.84 (ddd, J = 8.6, 1.7, 1.7 Hz, 1 H), 2.72 (d, J = 4.9 Hz, 3 H), 3.51 (m, 1 H), 3.53 (dd, J = 7.8, 4.6 Hz, 1 H), 3.63 (dd, J = 7.8, 4.6 Hz, 1 H), 4.38 (m, 1 H), 5.01 (q, J = 4.9 Hz, 1 H), 6.75 (d, J = 3.2 Hz, 1 H), 6.85-6.88 (m, 2 H), 6.94 (dd, J = 8.3, 1.4 Hz, 1 H), 7.07 (dd, J = 8.3, 4.4 Hz, 1 H), 7.26-7.34 (m, 3 H), 7.84 (dd, J = 4.4, 1.4 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.84, 45.63, 46.33, 47.12, 47.22, 50.69, 116.62, 122.98, 126.90, 127.94, 128.48, 129.75, 132.29, 136.07, 137.07, 143.44, 145.93, 174.38, 176.56. IR (KBr): ν = 3439, 2881, 1768, 1703, 1582, 1495, 1379, 1179, 1161, 880, 757, 751, 725 cm-¹. MS (EI, 70 eV): m/z (%) = 345(37) [M+], 330 (3), 317 (2), 302(3), 198 (19), 197 (17), 185(9), 172 (90), 171(100), 157 (84), 156 (31), 145(15), 131 (21). HRMS: m/z calcd for C21H19N3O2: 345.1477; found: 345.1481.
Compound 21: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.64 (ddd, J = 8.5, 1.9, 1.9 Hz, 1 H), 1.79 (br d, J = 8.5 Hz, 1 H), 2.99 (dd, J = 3.5, 2.5 Hz, 1 H), 3.28 (m, 1 H), 3.31 (s, 3 H), 3.62 (dd, J = 3.5, 3.5 Hz, 1 H), 3.64 (s, 3 H), 6.16 (dd, J = 5.6, 2.8 Hz, 1 H), 6.52 (d, J = 5.6 Hz, 1 H), 7.37 (dd, J = 8.3, 4.7 Hz, 1 H), 7.54 (dd, J = 8.3, 1.2 Hz, 1 H), 8.27 (dd, J = 4.7, 1.2 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.12, 45.85, 47.30, 51.26, 51.73, 53.79, 57.16, 121.90, 122.95, 134.13, 135.57, 139.79, 142.74, 145.44, 169.31, 172.73.
Compound 22: ¹H NMR (500 MHz, DMSO-d 6): δ = 1.81 (br d, J = 8.5 Hz, 1 H), 2.08 (ddd, J = 8.5, 1.5, 1.5 Hz, 1 H), 2.70 (dd, J = 5.1, 1.3 Hz, 1 H), 3.24 (d, J = 5.1 Hz, 1 H), 3.26 (m, 1 H), 3.31 (s, 3 H), 3.67 (s, 3 H), 5.97 (d, J = 5.7 Hz, 1 H), 6.65 (dd, J = 5.7, 3.4 Hz, 1 H), 7.39 (dd, J = 8.2, 4.8 Hz, 1 H), 7.60 (dd, J = 8.2, 1.2 Hz, 1 H), 8.21 (dd, J = 4.8, 1.2 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.16, 47.97, 48.04, 48.70, 51.97, 56.04, 122.52, 122.91, 136.31, 137.23, 139.76, 142.23, 149.02, 168.87, 173.60.