A Novel One-Pot Reaction of Heterocyclic Ketene Aminals: Synthesis of a Small Library of Tetrahydropyridinone-Fused 1,3-Diazaheterocycles

Chu-Yi Yu; Peng-Hui Yang; Mei-Xin Zhao; Zhi-Tang Huang

doi:10.1055/s-2006-947343

LETTER

A Novel One-Pot Reaction of Heterocyclic Ketene Aminals: Synthesis of a Small Library of Tetrahydropyridinone-Fused 1,3-Diazaheterocycles

Chu-Yi Yu*^a, Peng-Hui Yang^a,b, Mei-Xin Zhao^a, Zhi-Tang Huang^a
^a Beijing National Laboratory for Molecular Science (BNLMS), Laboratory for Chemical Biology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, P. R. of China
Fax: +86(10)62554449; e-Mail: yucy@iccas.ac.cn;
^b Graduate University, Chinese Academy of Sciences, Beijing 100049, P. R. of China

Abstract

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Abstract

Inspired by the concept of multicomponent reactions, a novel one-pot reaction involving heterocyclic ketene aminals (HKAs), Meldrum’s acid and aldehydes has been developed and employed for the construction of a small library of tetrahydropyridinone-fused 1,3-diazaheterocycles.

Key words

one-pot reaction - heterocyclic ketene aminals - tetrahydropyridinones - 1,3-diazaheterocycles - synthesis

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References

References and Notes

1a Muegge I. Chem. Eur. J. 2002, 8: 1977

1b Bemis GW. Murcko MA. J. Med. Chem. 1996, 39: 2887

1c De Laet A. Hehenkamp JJJ. Wife RL. J. Heterocycl. Chem. 2000, 37: 669

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2a Multicomponent Reactions Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005.

2b Simon C. Constantieux T. Rodriguez J. Eur. J. Org. Chem. 2004, 24: 4957

2c Ramón DJ. Yus M. Angew. Chem. Int. Ed. 2005, 44: 1602

2d Orru RVA. de Greef M. Synthesis 2003, 1471

2e Dömling A. Chem. Rev. 2006, 106: 17

2f Kappe CO. Acc. Chem. Res. 2000, 33: 879

3 Armstrong RW. Combs AP. Tempest PA. Brown SD. Keating TA. Acc. Chem. Res. 1996, 29: 123

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4a Huang Z.-T. Wang M.-X. Heterocycles 1994, 37: 1233

4b Huang Z.-T. Wang M.-X. Prog. Natural Sci. 2002, 12: 249

5a Huang Z.-T. Tzai L.-H. Chem. Ber. 1986, 119: 2208

5b Zhang J.-H. Wang M.-X. Huang Z.-T. J. Chem. Soc., Perkin Trans. 1 1999, 321

5c Yu C.-Y. Wang L.-B. Huang Z.-T. Synthesis 1996, 959

5d Zhang J.-H. Wang M.-X. Huang Z.-T. J. Chem. Soc., Perkin Trans. 1 1999, 2087

5e Nie X.-P. Wang M.-X. Huang Z.-T. Synthesis 2000, 1439

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6a Chen BC. Heterocycles 1991, 32: 529

6b McNab H. Chem. Soc. Rev. 1978, 7: 345

6c Gaber AEM. McNab H. Synthesis 2001, 2059

7

General Procedure for the Three-Component Reaction.
Et₃N (about 0.4 mmol, 0.2 equiv) was added to a solution of heterocyclic ketene aminals 1 or 2 (2.0 mmol), Meldrum’s acid (3, 2.4 mmol) and aldehyde (2.4 mmol) in about 30 mL of dry MeCN. The reaction mixture was refluxed for a certain period of time (Table [1] and Table [2] ). The solvent was removed under vacuum and the residue was subjected to either recrystallization (EtOAc) or column chromatography on silical gel to afford the product.
Compound 5a: white crystals; mp 166-167 °C; R _f = 0.48 (EtOAc). IR (KBr): 2971, 1690, 1634, 1393, 1269, 912 cm^-1. ¹H NMR (CDCl₃): δ = 2.78 (dd, J = 2.1, 16.5 Hz, 1 H), 2.98 (dd, J = 6.6, 16.5 Hz, 1 H), 3.84-3.95 (m, 3 H), 4.10-4.15 (m, 2 H), 7.01-7.31 (m, 10 H), 9.73 (s, 1 H). ¹³C NMR (CDCl₃): δ = 38.16, 40.85, 41.89, 42.81, 88.43, 126.47, 126.70, 126.80, 127.91, 128.80, 129.18, 141.22, 144.00, 157.38, 168.06, 192.20. MS (EI): m/z (%) = 318 (100) [M⁺], 241 (52), 213 (54), 105 (22). Anal. Calcd for C₂₀H₁₈N₂O₂: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.44; H, 5.79; N, 8.73.
Compound 5b: white crystals; mp 180-181 °C; R _f = 0.38 (EtOAc). IR (KBr): 3285, 1698, 1620, 1370, 1011 cm^-1. ¹H NMR (CDCl₃): δ = 2.78 (dd, J = 1.8, 16.2 Hz, 1 H), 2.97 (dd, J = 6.9, 16.2 Hz, 1 H), 3.86-3.98 (m, 3 H), 4.06 (dd, J = 1.8, 6.9 Hz, 1 H), 4.09-4.15 (m, 1 H), 7.02-7.29 (m, 9 H), 9.73 (s, 1 H). ¹³C NMR (CDCl₃): δ = 38.24, 40.92, 41.92, 42.85, 88.29, 126.68, 126.98, 128.02, 128.14, 128.94, 135.15, 139.58, 143.81, 157.65, 167.86, 190.72. MS (EI): m/z (%) = 352 (100) [M⁺], 275 (63), 213 (66), 139 (32). Anal. Calcd for C₂₀H₁₇ClN₂O₂: C, 68.09; H, 4.86; N, 7.94. Found: C, 67.85; H, 4.93; N, 7.74.
Compound 5c: white crystals; mp 172-174 °C; R _f = 0.52 (EtOAc). IR (KBr): 3282, 1694, 1629, 1014, 703 cm^-1. ¹H NMR (CDCl₃): δ = 2.26 (s, 3 H), 2.55 (dd, J = 1.8, 16.2 Hz, 1 H), 3.06 (dd, J = 6.9, 16.2 Hz, 1 H), 3.69-3.78 (m, 3 H), 3.88-3.97 (m, 1 H), 4.06 (d, J = 5.4 Hz, 1 H), 7.01-7.28 (m, 9 H), 9.62 (s, 1 H).¹³C NMR (DMSO-d ₆): δ = 20.80, 37.71, 40.50, 41.51, 42.73, 87.01, 126.30, 126.35, 126.50, 128.19, 128.54, 138.23, 139.11, 144.81, 156.49, 167.64, 189.52. MS (EI): m/z (%) = 332 (80) [M⁺], 331 (100), 304 (21), 255 (36), 213 (42), 119 (25). Anal. Calcd for C₂₁H₂₀N₂O₂: C, 75.88; H, 6.06; N, 8.43. Found: C, 75.78; H, 6.12; N, 8.55.
Compound 5d: white crystals; mp 192-194 °C; R _f = 0.36 (EtOAc). IR (KBr): 1690, 1633, 1598, 1171, 911 cm^-1. ¹H NMR (CDCl₃): δ = 2.80 (dd, J = 2.1, 16.5 Hz, 1 H), 2.97 (dd, J = 6.6, 16.5 Hz, 1 H), 3.78 (s, 3 H), 3.82-3.93 (m, 3 H), 4.08-4.15 (m, 1 H), 4.20 (dd, J = 2.1, 6.6 Hz, 1 H), 6.73-6.78 (m, 2 H), 7.07-7.30 (m, 7 H), 9.73 (s, 1 H). ¹³C NMR (CDCl₃): δ = 38.32, 40.96, 41.86, 42.78, 55.25, 88.36, 113.14, 126.78, 126.82, 128.54, 128.86, 133.74, 143.96, 157.36, 160.47, 168.11, 191.40. MS (EI): m/z (%) = 348 (47) [M⁺], 320 (27), 271 (20), 213 (28), 135 (28). Anal. Calcd for C₂₁H₂₀N₂O₃: C, 72.40; H, 5.79; N, 8.04. Found: C, 72.39; H, 5.89; N, 7.93.
Compound 5e: white crystals; mp 177-179 °C; R _f = 0.20 (EtOAc). IR (KBr): 3301, 1692, 1646, 1544, 980 cm^-1. ¹H NMR (CDCl₃): δ = 1.96 (s, 3 H), 2.80 (dd, J = 1.8, 16.5 Hz, 1 H), 3.03 (dd, J = 7.8, 16.5 Hz, 1 H), 3.77-3.90 (m, 3 H), 3.97-4.06 (m, 1 H), 4.15 (dd, J = 1.8, 7.8 Hz, 1 H), 7.10-7.30 (m, 5 H), 9.28 (s, 1 H). ¹³C NMR (CDCl₃): δ = 26.43, 38.29, 40.73, 41.78, 42.58, 88.30, 126.65, 126.98, 128.88, 143.53, 155.27, 167.65, 194.47. MS (EI): m/z (%) = 256 (93) [M⁺], 213 (100), 179 (90). Anal. Calcd for C₁₅H₁₆N₂O₂: C, 70.29; H, 6.29; N, 10.93. Found: C, 69.92; H, 6.35; N, 10.86. Compound 5f: white crystals; mp 135-136 °C; R _f = 0.61 (EtOAc). IR (KBr): 3381, 1672, 1604, 1440, 1367, 1120, 1039, 734 cm^-1. ¹H NMR (CDCl₃): δ = 1.17 (t, J = 7.1 Hz, 3 H), 2.77 (dd, J = 1.9, 16.7 Hz, 1 H), 2.94 (dd, J = 7.8, 16.7 Hz, 1 H), 3.63-3.89 (m, 3 H), 3.99-4.15 (m, 3 H), 4.19 (dd, J = 1.7, 7.8 Hz, 1 H), 7.14-7.19 (m, 3 H), 7.22-7.27 (m, 2 H), 7.40 (s, 1 H). ¹³C NMR (DMSO-d ₆): δ = 14.57, 35.76, 41.85, 42.27, 58.06, 59.72, 75.24, 126.13, 126.30, 128.32, 145.30, 153.74, 167.04, 167.73. MS (ESI): m/z = 287 [M + H⁺]. Anal. Calcd for C₁₆H₁₈N₂O₃: C, 67.12; H, 6.34; N, 9.78. Found: C, 66.86; H, 6.22; N, 9.91.
Compound 6a: white crystals; mp 167-168 °C; R _f = 0.60 (EtOAc). IR (KBr): 3292, 2967, 1701, 1609, 1536, 1147, 910cm^-1. ¹H NMR (CDCl₃): δ = 2.02-2.10 (m, 2 H), 2.81 (dd, J = 2.4, 15.6 Hz, 1 H), 2.95 (dd, J = 6.3, 15.6 Hz, 1 H), 3.46-3.60 (m, 3 H), 3.95 (dd, J = 2.4, 6.3 Hz, 1 H), 3.98-4.06 (m, 1 H), 7.03-7.29 (m, 10 H), 12.98 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.82, 36.95, 38.71, 38.87, 40.51, 89.90, 126.19, 126.69, 126.84, 127.85, 128.53, 128.71, 141.95, 143.52, 156.86, 168.97, 190.13. MS (EI): m/z (%) = 332 (89) [M⁺], 304 (26), 255 (56), 227 (100). Anal. Calcd for C₂₁H₂₀N₂O₂: C, 75.88; H, 6.06; N, 8.43. Found: C, 76.21; H, 6.07; N, 8.48.
Compound 6b: white crystals; mp 189-190 °C; R _f = 0.56 (EtOAc). IR (KBr): 1701, 1609, 1536, 1146 cm^-1. ¹H NMR (CDCl₃): δ = 2.03-2.11 (m, 2 H), 2.82 (dd, J = 2.4, 15.9 Hz, 1 H), 2.95 (dd, J = 6.3, 15.9 Hz, 1 H), 3.47-3.62 (m, 3 H), 3.90 (dd, J = 2.4, 6.3 Hz, 1 H), 3.98-4.07 (m, 1 H), 7.01-7.30 (m, 9 H), 12.95 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.76, 37.04, 38.74, 38.88, 40.52, 89.86, 126.80, 126.87, 127.75, 128.06, 128.85, 134.44, 140.29, 143.31, 157.07, 168.76, 188.60. MS (EI): m/z (%) = 366 (85) [M⁺], 338 (19), 289 (56), 227 (100), 139 (18). Anal. Calcd for C₂₁H₁₉ClN₂O₂: C, 68.76; H, 5.22; N, 7.64. Found: C, 68.78; H, 5.28; N, 7.58.
Compound 6c: white crystals; mp 218-220 °C; R _f = 0.62 (EtOAc). IR (KBr): 1700, 1608, 1536, 1146, 911 cm^-1. ¹H NMR (CDCl₃): δ = 2.03-2.09 (m, 2 H), 2.30 (s, 3 H), 2.81 (dd, J = 2.4, 15.9 Hz, 1 H), 2.95 (dd, J = 6.3, 15.9 Hz, 1 H), 3.50-3.58 (m, 3 H), 3.98-4.06 (m, 2 H), 7.01-7.28 (m, 9 H), 13.01 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.85, 21.29, 36.98, 38.70, 38.87, 40.54, 89.93, 126.30, 126.66, 126.88, 128.45, 128.71, 138.50, 139.16, 143.56, 156.79, 169.03, 190.20. MS (EI): m/z (%) = 346 (100) [M⁺], 318 (32), 269 (53), 227 (100). Anal. Calcd for C₂₂H₂₂N₂O₂: C, 76.28; H, 6.40; N, 8.09. Found: C, 76.40; H, 6.53; N, 8.03.
Compound 6d: white crystals; mp 170-172 °C; R _f = 0.58 (EtOAc). IR (KBr): 3292, 1700, 1604, 1527, 1170, 911 cm^-1. ¹H NMR (CDCl₃): δ = 2.01-2.09 (m, 2 H), 2.83 (dd, J = 2.4, 15.9 Hz, 1 H), 2.96 (dd, J = 6.0, 15.9 Hz, 1 H), 3.48-3.60 (m, 3 H), 3.76 (s, 3 H), 3.98-4.07 (m, 2 H), 6.71-7.30 (m, 9 H), 13.04 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.86, 37.11, 38.70, 38.89, 40.60, 55.24, 89.93, 113.09, 126.71, 126.91, 128.09, 128.77, 134.58, 143.54, 156.81, 159.90, 169.03, 189.64. MS (EI): m/z (%) = 362 (100) [M⁺], 334 (57), 285 (47), 227 (96), 135 (30). Anal. Calcd for C₂₂H₂₂N₂O₃: C, 72.91; H, 6.12; N, 7.73. Found: C, 72.94; H, 6.23; N, 7.63.
Compound 6e: white crystals; mp 142-143 °C; R _f = 0.42 (EtOAc). IR (KBr): 2964, 1698, 1615, 1560, 1180, 927, 728 cm^-1. ¹H NMR (CDCl₃): δ = 1.98-2.02 (m, 5 H), 2.87 (dd, J = 2.1, 15.6 Hz, 1 H), 3.01 (dd, J = 6.9, 15.6 Hz, 1 H), 3.38-3.59 (m, 3 H), 3.93-4.01 (m, 1 H), 4.08 (dd, J = 2.1, 6.9 Hz, 1 H), 7.08-7.30 (m, 5 H), 12.50 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.83, 26.66, 36.86, 38.52, 38.82, 40.20, 89.52, 126.76, 126.88, 128.78, 142.75, 155.06, 168.78, 191.99. MS (EI): m/z (%) = 270 (64) [M⁺], 227 (100), 193 (74). Anal. Calcd for C₁₆H₁₈N₂O₂: C, 71.09; H, 6.71; N, 10.36. Found: C, 71.09; H, 6.73; N, 10.28.
Compound 5g: white crystals; mp 198-199 °C; R _f = 0.54 (EtOAc). IR (KBr): 1701, 1611, 1524, 1348, 1148, 910 cm^-1. ¹H NMR (CDCl₃): δ = 2.75 (dd, J = 1.8, 16.5 Hz, 1 H), 3.05 (dd, J = 7.2, 16.5 Hz, 1 H), 3.86-3.97 (m, 3 H), 4.08-4.18 (m, 1 H), 4.23 (dd, J = 1.8, 7.2 Hz, 1 H), 7.08-7.17 (m, 4 H), 7.22-7.36 (m, 3 H), 8.08-8.11 (m, 2 H), 9.74 (s, 1 H). ¹³C NMR (CDCl₃): δ = 38.31, 40.17, 42.00, 42.85, 87.24, 124.10, 126.15, 127.65, 128.15, 129.40, 140.99, 146.84, 151.81, 157.17, 167.13, 192.16. MS (EI): m/z (%) = 363 (100) [M⁺], 258 (53), 241 (48), 228 (17), 212 (17). Anal. Calcd for C₂₀H₁₇N₃O₄: C, 66.11; H, 4.72; N, 11.56. Found: C, 65.85; H, 4.74; N, 11.46.
Compound 5h: yellow crystals; mp 208-210 °C; R _f = 0.30 (EtOAc). IR (KBr): 3290, 1696, 1633, 1524, 1018, 912 cm^-1. ¹H NMR (CDCl₃): δ = 2.85 (dd, J = 2.1, 17.1 Hz, 1 H), 3.10 (dd, J = 8.1, 17.1 Hz, 1 H), 3.89-4.01 (m, 3 H), 4.08-4.22 (m, 1 H), 4.65 (dd, J = 2.1, 8.1 Hz, 1 H), 6.87-6.90 (m, 2 H), 7.15-7.37 (m, 5 H), 7.49-7.55 (m, 1 H), 7.76 (dd, J = 1.2, 8.1 Hz, 1 H), 9.72 (s, 1 H). ¹³C NMR (CDCl₃): δ = 34.22, 39.46, 42.04, 42.90, 87.83, 124.94, 125.38, 127.92, 128.13, 128.89, 129.23, 133.39, 139.51, 140.88, 148.39, 157.58, 167.35, 192.91. MS (EI): m/z (%) = 363 (2) [M⁺], 225 (100), 196 (24), 155 (30), 105 (27). Anal. Calcd for C₂₁H₁₇N₃O₄: C, 66.11; H, 4.72; N, 11.56. Found: C, 66.02; H, 4.76; N, 11.59.
Compound 5i: white crystals; mp 190-191 °C; R _f = 0.44 (EtOAc). IR (KBr): 3284, 1695, 1630, 1522, 1371, 1015, 911 cm^-1. ¹H NMR (CDCl₃): δ = 2.73 (dd, J = 2.1, 16.5 Hz, 1 H), 2.96 (dd, J = 6.9, 16.5 Hz, 1 H), 3.83-3.94 (m, 3 H), 4.05-4.14 (m, 2 H), 6.94-6.97 (m, 1 H), 7.12-7.15 (m, 2 H), 7.19-7.35 (m, 5 H), 9.73 (s, 1 H). ¹³C NMR (CDCl₃): δ = 37.67, 40.71, 41.90, 42.81, 87.97, 126.31, 127.99, 128.11, 128.93, 129.27, 132.53, 141.11, 142.57, 157.24, 167.71, 192.12. MS (EI): m/z (%) = 352 (100) [M⁺], 324 (18), 247 (64), 241 (50). Anal. Calcd for C₂₀H₁₇ClN₂O₂: C, 68.09; H, 4.86; N, 7.94. Found: C, 67.64; H, 4.81; N, 7.65.
Compound 5j: white crystal; mp 189-190 °C; R _f = 0.40 (EtOAc). IR (KBr): 3282, 1695, 1631, 1371, 911 cm^-1. ¹H NMR (CDCl₃): δ = 2.78 (dd, J = 2.1, 16.5 Hz, 1 H), 2.91 (dd, J = 7.2, 16.5 Hz, 1 H), 3.85-4.01 (m, 3 H), 4.08-4.17 (m, 1 H), 4.49 (dd, J = 2.1, 7.2 Hz, 1 H), 7.03-7.06 (m, 2 H), 7.11-7.35 (m, 7 H), 9.79 (s, 1 H). ¹³C NMR (CDCl₃): δ = 35.63, 38.59, 41.93, 42.92, 87.59, 126.03, 127.25, 127.99, 128.37, 129.26, 130.18, 133.07, 140.90, 157.87, 167.81, 192.16. MS (EI): m/z (%) = 352 (14) [M⁺], 317 (100), 241 (22). Anal. Calcd for C₂₀H₁₇ClN₂O₂: C, 68.09; H, 4.86; N, 7.94. Found: C, 68.26; H, 4.72; N, 7.65.
Compound 5k: white crystals; mp 228-230 °C; R _f = 0.43 (EtOAc). IR (KBr): 3252, 1694, 1530, 1374, 1104, 913 cm^-1. ¹H NMR (CDCl₃): δ = 2.75-2.89 (m, 2 H), 3.70 (s, 3 H), 3.80-3.98 (m, 3 H), 4.05-4.15 (m, 1 H), 3.80-3.98 (m, 3 H), 4.05-4.15 (m, 1 H), 4.42 (dd, J = 3.3, 5.7 Hz, 1 H), 6.81-6.87 (m, 2 H), 6.95-6.98 (dd, J = 1.2, 7.5 Hz, 1 H), 7.09-7.31 (m, 6 H), 9.78 (s, 1 H). ¹³C NMR (CDCl₃): δ = 32.66, 38.66, 41.84, 42.84, 55.22, 87.99, 110.64, 120.56, 126.41, 127.40, 127.73, 128.08, 129.04, 131.72, 141.29, 156.41, 157.93, 168.77, 191.98. MS (EI): m/z (%) = 348 (62) [M⁺], 317 (41), 299 (20), 243 (100). Anal. Calcd for C₂₁H₂₀N₂O₃: C, 72.40; H, 5.79; N, 8.04. Found: C, 72.22; H, 5.97; N, 8.05.
Compound 5l: white crystals; mp 183-184 °C; R _f = 0.36 (EtOAc). IR (KBr): 1688, 1633, 1386, 1030, 914 cm^-1. ¹H NMR (CDCl₃): δ = 2.75 (dd, J = 2.1, 16.5 Hz, 1 H), 2.94 (dd, J = 6.6, 16.5 Hz, 1 H), 3.78 (s, 3 H), 3.83-3.94 (m, 3 H), 4.06 (dd, J = 2.1, 6.6 Hz, 1 H), 4.08-4.13 (m, 1 H), 6.77-6.81 (m, 2 H), 6.92-6.97 (m, 2 H), 7.16-7.34 (m, 5 H), 9.71 (s, 1 H). ¹³C NMR (CDCl₃): δ = 37.38, 41.07, 41.89, 42.81, 55.25, 88.79, 114.15, 126.50, 127.75, 127.90, 129.19, 136.01, 141.26, 157.32, 158.36, 168.19, 192.15. MS (EI): m/z (%) = 348 (97) [M⁺], 243 (100). Anal. Calcd for C₂₁H₂₀N₂O₃: C, 72.40; H, 5.79; N, 8.04. Found: C, 72.28; H, 5.82; N, 8.04.
Compound 6f: yellow crystals; mp 197-198 °C; R _f = 0.57 (EtOAc). IR (KBr): 1700, 1613, 1523, 1151 cm^-1. ¹H NMR (CDCl₃): δ = 2.09-2.17 (m, 2 H), 2.89 (dd, J = 1.8, 16.5 Hz, 1 H), 3.05 (dd, J = 7.5, 16.5 Hz, 1 H), 3.48-3.72 (m, 3 H), 4.05-4.14 (m, 1 H), 4.47 (dd, J = 1.8, 7.5 Hz, 1 H), 6.79-6.82 (m, 2 H), 7.12-7.38 (m, 5 H), 7.50-7.56 (m, 1 H), 7.78 (dd, J = 1.2 Hz, 1 H), 12.86 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.76, 33.38, 38.73, 38.95, 89.43, 125.03, 125.14, 127.89, 128.10, 128.59, 129.06, 133.34, 139.32, 141.51, 148.42, 157.04, 168.43, 191.27. MS (ESI): m/z (%) = 378 [M + H⁺]. Anal. Calcd for C₂₁H₁₉N₃O₄: C, 66.83; H, 5.07; N, 11.13. Found: C, 66.63; H, 5.17; N, 10.90.
Compound 6g: white crystals; mp 181-183 °C; R _f = 0.64 (EtOAc). IR (KBr): 1702, 1610, 1538, 1146, 735 cm^-1. ¹H NMR (CDCl₃): δ = 2.01-2.09 (m, 2 H), 2.76 (dd, J = 2.1, 15.9 Hz, 1 H), 2.95 (dd, J = 6.3, 15.9 Hz, 1 H), 3.45-3.59 (m, 3 H), 3.92 (dd, J = 2.1, 6.3 Hz, 1 H), 3.97-4.06 (m, 1 H), 6.97-7.00 (m, 5 H), 7.06-7.09 (m, 2 H), 7.18-7.30 (m, 5 H), 12.94 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.76, 36.49, 38.70, 38.90, 40.37, 89.46, 126.05, 127.95, 128.27, 128.63, 28.88, 132.46, 141.82, 142.12, 156.74, 168.64, 190.17. MS (EI): m/z (%) = 366 (86) [M⁺], 338 (18), 261 (100), 255 (45). Anal. Calcd for C₂₁H₁₉ClN₂O₂: C, 68.76; H, 5.22; N, 7.64. Found: C, 68.49; H, 5.25; N, 7.49.
Compound 6h: white crystals; mp 190-191 °C; R _f = 0.63 (EtOAc). IR (KBr): 1701, 1612, 1538, 1150, 909 cm^-1. ¹H NMR (CDCl₃): δ = 2.07-2.15 (m, 2 H), 2.79-2.93 (m, 2 H), 3.48-3.67 (m, 3 H), 4.01-4.10 (m, 1 H), 4.28 (dd, J = 3.0, 6.0 Hz, 1 H), 6.94-6.96 (m, 2 H), 7.13-7.32 (m, 7 H), 12.98 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.85, 34.76, 37.99, 38.73, 38.91, 89.30, 125.65, 127.13, 127.94, 128.17, 128.27, 128.56, 130.09, 133.18, 140.64, 141.68, 157.19, 168.74, 190.49. MS (EI): m/z (%) = 366 (23) [M⁺], 331 (100), 313 (25), 261 (31), 255 (32). Anal. Calcd for C₂₁H₁₉ClN₂O₂: C, 68.76; H, 5.22; N, 7.64. Found: C, 68.35; H, 5.31; N, 7.44.
Compound 6i: white crystals; mp 207-208 °C; R _f = 0.67 (EtOAc). IR (KBr): 1700, 1608, 1536, 1146, 907 cm^-1. ¹H NMR (CDCl₃): δ = 2.30 (s, 3 H), 2.80 (dd, J = 2.4, 15.6 Hz, 1 H), 2.93 (dd, J = 6.0, 15.6 Hz, 1 H), 3.43-3.62 (m, 3 H), 3.92 (dd, J = 2.4, 6.0 Hz, 1 H), 3.96-4.05 (m, 1 H), 6.92-7.30 (m, 5 H), 13.00 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.82, 21.00, 36.51, 38.71, 38.85, 40.62, 90.10, 126.25, 126.71, 127.84, 128.52, 129.42, 136.16, 140.37, 141.98, 156.86, 169.10, 189.98. MS (EI): m/z (%) = 346 (84) [M⁺], 318 (22), 255 (36), 241 (100). Anal. Calcd for C₂₂H₂₂N₂O₂: C, 76.28; H, 6.40; N, 8.09. Found: C, 76.16; H, 6.46; N, 8.13.
Compound 6j: white crystals; mp 212-213 °C; R _f = 0.55 (EtOAc). IR (KBr): 1699, 1609, 1536, 1146, 908 cm^-1. ¹H NMR (CDCl₃): δ = 2.06-2.10 (m, 2 H), 2.75-2.90 (m, 2 H), 3.49-3.63 (m, 3 H), 3.66 (s, 3 H), 3.98-4.07 (m, 1 H), 4.23 (dd, J = 3.0, 5.7 Hz, 1 H), 6.78-6.89 (m, 2 H), 7.01-7.06 (m, 3 H), 7.13-7.26 (m, 4 H), 13.03 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.91, 31.64, 38.18, 38.73, 38.81, 55.19, 89.81, 110.65, 120.52, 126.05, 127.51, 127.63, 128.01, 128.35, 131.40, 142.03, 156.54, 157.36, 169.63, 189.98. MS (EI): m/z (%) = 362 (54) [M⁺], 331 (32), 257 (100). Anal. Calcd for C₂₂H₂₂N₂O₃: C, 72.91; H, 6.12; N, 7.73. Found: C, 72.75; H, 6.16; N, 7.77.
Compound 6k: white crystals; mp 163-165 °C; R _f = 0.61 (EtOAc). IR (KBr): 1699, 1610, 1536, 1147 cm^-1. ¹H NMR (CDCl₃): δ = 2.03-2.11 (m, 2 H), 2.80 (dd, J = 6.3, 16.2 Hz, 1 H), 2.90 (dd, J = 2.4, 16.2 Hz, 1 H), 3.44-3.63 (m, 3 H), 3.97-4.06 (m, 1 H), 4.31 (dd, J = 2.4, 6.3 Hz, 1 H), 4.92 (dd, J = 12.3, 39.6 Hz, 2 H), 6.78-7.33 (m, 14 H), 12.98 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.90, 31.73, 38.32, 38.72, 38.83, 69.73, 89.71, 111.92, 120.78, 125.98, 127.00, 127.62, 127.72, 127.74, 127.98, 128.31, 128.46, 131.61, 137.08, 142.17, 155.57, 157.36, 169.61, 190.17. MS (EI): m/z (%) = 438 (25) [M⁺], 410 (19), 333 (100), 242 (18). Anal. Calcd for C₂₈H₂₆N₂O₃: C, 76.69; H, 5.98; N, 6.39. Found: C, 76.50; H, 6.07; N, 6.45.
Compound 6l: white crystals; mp 169-170 °C; R _f = 0.52 (EtOAc). IR (KBr): 1698, 1607, 1537, 1145, 1028, 733, 701 cm^-1. ¹H NMR (CDCl₃): δ = 2.01-2.09 (m, 2 H), 2.78 (dd, J = 2.4, 15.6 Hz, 1 H), 2.92 (dd, J = 6.0, 15.6 Hz, 1 H), 3.44-3.62 (m, 3 H), 3.77 (s, 3 H), 3.90 (dd, J = 2.4, 6.0 Hz, 1 H), 3.97-4.06 (m, 1 H), 6.76-6.81 (m, 2 H), 6.94-7.00 (m, 2 H), 7.10-7.30 (m, 5 H), 12.97 (s, 1 H). ¹³C NMR (CDCl₃): δ = 20.83, 36.16, 38.70, 38.84, 40.67, 55.21, 90.28, 114.09, 126.21, 127.81, 127.85, 128.50, 135.48, 141.99, 156.81, 158.29, 169.06, 190.04. MS (EI): m/z (%) = 362 (72) [M⁺], 334 (21), 257 (100). Anal. Calcd for C₂₂H₂₂N₂O₃: C, 72.91; H, 6.12; N, 7.73. Found: C, 72.79; H, 6.14; N, 7.70.
Compound 6m: white crystals; mp 138-139 °C; R _f = 0.68 (EtOAc). IR (KBr): 1698, 1608, 1535, 1153, 907 cm^-1. ¹H NMR (CDCl₃): δ = 0.64 (dd, J = 6.9, 24 Hz, 6 H), 1.41-1.47 (m, 1 H), 1.99-2.07 (m, 2 H), 2.54-2.60 (m, 1 H), 2.66-2.78 (m, 2 H), 3.39-3.61 (m, 3 H), 4.03-4.12 (m, 1 H), 7.31-7.37 (m, 5 H), 12.80 (s, 1 H). ¹³C NMR (CDCl₃): δ = 19.19, 20.80, 20.86, 32.83, 35.27, 37.24, 38.60, 38.64, 90.80, 127.10, 128.01, 128.41, 142.51, 156.09, 170.47, 190.60. MS (EI): m/z (%) = 298 (3) [M⁺], 255 (100), 227 (30). Anal. Calcd for C₁₈H₂₂N₂O₂: C, 72.46; H, 7.43; N, 9.39. Found: C, 72.57; H, 7.41; N, 9.42.
Compound 6n: white crystals; mp 105-106 °C; R _f = 0.55 (EtOAc). IR (KBr): 1701, 1609, 1538, 1152, 906 cm^-1. ¹H NMR (CDCl₃): δ = 0.81-0.86 (t, J = 7.2 Hz, 3 H), 0.90-1.30 (m, 12 H), 1.99-2.08 (m, 2 H), 2.54-2.62 (m, 1 H), 2.67-2.74 (m, 2 H), 3.38-3.64 (m, 3 H), 4.04-4.12 (m, 1 H), 7.31-7.38 (m, 5 H), 12.78 (s, 1 H). ¹³C NMR (CDCl₃): δ = 14.12, 20.72, 22.60, 26.71, 29.05, 29.07, 30.65, 31.72, 35.02, 37.26, 38.62, 38.71, 92.32, 126.57, 128.08, 128.32, 142.36, 155.89, 170.19, 189.92. MS (EI): m/z (%) = 354 (7) [M⁺], 326 (5), 255 (100), 227 (23). Anal. Calcd for C₂₂H₃₀N₂O₂: C, 74.54; H, 8.53; N, 7.90. Found: C, 74.42; H, 8.53; N, 7.93.

8 Zhao M.-X. Wang M.-X. Huang Z.-T. Tetrahedron 2002, 58: 1309