Molecular Diversity from Tonghaosu Analogues, Selective Reduction of the endo-Cyclic Double Bond of Tonghaosu Analogues and the Synthesis of Cyclopentenone Derivatives

Abstract

The endo-cyclic double bond of unique spiroketal dienol-ether compounds 1, 2, 3 could be selectively reduced and thus obtained products could be further converted to cyclopentenone derivatives.

spiro compound - acetals - cyclopentenone - selective hydrogenation - antifeedant

References

1 Partial result has been published in: Wu Z.-H., Wang J., Li J.-C.; X Y.-Z., Yu A.-L., Feng Z.-R., Shen J., Wu Y.-L., Guo P.-F., Wang Y.-N.; Natural Product R & D [China]; 1994, 6: 1

2a Hegnauer R. In Chemotaxonomie der Pflanzen   Vol. 3:  Birkhauser Verlag; Basel: 1964.  p.447 

2b Bohlmann F. Burkhardt T. Zdero C. Naturally Occurring Acetylenes   Academic Press; London: 1973. 

2c Greger H. In The Biology and Chemistry of Compositae   Heywood VH. Harborne JB. Turner BL. Academic Press; London: 1977.  p.Chap. 32 

2d Bohlmann F. In Chemistry and Biology of Naturally Occurring Acetylenes and Related Compounds   Lam J. Bretler H. Anason T. Hansen L. Elsvier; Amsterdam: 1988.  p.1 

2e Zdero C. Bohlmann F. Plant Syst. Evol.  1990,  171:  1 

3a Bohlmann F. Jastrow H. Ertringshausen G. Kramer D. Chem. Ber.  1964,  97:  801 

3b Bohlmann F. Florentz G. Chem. Ber.  1966,  99:  990 

4a Gao Y. Wu W.-L. Ye B. Zhou R. Wu Y.-L. Tetrahedron Lett.  1996,  37:  893 

4b Gao Y. Wu W.-L. Wu Y.-L. Ye B. Zhou R. Tetrahedron  1998,  54:  12523 

5 Fan J.-F. Zhang Y.-F. Wu Y. Wu Y.-L. Chinese J. Chem.  2001,  19:  1254 

6 Fan J.-F. Yin B.-L. Zhang Y.-F. Wu Y.-L. Wu Y. Huaxue Xuebao  2001,  59:  1756 

7 Pasto DJ. Taylor RT. In Organic Reactions   John Wiley and Sons, Inc.; Chichester: . 

8 Wade PA. Amin NV. Synth. Commun.  1982,  287 

9a Friedman L. Litle RL. Reichle WR. Org. Synth., Coll. Vol V   Wiley; New York: 1998. 

9b Cusack NJ. Reese CB. Risius AC. Roozpeikar B. Tetrahedron  1976,  32:  2157 

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Typical Procedure for Diimide Reduction: To a solution of compound 1b (0.214 g, 1 mmol) in anhyd DME (5 mL) was added TsNHNH₂ (930 mg, 5 mmol) and TMEDA (2 mL, 10 mmol). The mixture was stirred under reflux for 12 h before cooled to r.t., washed with H₂O and brine, and then dried with MgSO₄. After removal of the solvents, the residue was purified by chromatography on silica gel (eluting with 30:1 hexane-EtOAc) to give compound 4b (0.192 g, 89%). ¹H NMR (600 MHz, CD₃COCD₃): d = 7.37 (2 H, d, J = 7.2Hz), 7.12 (2 H, m), 6.90 (1 H, m), 5.06 (1 H, s), 3.87 (1 H, m), 3.80 (1 H, m), 2.77 (1 H, m), 2.60 (1 H, m), 2.13-1.92 (6 H, m). MS (abundance): m/ z (%) = 217 (34.6), [M⁺ + 1], 216(100) [M⁺], 199 (7.3), 97 (85.3). IR_max: 3056, 2987, 2891, 1673, 1596, 1493, 1448, 1362 cm^-1. Anal. Calcd for C₁₄H₁₆O₂: C, 77.75; H, 7.47. Found: C, 77.74; H, 7.67.

11a Satoh T. Nanba K. Suzuki S. Chem. Pharm. Bull.  1971,  19:  817 

11b Narisada M. Horibe I. Watanabe F. Takeda K. J. Org. Chem.  1989,  54:  5308 

11c Ren PD. Pan SF. Dong TW. Wu SH. Synth. Commun.  1959,  25:  3395 

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Typical Procedure for NaBH ₄ -NiCl ₂ Reduction: To a solution of compound 1c (0.774 g, 3 mmol) in DME (5 mL) and anhyd MeOH was added NaBH₄ (1.11 g, 30 mmol) at 0 °C, and then NiCl₂ (0.2 g, 1.5 mmol) in portions. The mixture was stirred at r.t. for 6 h until the material disappeared according to TLC. The reaction was quenched by adding sat. NaHCO₃ to pH = 8, then extracted with diethyl ether and the combined organic layers were washed with brine and dried over Na₂SO₄. Removal of solvents yielded a crude product, which was purified by chromato-graphy to afford 4c (0.702 g, 90%). ¹H NMR (300 MHz, CD₃COCD₃): d = 7.20 (1 H, d, J = 1.6 Hz), 6.85-6.68 (2 H, m), 5.90 (2 H, s), 5.12 (1 H, d, J = 1.2 Hz), 4.00-3.87 (2 H, m), 2.88 (1 H, m), 2.66 (1 H, m), 2.23-2.02 (6 H, m). MS (abundance) m/z = 261 (22.1) [M⁺ + 1], 260 (100) [M⁺], 147 (16.3), 135 (17.0), 119 (9.1), 97 (82.3). IR_max: = 2895, 1671, 1597, 1503, 1488, 1443, 1349, 1247 cm^-1. HRMS: Calcd for C₁₅H₁₆O₄: 260.1049. Found: 260.1043.

13 Fan J.-F. Wu Y. Wu Y.-L. J. Chem. Soc., Perkin Trans. 1  1999,  1189 

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Typical Procedure for Rearrangement of the Reduced Product to Cyclpentenone: To a solution of compound 4e (0.244 g, 1 mmol) in THF (5 mL) was added 2% HCl (3 mL). The reaction mixture was stirred at r.t. for 30 min until the starting material disappeared according to TLC. Then 5% NaOH was added to the mixture until pH = 13. The reaction mixture was stirred at r.t. for 4 h and then extracted with ether. The combined organic layers were washed with brine and dried over Na₂SO₄. Removal of solvents yielded a crude product, which was purified by chromatography to afford 8e (0.193 g, 80%). ¹H NMR (300 MHz, CDCl₃): d = 7.15 (2 H, d, J = 9.0 Hz), 6.90 (2 H, d, J = 9.0 Hz), 3.77 (s, 3 H), 3.56 (2 H, t, J = 4.3 Hz), 2.64 to ca. 2.55 (4 H, m), 2.48 (2 H, m), 1.76 (2 H, m). MS (m/z, abundance): 246 (M⁺, 100), 202 (72.3), 171 (61.2), 159 (92.5), 115 (45.1); IR_max: 3422, 2935, 2839, 1697, 1605, 1359, 1033, 927, 834, 754 cm^-1. Anal. Calcd for C₁₅H₁₈O₃: C, 73.17; H, 7.32. Found: C, 73.01; H, 7.54.

15 Piancatelli G. D’Auria M. D’Onofrio F. Synthesis  1994,  867