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Preparation method of chiral Beta-indolyl-Gamma-aldehyde group nitro alkanes

An aldehyde nitroalkane and indolyl technology, applied in the field of asymmetric catalysis, can solve the problems of unreported and limited indole-derived nitroalkenes, and achieve the simple and easy-to-obtain substrate raw materials, high compatibility, and application. wide range of effects

Inactive Publication Date: 2012-12-26
SUZHOU UNIV
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  • Abstract
  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

[0003] β-indolyl-γ-aldehyde nitroalkanes belong to the 3-position derivatives of indole, but the stereoselective construction of β-indolyl-γ-aldehyde nitroalkanes by Michael addition has not been reported yet
[0004] Although the asymmetric Michael addition reaction of nitroalkenes is well established, nitroalkenes are mainly limited to aryl (substituted phenyl, heterocyclic) nitroalkenes, other types of nitroalkenes are rarely reported, and indole-derived Nitroenes have not been reported
However, the asymmetric Friedel-Crafts reaction of indole with α, β unsaturated aldehydes and nitroalkenes can only construct a chiral center

Method used

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  • Preparation method of chiral Beta-indolyl-Gamma-aldehyde group nitro alkanes
  • Preparation method of chiral Beta-indolyl-Gamma-aldehyde group nitro alkanes
  • Preparation method of chiral Beta-indolyl-Gamma-aldehyde group nitro alkanes

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027]

[0028] (S)-diphenylprolinol trimethylsilyl ether (6.51 mg, 0.02 mmol) and 2a (37.6 mg, 0.2 mmol) were successively charged into the reaction flask, 1 mL of dichloromethane was added, and stirred at room temperature for 10 min , then added 1a (72 mg, 1 mmol), and the reaction was monitored by thin-layer chromatography until the reaction was completed. After 40 hours, the solvent was removed, and the crude product was subjected to simple column chromatography (eluent: ethyl acetate:petroleum ether=1:5 ) to obtain the target product, light yellow oil 3a (50.0 mg), with a yield of 96%.

[0029] The product was analyzed and the results were as follows: 96% yield, 98% ee, dr = 81 / 19. HPLC: Chiralcel OD-H, hexane / i-PrOH = 80:20, flow rate: 1.0 mL min -1 , λ = 210 nm, t major = 25.731 min, t minor = 20.987 min; [α] D 25 = -2.08 (c 2.16, CH 3 COCH 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 9.70 (d, J = 2.4 Hz, 1H), 8.29 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.36-7.29 (m, 1H...

Embodiment 2

[0031]

[0032] (S)-Diphenylprolinol trimethylsilyl ether (6.5 mg, 0.02 mmol) and 2b (40.5 mg, 0.2 mmol) were successively charged into the reaction flask, 1 mL of dichloromethane was added, and stirred at room temperature for 10 min , then added 1a (72 mg, 1 mmol), and the reaction was monitored by thin-layer chromatography until the reaction was completed. After 72 hours, the solvent was removed, and the crude product was subjected to simple column chromatography (eluent: ethyl acetate:petroleum ether=1:5 ) to obtain the target product, light yellow oil 3b (43.9 mg), with a yield of 80%.

[0033] The product was analyzed and the results were as follows: 80% yield, 96% ee, dr = 93 / 7. HPLC: Chiralcel OD-H, hexane / i-PrOH = 80:20, flow rate: 1.0 mL min -1 , λ = 210 nm, t major = 27.079 min, t minor = 20.001 min; [α] D 25 = -6.30 (c 1.84, CH 3 COCH 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 9.72 (d, J = 2.4 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.31-7.22 (m, 2H), 7.17-7.11 (m,...

Embodiment 3

[0035]

[0036] (S)-diphenylprolinol trimethylsilyl ether (6.5 mg, 0.02 mmol) and 2c (65.7 mg, 0.2 mmol) were successively charged into the reaction flask, 1 mL of dichloromethane was added, and stirred at room temperature for 10 min , then added 1a (72 mg, 1 mmol), and the reaction was monitored by thin-layer chromatography until the reaction was completed. After 0.5 h, the solvent was removed, and the crude product was subjected to simple column chromatography (eluent: ethyl acetate:petroleum ether=1: 5) The target product, light yellow oil 3c (73.7 mg), was obtained with a yield of 92%.

[0037] The product was analyzed and the results were as follows: 92% yield, 99% ee, dr = 91 / 9. HPLC: Chiralcel OD-H, hexane / i-PrOH (80:20) , flow rate: 1.0 mL·min -1 , λ = 254 nm, t major = 41.177 min, t minor = 34.343 min; [α] D 25 = -3.52 (c 1.90, CH 3 COCH 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 9.72 (d, J = 1.6 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 7.6 Hz, 2H), 7.56-...

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Abstract

The invention discloses a preparation method of chiral Beta-indolyl-Gamma-aldehyde group nitro alkanes. According to the method, (S)-diphenyl prolinol trimethylsilyl ether is used as a catalyst, methylene chloride is used as a solvent, and indol 3-position derived nitroolefin and aliphatic aldehyde are used as reactants to react under -30 DEG C to room temperature for 0.5 to 72 hours to obtain the chiral Beta-indolyl-Gamma-aldehyde group nitro alkanes. The invention achieves the synthesis method of synthetizing chiral Beta-indolyl-Gamma- aldehyde group nitro alkanes from indol 3-position derived nitroolefin and aliphatic aldehyde with L-proline derivative chiral secondary amine as a catalyst for the first time, which has higher yield and stereoselectivity.

Description

technical field [0001] The invention belongs to the field of asymmetric catalysis, and in particular relates to a method for preparing chiral β-indolyl-γ-aldehyde nitroalkane by catalyzing a chiral secondary amine catalyst. Background technique [0002] Organocatalyzed Michael addition reaction is an efficient synthetic method for the synthesis of multifunctional compounds with continuous chiral centers, and the 3-position derivatives of indole are the core fragments of many natural products and modern drugs. [(a) O. M. Berner, L. Tedeschi, D. Enders, Eur. J. Org. Chem., 2002, 1877–1894; (b) S. B. Tsogoeva, Eur. J. Org. Chem., 2007, 1701–1716 ; (c) A. C. Kinsman, M. A. Kerr, Org. Lett., 2001, 3, 3189–3191; (d) D. King, Z. Meng, D. Denhart, R. Mattson, R. Kimura, D. Wu, Q. Gao, J. E. Macor, Org. Lett., 2005, 7, 3437–3440; (e) S. Hanessian, E. Stoffman, X. Mi, P. Renton, Org. Lett., 2011, 13, 840– 843; (f) X. Zhang, T. Mu, F. Zhan, L. Ma, G. Liang, Angew. Chem., Int. Ed., 20...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12
Inventor 王兴旺陈坚
Owner SUZHOU UNIV
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