Compound containing framework of chiral indolone and angelica lactone and asymmetric synthesis method

An angelica lactone and product technology, applied in the field of allyl alkylated compounds, can solve problems such as the limitation of reactant types, and achieve the effects of wide application range of substrates, good yield and mild reaction conditions

Inactive Publication Date: 2012-07-18
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[(a) J. Peng, X. Huang, H.-L. Cui and Y.-C. Chen, Org. Lett., 2010, 12, 4260; (b) J. Peng, X. Huang, L. Jiang, H.-L.

Method used

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  • Compound containing framework of chiral indolone and angelica lactone and asymmetric synthesis method
  • Compound containing framework of chiral indolone and angelica lactone and asymmetric synthesis method
  • Compound containing framework of chiral indolone and angelica lactone and asymmetric synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1: Allyl alkylation of indolinone MBH carbonate and various angelica lactone compounds catalyzed by chiral cinchona base-derived b-ICD derivatives

[0021] In a clean reaction tube, add chiral cinchona base-derived b-ICD derivative catalyst (0.01 mmol), indolinone MBH carbonate (0.10 mmol), angelica lactone compound (0.20 mmol), and Mesitylene 0.1 mL, at -10 o C for the corresponding time with stirring. The product was isolated by column chromatography.

[0022]

[0023] P1, 80% yield; [α] D 20 = +8.5 ( c = 0.4 in CHCl 3 ); 90% ee, chiral test conditions: determined by HPLC analysis [Daicel Chiralcel OD, n -Hexane / i -PrOH = 80 / 20, 1.0 mL / min, λ = 254 nm, t (major) = 26.532 min, t (minor) = 18.793 min,]; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.26 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 7.2 Hz, 1H), 7.06 (d, J = 5.6 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 6.84 (s, 1H), 6.79 (d, J = 7.6 Hz, 1H), 6.75 (s, 1H), 5.70 (d, J = 5.6 Hz, 1H), 3.62 (s, 3H), 3.29 (s,...

Embodiment 2

[0037] Example 2: Transformation with multifunctional functional groups (application example 1)

[0038]

[0039] P1 (65.4 mg, 0.20 mmol) and BnNH 2 (110 μL, 1.00 mmol) dissolved in CF 3 CH 2 OH (0.5 mL), 80 o C was stirred until P1 was detected by TLC and disappeared. Add Boc at room temperature 2 O (436 mg, 2.00 mmol) to remove unreacted BnNH 2 . Column chromatography (petroleum ether / ethyl acetate: 2 / 1) gave the title compound as a colorless oil. (61.0 mg, 70% yield). [α] D 20 = -9.2 ( c = 0.9 in CHCl 3 ); 90% ee, chiral test conditions: determined by HPLC analysis [Daicel Chiralcel AD, n -Hexane / i -PrOH = 70 / 30, 1.0 mL / min, λ = 254 nm, t (major) = 15.195 min, t (minor) = 14.046 min]; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.54 (d, J = 7.2 Hz, 1H), 7.41-7.30 (m, 6H), 6.97 (td, J = 7.6 Hz, 0.8 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 3.97 (d, J = 13.6 Hz, 1H), 3.71 (dd, J = 7.2 Hz, 6.0 Hz, 1H), 3.66 (d, J = 13.6 Hz, 1H), 3.35 (d, J = 5.6 Hz, 1H), 3.29 (d...

Embodiment 3

[0040] Example 3: Transformation with multifunctional functional groups (application example 2)

[0041]

[0042] P1 (50.0 mg, 0.15 mmol), MeNO 2 (1.50 mmol, 80 μL) and DBU (0.07 mmol, 11.4 mg) in CH 3 CN (0.5 mL), 70 o C was stirred until P1 was no longer converted as detected by thin layer chromatography. Column chromatography (petroleum ether / ethyl acetate: 2 / 1) gave a white solid. (23.0 mg, 40% yield). [α] D 20 = +5.5 ( c = 0.9 in CHCl 3 ); 90% ee, chiral test conditions: determined by HPLC analysis [Daicel Chiralcel OD, n -Hexane / i -PrOH = 60 / 40, 1.0 mL / min, λ = 254 nm, t (major) = 26.963 min, t (minor) = 19.554 min]; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.42 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 4.76 (m, 1H), 3.56 (dd, J = 12.8 Hz, 5.6 Hz, 1H), 3.46 (s, 3H), 3.29 (s, 3H), 3.11 (dd, J = 10.8 Hz, 6.8 Hz, 1H), 2.86-2.80 (m, 2H), 2.97 (dd, J = 18.0 Hz, 6.8 Hz, 1H), 2.70 (d, J = 18.0 Hz, ...

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Abstract

The invention provides a high-efficiency synthesis method of a compound containing a chiral indolone and angelica lactone framework, which is an effective method of synthetizing a series of allyl alkylate chiral product with multifunction functional groups in high-efficiency high- enantioselectivity mode through indolone MBH (Morit-Baylis-Hill1man) carbonic ester and various angelica lactone compounds with chiral amines, especially derivatives of b-1CD ((3 S, 8R, 9S) -10, 11- dihydro -3,9 epoxy-6'- oxhydryl quinine alkyl) derived by cinchona alkaloid as catalysts, with 4 molecular sieve and R-BINOL as additives. The asymmetric synthesis method is reported for the first time, the catalysts are easy to obtain and high in catalytic activity, the asymmetric synthesis method is mild in reaction conditions, simple in operation, wide in substrate application range and high in product area and enantioselectivity. In addition, various obtained compounds containing the framework of indolone and angelica lactone can possibly have special physiological activity or become important synthesis intermediates of natural product.

Description

technical field [0001] The invention relates to a kind of allylic alkylation compound with multifunctional functional group synthesized by chiral amine catalyzed indolinone MBH (Morit-Baylis-Hillman) carbonate and various angelica lactone compounds, the multifunctional functional group product It may have special physiological activity or become an important synthetic intermediate of natural products. Background technique [0002] Indolinone and angelica lactone skeletons, especially the optically pure ones, widely exist in natural products and pharmaceutical intermediates. In view of the important role of these compounds in medicine, more and more chemical home interest. [(a) X. Z. Wearing and J. M. Cook, Org. Lett., 2002, 4, 4237; (b) B. K. Albrecht and R. M. Williams, Org. Lett., 2003, 5, 197; (c) S. E. Reisman, J. M. Ready, M. M. Weiss, A. Hasuoka, M. Hirata, K. Tamaki, T. V. Ovaska, C. J. Smith and J. L. Wood, J. Am. Chem. Soc., 2008, 130, 2087; (d) K. C. Nicolaou, P....

Claims

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Application Information

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IPC IPC(8): C07D405/04C07D491/20C07D491/107C07D487/10
Inventor 陈应春黄鑫蕫琳
Owner SICHUAN UNIV
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