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Chiral gamma-butyrolactone and preparation by asymmetric allylic alkylation reaction catalysed by chiral phosphonic compound

A compound, butyrolactone technology, applied in the direction of organic compound/hydride/coordination complex catalyst, asymmetric synthesis, organic chemical method, etc., can solve the problems of polluted products, high price, high toxicity, etc.

Inactive Publication Date: 2008-08-27
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, metal-organic catalysts usually have disadvantages such as high price, high toxicity, easy pollution to the environment, and metal compounds will pollute products. This has always been a difficulty for people to break through.

Method used

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  • Chiral gamma-butyrolactone and preparation by asymmetric allylic alkylation reaction catalysed by chiral phosphonic compound
  • Chiral gamma-butyrolactone and preparation by asymmetric allylic alkylation reaction catalysed by chiral phosphonic compound
  • Chiral gamma-butyrolactone and preparation by asymmetric allylic alkylation reaction catalysed by chiral phosphonic compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Add substrate (1-1a; 27mg, 0.125mmol) and catalyst L7 (7mg, 0.0125mmol) to the reaction tube at room temperature, ventilate, then add toluene (0.4mL), water (6% of the amount of substrate) equivalent, 13.5 μL) and 2-trimethylsilylfuran (51 μL, 0.32 mmol). Continue stirring at room temperature for 40h to terminate the reaction, remove the solvent by rotary evaporation, and separate with flash column chromatography (SiO 2 , the eluent was ethyl acetate / petroleum ether=1 / 5), to obtain compound 1-3a (28 mg, 94%); white oil. [α] D 20 -31.7 (c 0.65, CHCl 3 ); 1 H NMR (300MHz, CDCl 3 , TMS) δ2.32 (3H, s, Me), 4.40 (1H, d, J=7.2Hz), 5.56 (1H, ddd, J=7.2, 3.3, 1.5Hz), 6.06-6.08 (1H, m) , 6.09(1H, s), 6.36(1H, s) 7.28-7.36(6H, m); HPLC: OD column; λ=230nm; elution: n-hexane / isopropanol=80 / 20; flow rate: 0.7mL / min;t minor = 16.24min, t major = 22.58 min; ee% = 94%.

Embodiment 2

[0062] Add substrate (1-1b; 29mg, 0.125mmol) and catalyst L7 (7mg, 0.0125mmol) to the reaction tube at room temperature, ventilate, then add toluene (0.4mL), water (6% of the amount of substrate) equivalent, 13.5 μL) and 2-trimethylsilylfuran (51 μL, 0.32 mmol). Continue stirring at room temperature for 36h to terminate the reaction, remove the solvent by rotary evaporation, and separate with flash column chromatography (SiO 2 , the eluent was ethyl acetate / petroleum ether=1 / 5) to obtain compound 1-3b (30 mg, 94%); white oil. [α] D 20 -49.9 (c 1.25, CHCl 3 ); IR (KBr): ν2958, 2932, 2873, 1791, 1766, 1514, 1364, 1161, 1100, 1037, 898, 814, 735, 547cm -1 ; 1 H NMR (CDCl 3 , TMS, 300MHz) δ2.29 (3H, s, Me), 2.32 (3H, s, Me), 4.32 (1H, d, J=7.5Hz), 5.52 (1H, ddd, J=7.2, 3.6, 1.8 Hz), 6.03-6.05(1H, m), 6.06(1H, s), 6.32(1H, s), 7.13(2H, d, J=7.8Hz), 7.22(2H, d, J=7.8Hz), 7.27 (1H, dd, J=5.7, 1.5Hz); 13 C NMR (CDCl 3 , TMS, 75.44MHz): δ21.0, 25.8, 47.0, 83.5, 121.6, 128.2, ...

Embodiment 3

[0064]Add substrate (1-1d; 37mg, 0.125mmol) and catalyst L7 (7mg, 0.0125mmol) to the reaction tube at room temperature, ventilate, then add toluene (0.4mL), water (6% of the amount of substrate) equivalent, 13.5 μL) and 2-trimethylsilylfuran (51 μL, 0.32 mmol). Continue stirring at room temperature for 24h to terminate the reaction, remove the solvent by rotary evaporation, and separate with flash column chromatography (SiO 2 , the eluent was ethyl acetate / petroleum ether=1 / 5) to obtain compound 1-3d (34 mg, 85%); white solid. [α] D 20 -14.6 (c 1.75, CHCl 3 ); mp: 96-99°C; IR (KBr): ν3096, 2956, 2925, 2854, 1790, 1765, 1677, 1629, 1601, 1489, 1406, 1365, 1296, 1225, 1160, 1130, 1100, 1075, 1038, 1011, 982, 898, 814, 543cm -1 ; 1 H NMR (CDCl 3 , TMS, 300MHz) δ2.31 (3H, s, Me), 4.40 (1H, d, J=6.6Hz), 5.52 (1H, ddd, J=6.3, 3.3, 1.5Hz), 6.03 (1H, s) , 6.07(1H,dd,J=6.0,1.5Hz), 6.36(1H,s), 7.24(2H,d,J=8.4Hz), 7.26-7.30(1H,m), 7.46(2H,d,J = 8.4Hz); 13 CNMR (CDCl 3 , TMS, 7...

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Abstract

The invention relates to a compound provided with a gamma-butyrolactone annular structure with high asymmetry selectivity and a relative synthesis method. The synthesis method uses chiral phosphine as catalyst, adds water into reaction as additive, and uses compound 1-1 and compound 1-2 in the presence of the catalyst to synthesize chiral gamma-butyrolactone compound. The invention has high yield and high ee value of product and the invention can obtain the compound with chiral gamma-butyrolactone annular structure with high enantio-selectivity, therefore the invention can prepare key chiral intermediate of chiral drug synthesis.

Description

technical field [0001] The invention relates to a method for constructing a chiral gamma-butyrolactone ring-structured compound through the asymmetric catalyzed allyl alkylation reaction of small molecules and the compound obtained by the method. Background technique [0002] Chirality is an inherent universal feature of matter at different levels (Gardner, M. The New Ambidextrous Universe, 3 rd ed., Freeman, W.H. & Co., New York, 1990). Chiral molecules play an important role in science and technology, especially in life activities, because many physiological functions are asymmetric. Many physiological phenomena originate from the precise recognition and strict matching of molecular chirality, and the chiral biological receptor interacts with the two enantiomers of the guest in different ways. Finding truly efficient ways to obtain optically pure products is a major challenge for both industrial and academic chemists. Generally, there are several methods for the synthe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/58C07B53/00B01J31/02
Inventor 姜迎庆施敏
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI