Method for Synthesizing Axial Chiral Biaryl Compounds Using Tertiary Amine Organic Small Molecules

A technology for small molecules and compounds, which is applied in the field of synthesis of axial chiral biaromatic compounds to achieve the effects of good yield, good selectivity and easy modification of substrates

Inactive Publication Date: 2018-05-08
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to overcome the shortcomings of the existing synthetic methods of axial chiral biaryl compounds, to provide a method that does not use expensive heavy metal catalysts and chiral ligands, is environmentally friendly, and the reaction is easy to operate. Easy-to-modify, high-yield, high-selectivity method for synthesizing axial chiral biaryl compounds

Method used

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  • Method for Synthesizing Axial Chiral Biaryl Compounds Using Tertiary Amine Organic Small Molecules
  • Method for Synthesizing Axial Chiral Biaryl Compounds Using Tertiary Amine Organic Small Molecules
  • Method for Synthesizing Axial Chiral Biaryl Compounds Using Tertiary Amine Organic Small Molecules

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Synthesis of Axial Chiral Biaryl Compounds Shown by Formula Ⅱ-1

[0017]

[0018] Add 110 mg (0.24 mmol) of compound Ⅰ-1, 72.6 μL (0.48 mmol) of 1,8-diazabicycloundec-7-ene (DBU) into 2 mL of tert-butanol, heat to reflux for 24 hours, and use silica gel The product was separated by column chromatography, and the eluent was a mixed solution with a volume ratio of ethyl acetate and petroleum ether of 1:60 to obtain the axial chiral biaryl compound shown in formula II-1 with a yield of 82%. The dr value is 20:80, and the structural characterization data is: 1 H NMR (400MHz, CDCl 3 )δ8.00(dd, J=16.0,8.8Hz,1H),7.91(d,J=8.4Hz,1H),7.89–7.82(m,3H),7.51–7.40(m,2H),7.36(ddd ,J=8,4.8,2.8Hz,1H),7.31–7.21(m,1H),7.20–7.13(m,4H),4.50–4.29(m,1H),1.40(d,J=12Hz,2H) ,1.31(m,1H),1.18–1.09(m,3H),0.84–0.68(m,3H),0.65(d,J=6.4Hz,2H),0.58(dd,J=8.0,4.8Hz,1H ),0.46–0.38(m,6H),0.30–0.18(m,1H),-0.05–-0.15(m,1H),-0.20(dd,J=23.3,12.0Hz,1H); 13 C NMR (100MHz, CDCl 3 )δ167.85,167.52,139.40,139...

Embodiment 2

[0022] Synthesis of Axial Chiral Biaryl Compounds Shown in Formula Ⅱ-2

[0023]

[0024] Add 180 mg (0.35 mmol) of compound Ⅰ-2 and 104 μL (0.7 mmol) of DBU into 3 mL of tert-butanol, heat to reflux for 24 hours, and separate the product by silica gel column chromatography. The eluent is the volume of ethyl acetate and petroleum ether. Mixed solution with a ratio of 1:10, the axial chiral biaryl compound shown in formula II-2 was obtained, the yield was 80%, the dr value was 27:73, and the structural characterization data was: 1 HNMR (400MHz, CDCl 3)δ7.99–7.86(m,3H),7.80(d,J=8.4Hz,1H),7.51(dd,J=16.4,8.8Hz,1H),7.40(dd,J=11.6,5.6Hz,1H ),7.35(d,J=6.8Hz,1H),7.27(d,J=7.2Hz,1H),7.25–7.20(m,2H),7.18(s 1H),6.57(s,1H),6.46( s,1H),4.42(td,J=10.8,4Hz,1H),3.99(s,3H),3.41(d,J=23.6Hz,3H),1.39(m,4H),1.20–1.12(m, 1H),0.88(m,1H),0.81–0.72(m,1H),0.70(d,J=6.4Hz,2H),0.63(d,J=6Hz,1H),0.55–0.43(m,6H) ,0.29(t,J=9.6Hz,1H),0.05–-0.02(m,1H),-0.05(s,1H),-0.21(dd,J=23.2,12.0Hz,1H); 13 C NMR (100M...

Embodiment 3

[0028] Synthesis of Axial Chiral Biaryl Compounds Shown by Formula Ⅱ-3

[0029]

[0030] Add 100 mg (0.24 mmol) of compound Ⅰ-3 and 108 μL (0.72 mmol) of DBU into 2 mL of tert-butanol, heat to reflux for 12 hours, and separate the product by silica gel column chromatography. The eluent is the volume of ethyl acetate and petroleum ether. The mixed solution with a ratio of 1:100 can obtain the axial chiral biaryl compound shown in formula II-3, the yield is 83%, the dr value is 18:82, and the structural characterization data are: 1 H NMR (400MHz, CDCl 3 )δ8.01(dd, J=19.2,8.0Hz,1H),7.93(d,J=9.2Hz,2H),7.58–7.53(m,1H),7.37(m,4H),7.27(m,1H ),7.11(dd,J=18.4,7.6Hz,1H),4.73(dtd,J=15.2,10.8,4.4Hz,1H),1.98(d,J=14.4Hz,3H),1.78–1.70(m, 2H),1.62(m,2H),1.38(m,1H),1.13–0.93(m,2H),0.89–0.67(m,11H),0.46(dd,J=23.6,12Hz,1H); 13 C NMR (100MHz, CDCl 3 )δ167.93,140.58,138.95,138.86,137.02,136.64,134.78,134.62,132.45,132.25,129.63,129.42,129.34,128.77,127.95,127.87,127.55,127.52,127.41,127.37,...

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Abstract

The invention discloses a method for synthesizing axial chiral biaryl compounds by utilizing tertiary amine small organic molecules. According to the method, similar Mortia-Baylis-Hillman reactions in molecules are utilized, and chiral prosthetic groups are used as inducing groups, so that axial chiral biaryl compounds are asymmetrically constructed in one step. The method for synthesizing the axial chiral biaryl compounds has the advantages of environmental friendliness, no use of expensive metal catalysts, atom economy and easiness in modification of substrates, the yield of the biaryl compounds as products can reach 80% to 97%, and a De value reaches 70% to 80%. The invention provides a green environment-friendly way for various preparations of the axial chiral biaryl compounds.

Description

technical field [0001] The invention belongs to the technical field of synthesizing axial chiral biaryl hydrocarbon compounds, and specifically relates to a kind of chiral prosthetic group as an inducing group, under the action of a tertiary amine organic small molecule, through a similar Mortia-Baylis-Hillman reaction in the molecule , to achieve a one-step asymmetric construction of biaryl compounds with axial chirality. Background technique [0002] In the past two decades, many naturally occurring axial chiral biaryl compounds have attracted widespread attention from researchers due to their good pharmacological activities, such as Korupensamine A and Korupensamine A. Korupensamine B (Korupensamine B, the axial chiral isomer of Korupensamine A) all showed very significant antimalarial activity, while Korupensamine A and Korupensamine Michellamine B, a dimer of phytogenine B, has strong antiviral activity against HIV-1 and HIV-2 viruses (Xu, G.; Fu, W.Z.; Liu, G.; Senana...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C67/30C07C69/76C07C69/94
CPCC07C67/30C07C69/76C07C69/94
Inventor 柴永海赵贝贝康磊周瑾瑾张琦
Owner SHAANXI NORMAL UNIV
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