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Method for synthesizing tetrahydroquinoline compounds by taking inert cyclopropane as raw material

A technology of tetrahydroquinoline and cyclopropane, applied in the application field, can solve the problems of limited reaction type of inert cyclopropane, poor functional group tolerance, single reaction type, etc., and achieves good catalytic effect, simple operation and wide range of substrates. Effect

Inactive Publication Date: 2020-09-18
NANKAI UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with the activated cyclopropanes introduced in the previous two sections, different types of cycloaddition reactions can occur. The reaction types of inert cyclopropanes are limited, and there are few research reports. The types of reactions involved are single, the reaction substrates are limited, and the functional group tolerance is relatively low Difference

Method used

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  • Method for synthesizing tetrahydroquinoline compounds by taking inert cyclopropane as raw material
  • Method for synthesizing tetrahydroquinoline compounds by taking inert cyclopropane as raw material
  • Method for synthesizing tetrahydroquinoline compounds by taking inert cyclopropane as raw material

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Synthesis of 7b-(4-methoxyphenyl)-3-methyl-1a, 2,3,7b-tetrahydro-1H-cyclopropa[c]Quinoline

[0026]

[0027] Under nitrogen atmosphere, in the reaction bottle of 15mL, raw material 1a (26.7mg, 0.1mmol), B(C 6 f 5 ) 3 (10.24mg, 0.02mmol), dissolved in dry toluene (1mL), then added BTMG (3.42mg, 0.02mmol), TMSOTf (4.44mg, 0.02mmol) and reacted at 150°C for 24 hours. After the reaction was completed, it was separated by silica gel column chromatography, and the eluent was (petroleum ether / ethyl acetate=100 / 1) to obtain 17.2 mg of product 2a (white solid), with a yield of 65%. 1 H NMR (400MHz, CDCl 3 ( s, 3H), 3.35(d, J=10.4Hz, 1H), 3.25(d, J=10.4Hz, 1H), 2.85(s, 3H), 1.81-1.80(m, 1H), 1.72-1.69(m , 1H), 1.32-1.29(m, 1H); 13 C NMR (101MHz, CDCl 3 )δ158.4, 144.5, 136.9, 131.9, 130.3, 128.5, 126.1, 117.7, 113.8, 111.3, 77.48, 55.4, 48.5, 39.2, 27.9, 27.1, 13.8. HRMS (ESI) m / z calcd for C 18 h 20 NO + (M+H) + 266.1539, found 266.1542.

Embodiment 2

[0028] Example 2: Synthesis of 2-(1-(4-methoxyphenyl)cyclopropyl)-N,N,5-trimethylaniline

[0029]

[0030] Under nitrogen atmosphere, in the reaction bottle of 15mL, raw material 1b (28.1mg, 0.1mmol), B(C 6 f 5 ) 3 (10.24mg, 0.02mmol), dissolved in dry toluene (1mL), then added BTMG (3.42mg, 0.02mmol), TMSOTf (4.44mg, 0.02mmol) and reacted at 150°C for 24 hours. After the reaction was completed, the product was separated by silica gel column chromatography, and the eluent was (petroleum ether / ethyl acetate=100 / 1) to obtain 15.6 mg of product 2b (white solid), with a yield of 56%. 1 H NMR (400MHz, CDCl 3 )δ7.29(d, J=8.2Hz, 1H), 6.98(d, J=8.6Hz, 2H), 6.82-6.81(m, 2H), 6.74(d, J=8.6Hz, 2H), 3.75( s, 3H), 2.60 (s, 6H), 2.33 (s, 3H), 1.41-1.38 (m, 2H), 1.28-1.25 (m, 2H); 13 C NMR (101MHz, CDCl 3 )δ157.1, 153.4, 139.8, 137.2, 134.3, 133.4, 126.8, 122.7, 120.1, 113.4, 55.4, 44.4, 26.36, 21.5, 19.3. HRMS (ESI) m / z calcd for C 19 h 24 NO + (M+H) + 282.1852, found 282.1859....

Embodiment 3

[0031] Example 3: Synthesis of 7b-(4-(benzyloxy)phenyl)-3-methyl-1a, 2,3,7b-tetrahydro-1H-cyclopropa[c]Quinolone

[0032]

[0033] Under a nitrogen atmosphere, in a 15mL reaction flask, the raw material 1c (34.3mg, 0.1mmol), B(C 6 f5 ) 3 (10.24mg, 0.02mmol), dissolved in dry toluene (1mL), then added BTMG (3.42mg, 0.02mmol), TMSOTf (4.44mg, 0.02mmol) and reacted at 150°C for 24 hours. After the reaction was completed, it was separated by silica gel column chromatography, and the eluent was (petroleum ether / ethyl acetate=100 / 1) to obtain 21 mg of product 2c (white solid), with a yield of 62%. 1 H NMR (400MHz, CDCl 3 )δ7.51-7.49 (m, 2H), 7.43-7.40 (m, 2H), 7.40-7.36 (m, 3H), 7.12-7.08 (m, 1H), 7.02-7.0 (m, 2H), 6.74- 6.72(m, 1H), 6.68-6.62(m, 3H), 5.12(s, 2H), 3.39(d, J=11.5Hz, 1H), 3.29(d, J=11.5Hz, 1H), 2.89(s , 3H), 1.88-1.84(m, 1H), 1.77-1.75(m, 1H), 1.37-1.34(m, 1H); 13 C NMR (101MHz, CDCl 3 ) 157.6, 144.5, 137.2, 131.9, 130.2, 128.8, 128.5, 128.1, 127.7, 126.1, 11...

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Abstract

The invention provides a method for efficiently synthesizing tetrahydroquinoline compounds from inert cyclopropane under the catalysis of boron Lewis acid, belonging to the field of application technology. The method is characterized in that an intramolecular ring expansion reaction of inert cyclopropane is realized, cyclopropane and imine positive ions firstly form a seven-membered ring intermediate, and then BTMG (2-tert-butyl-1,1,3,3-tetramethylguanidine) is used for attacking beta-position protons to generate a nitrogen-containing heterocyclic compound.

Description

technical field [0001] The invention provides a method for efficiently synthesizing tetrahydroquinoline compounds from inert cyclopropane under the catalysis of boro-Lewis acid, which belongs to the field of application technology. Background technique [0002] Cyclopropane as an important C in organic chemistry 3 Synthon, its ring-opening reaction has been a research hotspot. However, due to the low degree of polarization of the C-C bond, the energy barrier required for its breakage is relatively high. In order to reduce the activation energy of the reaction, various reaction strategies have been developed. [0003] a) Introduce electron-withdrawing groups and electron-donating groups into the cyclopropane structure to construct Donor-Acceptor cyclopropane, increase the degree of C-C bond polarization through "pull-push action", and use Lewis acid to realize its ring-opening reaction. [0004] b) Introduce weakly activated groups on cyclopropane, such as alkenyl, carbonyl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/16
CPCC07D221/16
Inventor 王晓晨张子玉
Owner NANKAI UNIV
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