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Alpha-fluoroalkyl substituted cyclopropyl alcohol compound as well as preparation method and application thereof

A fluoroalkyl and cyclopropyl technology, applied in the field of organic synthesis, can solve the problem of uncontrollable substrate regioselectivity, and achieve good substrate universality, good functional group tolerance, and good diastereoselectivity. Effect

Pending Publication Date: 2022-05-10
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods cannot control the substrate regioselectivity, and require multi-step synthesis for specific aldehydes or ketones, so it is urgent to develop a method that can directly introduce α-fluoroalkyl alcohol cleavage

Method used

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  • Alpha-fluoroalkyl substituted cyclopropyl alcohol compound as well as preparation method and application thereof
  • Alpha-fluoroalkyl substituted cyclopropyl alcohol compound as well as preparation method and application thereof
  • Alpha-fluoroalkyl substituted cyclopropyl alcohol compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032]

[0033] In a glove box, A (38.8 mg, 0.2 mmol), dried DCE (0.5 mL) and B (92.8 mg, 0.4 mmol, 2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stir bar. The photoreaction tube was sealed, taken out from the glove box, and then irradiated with a 6W blue LED lamp, and the reaction mixture was stirred at room temperature for 24 hours. Then the blue light was turned off, TBAF (0.24 mL, 1.0 M in THF, 1.2 equiv.) was added, and the mixture was stirred under ice bath for 10 min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh), and eluted with PE / EA (20 / 1-10 / 1, v / v) to obtain the target compound G1 (52.6 mg of colorless oily liquid, yield 90% ). 1 H NMR (400MHz, CDCl 3 ,25℃)δ7.57(dd,J=1.8,0.9Hz,1H),7.18(dd,J=3.5,0.9Hz,1H),6.51(dd,J=3.5,1.7Hz,1H),4.49– 4.21(m,2H),2.97(s,1H),1.88–1.77(m,2H),1.61–1.48(m,4H),1.26–1.15(m,2H),0.69–0.58(m,1H). 13 C NMR (151MH...

Embodiment 2

[0035]

[0036] In a glove box, A (20.8 mg, 0.2 mmol), dry DCM (0.5 mL) and B (92.8 mg, 0.4 mmol, 2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stir bar. The photoreaction tube was sealed, taken out from the glove box, and then irradiated with a 6W blue LED lamp, and the reaction mixture was stirred at room temperature for 24 hours. Then the blue light was turned off, TBAF (0.24 mL, 1.0 M in THF, 1.2 equiv.) was added, and the mixture was stirred under ice bath for 10 min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh), and eluted with PE / EA (50 / 1-10 / 1, v / v) to obtain the target compound G2 (colorless oily liquid 28.3mg, yield 70% ). 1 H NMR (600MHz, CDCl 3 , 25°C) δ7.38-7.31(m, 2H), 7.31-7.27(m, 1H), 7.25-7.21(m, 2H), 2.58(dd, J=10.4, 7.8Hz, 1H), 2.46(s , 1H), 1.57(dd, J=10.5, 6.9Hz, 1H), 1.48-1.39(m, 1H). 19 F NMR (375MHz, CDCl 3 , 25°C) δ77.1...

Embodiment 3

[0038]

[0039] In a glove box, A (20.8 mg, 0.2 mmol), dry DCM (0.5 mL) and B (92.8 mg, 0.4 mmol, 2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stir bar. The photoreaction tube was sealed, taken out from the glove box, and then irradiated with a 6W white LED lamp, and the reaction mixture was stirred at room temperature for 24 hours. Then the blue light was turned off, TBAF (0.24 mL, 1.0 M in THF, 1.2 equiv.) was added, and the mixture was stirred under ice bath for 10 min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh), and eluted with PE / EA (50 / 1-10 / 1, v / v) to obtain the target compound G3 (colorless oily liquid 27.2mg, yield 67% ). 1 H NMR (600MHz, CDCl 3 , 25°C) δ7.38-7.31(m, 2H), 7.31-7.27(m, 1H), 7.25-7.21(m, 2H), 2.58(dd, J=10.4, 7.8Hz, 1H), 2.46(s , 1H), 1.57(dd, J=10.5, 6.9Hz, 1H), 1.48-1.39(m, 1H). 19 F NMR (375MHz, CDCl 3 , 25°C) δ77....

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Abstract

The invention relates to the technical field of organic synthesis, in particular to an alpha-fluoroalkyl substituted cyclopropyl alcohol compound as well as a preparation method and application thereof, the molecular structural formula of the alpha-fluoroalkyl substituted cyclopropyl alcohol compound is shown in the specification, R1, R2, R3 and R4 are respectively any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitryl, sulfonyl, heteroatom and hydrogen atom, Rf is CF3, CF2R5 or CFR6R7, Rf is CF3, CF2R5 or CFR6R7, and R1, R2, R3 and R4 are respectively any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitryl, sulfonyl, heteroatom and hydrogen atom. R5 is any one of halogen, aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitryl, sulfonyl, carboxyl, heteroatom and hydrogen atom; r6 and R7 are respectively any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitryl, sulfonyl, heteroatom and hydrogen atom, and can be the same or different. The alpha-fluoroalkyl substituted cyclopropyl alcohol compound disclosed by the invention is a novel compound structure and has high diastereoselectivity.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to an α-fluoroalkyl substituted cyclopropyl alcohol compound, a preparation method and application thereof. Background technique [0002] α-Fluoroalkyl alcohol cleavages are widely found in many bioactive compounds, thus attracting the attention of synthetic organic chemists. However, the method for directly synthesizing α-fluoroalkyl alcohols is limited. In 2012, Reissig et al. reported the synthesis of fluoroalkyl-substituted cyclopropenyl ethers [H.-U.Reissig, Helvetica Chimica Acta, 2012,95( 10), 1818-1830], under the catalysis of transition metal rhodium acetate, the cyclization reaction of fluorine-containing enol silicon ether and diazo compound [2+1] obtained α-fluoroalkyl cyclopropyl silicon ether, the reaction It can't control dr very well, and the low content is limited to diazo compounds containing ester groups, and the substrate universality is poor. The tra...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/68C07C35/04C07C29/40C07D333/40C07D231/12C07C45/00C07C49/233C07C255/57C07C253/30C07C69/78C07C67/29C07C69/76C07C69/16C07C49/173C07C45/69C07C43/23C07C41/30
CPCC07D307/68C07C35/04C07D333/40C07D231/12C07C45/00C07C255/57C07C69/78C07C69/76C07C69/16C07C49/173C07C43/23C07C49/233
Inventor 沈晓周刚
Owner WUHAN UNIV
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