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Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, preparation method and application thereof

A high-allylamine, multi-substitution technology, applied in the field of chemical medicine

Inactive Publication Date: 2021-01-29
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, there is no report on the synthesis of chiral α-polysubstituted-α-fluorinated homoallylamines from fluorinated fluorenimines using asymmetric catalytic allylation.

Method used

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  • Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, preparation method and application thereof
  • Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, preparation method and application thereof
  • Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] 1) preparation of

[0067] Add 0.005mmol[Ir(COD)Cl] to 25mL reaction tube 2 , 0.010mmol (S, S, S)-L1, 0.5mL deoxygenated THF and 0.5mL deoxygenated n-propylamine, reacted at 50°C for 30 minutes, and evaporated the solvent under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25°C, add 2mL of toluene, and then add 0.20mmol N-2,2,2-trifluoroethylfluorenone imine, 0.22mmol cinnamyl methyl carbonate and 0.20mmol 1,8-diazabis Cycloundec-7-ene, react at 25°C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to obtain the product.

[0068] 2) preparation of

[0069] Dissolve the product obtained in step 1) in 1 mL of dichloroethane, add a methanol solution of hydroxylamine acetate (0.5M, 1 mL, prepared in methanol from hydroxylamine hydrochloride, sodium hydroxide and ac...

Embodiment 2

[0071] 1) preparation of

[0072] Add 0.005mmol[Ir(COD)Cl] to 25mL reaction tube 2 , 0.010mmol (S, S, S)-L1, 0.5mL deoxygenated THF and 0.5mL deoxygenated n-propylamine, reacted at 50°C for 30 minutes, and evaporated the solvent under reduced pressure to obtain an iridium catalyst. Under nitrogen protection at 25°C, 2 mL of toluene was added, followed by 0.20 mmol of N-2,2,2-trifluoroethylfluorenoneimine, 0.22 mmol of p-methylphenylallyl methyl carbonate and 0.20 mmol of 1,8- Diazabicycloundec-7-ene, reacted at 25°C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to obtain the product.

[0073] 2) preparation of

[0074] Dissolve the product obtained in step 1) in 1 mL of dichloroethane, add a methanol solution of hydroxylamine acetate (0.5M, 1 mL, prepared in methanol from hydroxylamine hydrochloride, s...

Embodiment 3

[0076] 1) preparation of

[0077] Add 0.005mmol[Ir(COD)Cl] to 25mL reaction tube 2 , 0.010mmol (S, S, S)-L1, 0.5mL deoxygenated THF and 0.5mL deoxygenated n-propylamine, reacted at 50°C for 30 minutes, and evaporated the solvent under reduced pressure to obtain an iridium catalyst. Under nitrogen protection at 25°C, 2 mL of toluene was added, followed by 0.20 mmol of N-2,2,2-trifluoroethylfluorenoneimine, 0.22 mmol of m-methylphenylallyl methyl carbonate and 0.20 mmol of 1,8- Diazabicycloundec-7-ene, reacted at 25°C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to obtain the product.

[0078] 2) preparation of

[0079] Dissolve the product obtained in step 1) in 1 mL of dichloroethane, add a methanol solution of hydroxylamine acetate (0.5M, 2 mL, prepared in methanol from hydroxylamine hydrochloride, s...

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PUM

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Abstract

The invention discloses a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, a preparation method and application thereof. The preparation method of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound comprises the following step of: taking an iridium complex as a catalyst, carrying out catalytic reaction on a substrate 1 and a substrate2 to obtain the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound shown in the formula. The chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compoundcan be applied to preparation of a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II and preparation of a derivative with a chiral tetrahydropyrrole structure. The method disclosed by the invention is simple, low in cost and high in yield, the obtained reaction target compound is good in corresponding selectivity, the yield is 50-95%, the corresponding selectivity excess is greater than 90%, and the method has extremely high reference value for synthesizing a drug containing a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine structural unit.

Description

technical field [0001] The invention belongs to the field of chemistry and medicine, and specifically relates to a chiral α-multi-substituted-α-fluorine-containing homoallylamine compound, its preparation method and application. Background technique [0002] Chiral α-multisubstituted-α-fluorinated homoallylamine structural units widely exist in compounds with important biological activities (such as marketed drugs). Therefore, the efficient, universal and easy-to-use synthesis method of chiral α-polysubstituted-α-fluorinated homoallylamine has been a hot research field in synthetic chemistry. Among them, chiral α-tetrasubstituted-α-fluorinated homoallylamine is difficult to synthesize because of its quaternary carbon chiral center, and there are few reports on efficient catalytic asymmetric synthesis. Fluorine-containing fluorenimines are easy to obtain and stable, and are very good synthons. However, so far, there is no report on the synthesis of chiral α-polysubstituted-...

Claims

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Application Information

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IPC IPC(8): C07C209/52C07C211/28C07C211/29C07C211/30C07C213/02C07C217/62C07C249/02C07C251/20C07D333/20C07D307/52C07D213/36C07D215/12C07D207/10C07B53/00B01J31/02
CPCB01J31/0235C07B53/00C07B2200/07C07C209/52C07C213/02C07C249/02C07D207/10C07D213/36C07D215/12C07D307/52C07D333/20C07C2603/18C07C211/28C07C211/29C07C211/30C07C217/62C07C251/20
Inventor 王春江沈冲
Owner WUHAN UNIV
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