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Method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation

An indoline, asymmetric technology is applied in the field of catalytic hydrogenation of simple indole to synthesize chiral indoline, can solve the problem of low activity and the like, and achieve the effects of convenient separation, mild reaction conditions and complete conversion

Inactive Publication Date: 2012-02-01
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The Pfaltz group successfully applied the Ir / N, P catalytic system to the asymmetric hydrogenation of N-protected indoles, achieving high enantioselectivity but low activity

Method used

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  • Method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation
  • Method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation
  • Method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation

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Embodiment 1

[0028] Embodiment 1: optimization of conditions

[0029] Put palladium precursor into the reaction flask; palladium trifluoroacetate (0.005 mmol) and chiral ligand: bisphosphine ligand (0.006 mmol), add 1 ml of acetone after nitrogen replacement, stir at room temperature for 1 hour and then concentrate in vacuo to remove Acetone gets the catalyst. Add 1 ml of solvent (dichloromethane and trifluoroethanol (volume ratio 1 / 1)), stirred for 5 minutes, then dissolved the previously prepared catalyst with 2 milliliters of solvent and transferred it to the reaction flask, then put it into the autoclave, fed hydrogen (45 atmospheric pressure), and reacted at 25 ° C for 24 hours. Slowly release the hydrogen gas, stir with 5 ml of saturated sodium bicarbonate at room temperature for 10 minutes to make it alkaline, remove the activator acid, extract with dichloromethane (3×5 ml), combine the organic phases, dry over anhydrous sodium sulfate, filter and spin The solvent is removed by e...

Embodiment 2

[0035] Example 2: Synthesis of various chiral indolines by palladium-catalyzed asymmetric hydrogenation 2

[0036] Put palladium trifluoroacetate (0.005 mmol) and (R)-H8-BINAP (0.006 mmol) into the reaction bottle, add 1 ml of acetone after nitrogen replacement, stir at room temperature for 1 hour and then concentrate in vacuo to remove acetone to obtain a catalyst. In the glove box, add 1 ml of solvent (dichloromethane and trifluoroethanol (1 / 1)) to the reaction bottle previously placed with substrate (0.25 mmol) and L-camphorsulfonic acid (58 mg, 0.25 mmol) , stirred for 5 minutes, then the previously prepared catalyst was dissolved in 2 milliliters of solvent and transferred to the reaction flask, then put into the autoclave, fed with hydrogen (45 atmospheric pressure), and reacted at room temperature for 24 hours. Slowly release the hydrogen gas, stir with 5 ml of saturated sodium bicarbonate at room temperature for 10 minutes to make it alkaline, remove the activator acid...

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Abstract

The invention relates to a method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation, which is characterized in that Bronsted acid is used as the activator and the used catalysis system is a palladium chiral diphosphine complex. The reaction can be carried out under the following conditions: the reaction temperature is 20-50 DEG C; the solvent used in the reaction is a mixed solvent of dichloromethane and 2,2,2-trifluoroethanol (the DCM / TFE volume ratio is 1:1); the hydrogen pressure is 13-45 atmospheres; the substrate-catalyst ratio is 50 / 1; the used metal precursor is palladium trifluoroacetate (Pd(OCOCF3)2); the used chiral ligand is a chiral diphosphine ligand; the used activator is L-camphorsulfonic acid (L-CSA); and unprotected simple 2-substituted indole and 2,3-disubstituted indole can be hydrogenated to obtain the corresponding chiral indoline product, and the enantiomeric excess can be up to 96%. The method has the advantages of convenient operation process, high practicality, easy acquisition of raw materials, good enantioselectivity and high yield.

Description

technical field [0001] The invention relates to a method for synthesizing chiral indoline by using a palladium homogeneous system to catalyze the hydrogenation of simple indole with high enantioselectivity. Background technique [0002] Many compounds containing indoline structures have certain physiological activities, and they are widely found in natural alkaloids and synthetic compounds [(a) Southon, I.W.; Buckingham, J. in Dictionary of Alkaloids; Chapman and Hall: New York , 1989. (b) Neuss, N.; Neuss, M.N. in The Alkaloids; Brossi, A., Suffness, M., Eds.; Academic Press: San Diego, 1990, p.229. (e) Gueritte, F. ; Fahy, J. in Anticancer Agents from Natural Products; Cragg, G.M., Kingstom, D.G.I., Newman, D.J., Fds.; CRC Press: Boca Raton, 2005; p.123.(d) Modern Alkaloids; Fattorusso, E., Taglialatela-Scafati, O., Eds.; Wiley-VCH: Weinheim, 2008, and references therein.], therefore, are widely used in medicine and pesticide chemistry. In addition to attracting people's...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/08C07B53/00B01J31/24C07D209/94C07D209/86
Inventor 周永贵王躲生
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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