Method for preparing chirality halohydrin in copper-catalyzed asymmetry hydrosilation mode

An asymmetric, hydrosilation technology, applied in organic chemistry methods, chemical instruments and methods, preparation of hydroxyl compounds, etc., to achieve atomic economy and environmental friendliness, mild reaction conditions, high yield and enantioselectivity.

Inactive Publication Date: 2014-01-22
HANGZHOU NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition to requiring the use of noble metal catalysts, most of these studies are limited to the catalytic asymmetric reduction of α-haloketones, and there are few literature reports on the catalytic asymmetric reduction of β-, γ-, ε-, or other haloketone substrates. involve

Method used

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  • Method for preparing chirality halohydrin in copper-catalyzed asymmetry hydrosilation mode
  • Method for preparing chirality halohydrin in copper-catalyzed asymmetry hydrosilation mode
  • Method for preparing chirality halohydrin in copper-catalyzed asymmetry hydrosilation mode

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: the screening of copper salt

[0027] Using the asymmetric hydrosilylation reaction of 3-chloro-1-phenyl-1-propanone (1a) as a model reaction, using (S)-P-Phos as a chiral ligand, toluene as a solvent, PhSiH 3 A screening of different copper salts was carried out for silanes with the following reaction:

[0028]

[0029] The specific operation of the catalytic asymmetric hydrosilylation reaction is as follows: Cu salt (9.0×10 –3 mmol) and the chiral ligand (S)-P-Phos (1.9mg, 3.0×10 –3 mmol) into a 25mL reaction tube with a stirring bar, add 0.5mL toluene, stir at room temperature for 15 minutes, then add PhSiH 3 (45μL, 3.6mmol), continue to stir for 10 minutes, add 3-chloro-1-phenyl-1-propanone (1a, 50.6mg, 0.3mmol) in toluene (0.5mL) solution, stir vigorously, and use TLC to detect the reaction process . After reacting for 4 hours, add 10% hydrochloric acid solution (2mL), extract with ether (3×3mL), combine the organic phases, wash with water, anh...

Embodiment 2

[0034] Example 2: Screening of Chiral Dual Phosphorous Ligands

[0035] Using the asymmetric hydrosilylation reaction of 3-chloro-1-phenyl-1-propanone (1a) as a model reaction, Cu(OAc) 2 ·H 2 O is the catalyst precursor, toluene is the solvent, PhSiH 3 Screening of different chiral ligands for silane, the reaction formula and the structure of each chiral diphosphorus ligand are as follows:

[0036]

[0037] The specific operation of catalytic asymmetric hydrosilylation reaction is as follows: Cu(OAc) 2 ·H 2 O (1.8mg, 9.0×10 –3mmol) and chiral bisphosphorus ligand (3.0×10 –3 mmol) into a 25mL reaction tube with a stirring bar, add 0.5mL toluene, stir at room temperature for 15 minutes, then add PhSiH 3 (45μL, 3.6mmol), continue to stir for 10 minutes, add 3-chloro-1-phenyl-1-propanone (1a, 50.6mg, 0.3mmol) in toluene (0.5mL) solution, stir vigorously, and use TLC to detect the reaction process . After reacting for 4 hours, add 10% hydrochloric acid solution (2mL), ex...

Embodiment 3

[0042] Embodiment 3: the influence of solvent and temperature of reaction

[0043] Using the asymmetric hydrosilylation reaction of 3-chloro-1-phenyl-1-propanone (1a) as a model reaction, Cu(OAc) 2 ·H 2 O is the catalyst precursor, (S)-P-Phos or (S)-Xyl-P-Phos is the chiral diphosphorus ligand, PhSiH 3 Screening of different solvents and optimization of reaction temperature were carried out for silane, and the reaction formula is as follows:

[0044]

[0045] The specific operation of catalytic asymmetric hydrosilylation reaction is as follows: Cu(OAc) 2 ·H 2 O (1.8mg, 9.0×10 –3 mmol) and chiral bisphosphorus ligand (3.0×10 –3 mmol) into a 25mL reaction tube with a stirring bar, add 0.5mL solvent, stir at room temperature for 15 minutes, then add PhSiH 3 (45μL, 3.6mmol), continue to stir for 10 minutes, add 3-chloro-1-phenyl-1-propanone (1a, 50.6mg, 0.3mmol) in a solvent (0.5mL) solution, stir vigorously, and use TLC to detect the reaction process . After reacting f...

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Abstract

The invention discloses a method for preparing chirality halohydrin in a copper-catalyzed asymmetry hydrosilation mode. In the prior art, mostly a noble metal catalyst is needed, the research is generally limited in catalysis asymmetry reduction of alpha-haloketone, and documents about catalysis asymmetry reduction of beta-, gamma-, epsilon- or other haloketone substrates are less related. The method disclosed by the invention comprises preparing chirality gamma-, delta- or zeta-haloalkyl aryl alcohol from beta-, gamma-, epsilon-haloalkyl aryl ketone in a copper catalysis asymmetry hydrosilation reduction mode, or preparing chirality beta-, gamma- or delta-haloalkyl aryl alcohol from alpha-, beta- or gamma-haloalkyl aryl ketone in the copper catalysis asymmetry hydrosilation reduction mode. The method adopts a non-noble metal catalyst, the raw material is easy to obtain, nitrogen protection is not needed, the reaction condition is mild, the operation is simple, and the yield and the enantioselectivity of the reaction are high.

Description

technical field [0001] The invention relates to the field of asymmetric synthesis of chiral fine chemicals, and relates to a method for preparing chiral halohydrins by copper-catalyzed asymmetric hydrosilylation, in particular to a preparation method for chiral halohydrins and derivatives thereof. Background technique [0002] Optically active halogenated alcohols are a particularly important class of structural elements, which can be used to synthesize many structurally meaningful organic compounds, including chiral epoxy compounds, diols, and amino alcohols; they are also the key to the synthesis of some chiral drugs Intermediates, including drugs for the treatment of metabolic disorders and antidepressants, antagonists, antiarrhythmic drugs, cholesterol-lowering drugs and agricultural fungicides, etc. [a) D.W.Robertson, J.H.Krushinski, R.W.Fuller, J.D.Leander, J.Med. Chem.1988,31,1412–1417;b)E.J.Corey,G.A.Reichard,Tetrahedron Lett.1989,30,5207–5210;c)H.-L.Liu,B.H.Hoff,T.A...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C33/46C07C29/145C07C43/23C07C41/26C07D333/16C07C217/48C07C213/06C07D333/20B01J31/24
CPCB01J31/2409B01J2531/16C07B41/02C07B2200/07C07C29/143C07C41/26C07C213/06C07D333/16C07D333/20C07C33/46C07C43/23C07C217/48
Inventor 吴静周继宁李世军
Owner HANGZHOU NORMAL UNIVERSITY
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