Chiral binaphthalene-aza-polycyclic ligand and preparation method thereof

A technology of polycyclic rings and binaphthyls, which is applied in the field of chiral ligand preparation, can solve the problems of few applications in the field of asymmetric catalysis and uncommon binaphthyl ligands, and achieve the goal of fewer steps, improved catalytic performance, and enhanced coordination ability Effect

Inactive Publication Date: 2020-12-29
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In recent years, chiral ligands based on binaphthyl skeletons have achieved great success in the field of asymmetric catalysis, but binaphthyl ligands containing both axial chirality and central chirality are uncommon. less applications

Method used

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  • Chiral binaphthalene-aza-polycyclic ligand and preparation method thereof
  • Chiral binaphthalene-aza-polycyclic ligand and preparation method thereof
  • Chiral binaphthalene-aza-polycyclic ligand and preparation method thereof

Examples

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preparation example Construction

[0094] Taking compound B2 as an example, its preparation method is introduced in detail, which specifically includes the following steps:

[0095] (1) Dissolve Boc-protected proline methyl ester in an organic solvent, add methylmagnesium bromide Grignard reagent under zero-degree conditions, and react at room temperature for 10 to 18 hours to generate Boc-protected aminoalcohol, and then Separation and purification by column chromatography; wherein the molar ratio of Boc-protected proline methyl ester and methylmagnesium bromide Grignard reagent is 1:4-6;

[0096] (2) Under zero-degree conditions, add 2N ethanol solution of hydrogen chloride to the product separated and purified in step (1) and stir at room temperature for 2 to 3 hours to obtain the corresponding amino hydrochloride, namely compound B2; wherein, Boc protected The molar ratio of amino alcohol and hydrogen chloride ethanol solution is 1:1.5~4.

[0097] Compound B3, Compound B4 and Compound B5 can be prepared re...

Embodiment 1

[0109] A novel chiral binaphthalene-aza five-membered ring ligand: (R a ,S)-2'-((2-(2-Hydroxypropan-2-yl)pyrrolidin-1-yl)methyl)-1,1'-binaphth-2-ol, number L-0, structural formula as follows:

[0110]

[0111] The preparation method of above-mentioned novel chiral binaphthaza five-membered ring ligand comprises the following steps:

[0112] 1. Preparation of compound IV-0

[0113] Synthesis of Compound I

[0114]

[0115]Dissolve (R)-1,1-binaphthol (1 equivalent) in acetone, add potassium carbonate (2 equivalents), slowly add iodomethane (1.05 equivalents) dropwise at room temperature, and heat to reflux for 12 h. After the reaction was detected by TLC, the reaction solvent was removed under reduced pressure, extracted 3 times with ethyl acetate and water, 1 time with saturated brine, dried over anhydrous magnesium sulfate, and oily liquid was obtained under reduced pressure, separated by column chromatography, petroleum ether: acetic acid Ethyl ester=10:1 washing, t...

Embodiment 2

[0166] A novel chiral binaphthalene-aza five-membered ring ligand: (R a ,S)-2'-((2-(3-Hydroxypent-3-yl)pyrrolidin-1-yl)methyl)-1,1'-binaphth-2-ol, code L-1, The structural formula is as follows:

[0167]

[0168] Preparation of Compound V-1:

[0169]

[0170] Dissolve compound IV-0 (1 eq) and B3 (1.5 eq) in acetone, add potassium carbonate (6 eq) and sodium iodide (0.2 eq) to it, and react at room temperature for 24 h. After TLC detects that the reaction is complete, extract with ethyl acetate and water, wash with saturated brine, collect the upper organic phase, dry over anhydrous magnesium sulfate, remove the solvent under reduced pressure, and recrystallize from petroleum ether ethyl acetate to obtain a white solid product (compound V- 1), yield: 90%; 1H NMR (400MHz, DMSO) δ8.10(d, J=9.1Hz, 1H), 8.06–7.90(m, 4H), 7.63(d, J=9.1Hz, 1H), 7.41(t, J=7.4Hz ,1H),7.30(t,J=7.5Hz,1H),7.19(dd,J=15.3,7.8Hz,2H),6.91(d,J=8.5Hz,1H),6.75(d,J=8.5Hz ,1H),3.79(d,J=13.8Hz,1H),3.72(s...

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Abstract

The invention discloses a chiral binaphthalene aza-polycyclic ligand and a preparation method thereof. The ligand has the following structure. The preparation method comprises the following steps: (1)by taking 1, 1 '-binaphthalene 2, 2'-diphenol as a raw material, carrying out methyl protection, Tf2O protection, methylation, aromatic ring substitution and bromination reaction to obtain a 2-bromomethyl -2'-methoxy 1, 1'-binaphthalene derivative (compound V); (2) starting from aza-polycyclic carboxylic acids such as L -or D-proline, L -or D-2-piperidinecarboxylic acid, L- or D-acridine -acid and the like, carrying out derivatization to obtain various amino alcohols (compounds B); and (3) coupling the compound V and the compound B under an alkaline condition and a catalyst, and removing a protecting group to obtain the binaphthalene aza-polycyclic chiral ligand L. The ligand has central chirality and axial chirality at the same time, and can obtain higher reaction activity and enantioselectivity in asymmetric catalytic reaction. The ligands are simple to prepare, raw materials are easy to obtain, and the ligands have important significance for asymmetric synthesis.

Description

technical field [0001] The invention belongs to the field of preparation of chiral ligands in asymmetric catalytic reactions. It specifically relates to a chiral binaphthalene-aza polycyclic ring ligand and a preparation method thereof. Background technique [0002] Chirality plays a vital role in drug activity, and asymmetric catalytic synthesis is the most ideal way to obtain chiral compounds with a single configuration. In asymmetric catalytic reactions, the structure of the chiral ligand determines the stereoselectivity of the reaction. In recent years, chiral ligands based on binaphthyl skeletons have achieved great success in the field of asymmetric catalysis, but binaphthyl ligands containing both axial chirality and central chirality are uncommon. There are also fewer applications. Therefore, it is of great significance to construct a ligand containing multiple chiral centers based on the binaphthyl skeleton. Contents of the invention [0003] The purpose of th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/08B01J31/22C07C33/20C07C29/40
CPCC07D207/08B01J31/2217C07C29/40C07B2200/09C07B2200/07B01J2231/345B01J2531/0241Y02P20/55
Inventor 李月明姚超陈瑶琦黄月孙瑞泽
Owner NANKAI UNIV
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