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Cyclopropyl substituted allyl alcohol and asymmetric synthesis method thereof

A technology of allyl alcohol and cyclopropyl, which is applied in the field of asymmetric catalysis to achieve the effect of simple synthesis, stable ligand and convenient experimental operation

Active Publication Date: 2017-12-15
CHINA THREE GORGES UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, there are few reports on the asymmetric transfer hydrogenation synthesis of cyclopropyl-substituted chiral allyl alcohols

Method used

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  • Cyclopropyl substituted allyl alcohol and asymmetric synthesis method thereof
  • Cyclopropyl substituted allyl alcohol and asymmetric synthesis method thereof
  • Cyclopropyl substituted allyl alcohol and asymmetric synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: Catalyst A-J, p-(E)-styryl cyclopropanemethanol asymmetric synthesis

[0029]

[0030] Add 0.01 mmol of catalysts numbered A-J to 10 ml of Schlenk test tubes, add 0.2 mmol (E)-styryl cyclopropyl ketone, add hydrogen source, different solvents, seal the test tubes, and replace the gas with nitrogen three times , 50°C for 24 hours. After the reaction, wash with water, extract the aqueous phase with ethyl acetate 3 times, combine the organic phases and concentrate to dryness, use catalyst E, formic acid: triethylamine (5:2, V / V) when the yield and enantiomeric excess value The highest, the isolated yield is 90% (petroleum ether: ethyl acetate = 3:1), the ee value of the enantiomeric excess of 81% of the product (S,E)-styryl cyclopropanol was determined by HPLC, and the results are shown in Table 1 shown. HPLC separation conditions: chiral column Daicel OD-H column, mobile phase: n-hexane / isopropanol=90:10 (volume ratio), flow rate: 1.0 ml / min, wavelength...

Embodiment 2

[0033] Example 2: Asymmetric Synthesis of (S, E)-(4-Methylstyryl) Cyclopropanol

[0034]

[0035] Catalyst E (0.01mmol, 3.26mg) was added to a 10ml Schlenk test tube, and 0.2mmol (E)-(4-methylstyryl) cyclopropanone, formic acid: triethylamine (5:2, v / v) 1 mL, seal the test tube, replace the gas with nitrogen three times, and react at 50°C for 24 hours. After the reaction was finished, the reaction was washed with water, the aqueous phase was extracted 3 times with ethyl acetate, combined and concentrated to dryness, the isolated yield: 93% (petroleum ether: ethyl acetate = 3:1), and the product (S, E)-( 4-Methylstyryl)cyclopropanemethanol has an enantiomeric excess of 73% ee. HPLC separation conditions: chiral column Daicel OD-H column, mobile phase: n-hexane / isopropanol=95:5 (volume ratio), flow rate: 1.0 ml / min, wavelength: 254 nm, column temperature: 30 degrees Celsius, t1=12.28 minutes, t2=14.00 minutes; 1 H NMR (400MHz, CDCl 3):δ=7.33(t, J=7.2Hz, 2H), 7.16(t, J=6.8...

Embodiment 3

[0036] Example 3: Asymmetric Synthesis of (S, E)-4-trifluoromethylstyryl) cyclopropanemethanol

[0037]

[0038] Catalyst E (0.01mmol, 3.26mg) is added in the Schlenk test tube of 10 milliliters, adds 0.2mmol0.2mmol (E)-(4-trifluoromethyl styryl) cyclopropanone, formic acid: triethylamine ( 5:2, v / v) 1mL, seal the test tube, replace the gas with nitrogen three times, and react at 50°C for 24 hours. Washed with water after the reaction, the aqueous phase was extracted 3 times with ethyl acetate, combined and concentrated to dryness, the isolated yield: 95% (petroleum ether: ethyl acetate=3:1), HPLC assay product (S, E)-( 4-Trifluoromethylstyryl)cyclopropanol has an enantiomeric excess of 82% ee. HPLC separation conditions: chiral column Daicel OD-H column, mobile phase: n-hexane / isopropanol=99:1 (volume ratio), flow rate: 1.0 ml / min, wavelength: 254 nm, column temperature: 30 degrees Celsius, t1=30.51 minutes, t2=32.84 minutes; 1 H NMR (400MHz, CDCl 3 ): δ=7.60(d, J=8.4H...

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Abstract

The invention relates to cyclopropyl substituted allyl alcohol and an asymmetric synthesis method thereof. The method comprises the following steps: by taking monosulfonyl chiral diamine and a complex of metals ruthenium, rhodium and iridium as a catalyst, carrying out an asymmetric transfer hydrogenation reaction, thereby obtaining the cyclopropyl substituted allyl alcohol. The method is mild in reaction conditions, simple and convenient to operate, readily available in raw materials, wide in substrate application range and high in enantioselectivity and has important application prospects in the aspect of synthesizing a psoriasis treatment drug calcipotriol.

Description

technical field [0001] The invention belongs to the technical field of asymmetric catalysis, and in particular relates to a cyclopropyl-substituted allyl alcohol and an asymmetric synthesis method thereof. Background technique [0002] Cyclopropyl-substituted chiral allyl alcohol is an intermediate in the synthesis of many natural products, drugs, pesticides, and biologically active substances, such as calcipotriol for the treatment of psoriasis, (Angew.Chem.Int.Ed.2013,52,1890 ), as a currently listed drug, calcipotriol has a good curative effect in the treatment of psoriasis, but due to the cyclopropyl group contained in its molecule, and the construction of multiple chiral hydroxyl groups, there are many steps in the synthesis of this type of compound, and the efficiency is low. A series of deficiencies. It is of great value to develop new asymmetric synthesis methods with simple operation, economy and mild reaction conditions. Asymmetric transfer hydrogenation has the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C33/38C07C29/143C07C29/145C07C29/76C07F17/02C07C43/23C07C41/26C07C41/36C07C205/26C07C201/12C07C201/16
CPCC07B2200/07C07C29/143C07C29/145C07C29/76C07C33/38C07C41/26C07C41/36C07C43/23C07C201/12C07C201/16C07C205/26C07F17/02
Inventor 周海峰刘森生刘祈星刘欢王春琴
Owner CHINA THREE GORGES UNIV
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