Organic catalyst and ligand with rigid spiro[indane-1,2'-pyrrolidine] skeleton, synthesis and application

A catalyst and compound technology, applied in the field of asymmetric catalytic synthesis, can solve the problems of poor enantioselectivity, harsh reaction conditions and high cost of raw materials

Active Publication Date: 2019-04-26
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the prior art, P, P-, P, N- and N, N-type bidentate ligands are used to catalyze asymmetric addition and asymmetric coupling reactions, especially for the synthesis of biaryls However, there are still obvious disadvantages such as active base, poor enantioselectivity, and narrow scope of substrate application,

Method used

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  • Organic catalyst and ligand with rigid spiro[indane-1,2'-pyrrolidine] skeleton, synthesis and application
  • Organic catalyst and ligand with rigid spiro[indane-1,2'-pyrrolidine] skeleton, synthesis and application
  • Organic catalyst and ligand with rigid spiro[indane-1,2'-pyrrolidine] skeleton, synthesis and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] This example provides a kind of (1R)-1'-[(R)-2-hydroxyl-1-phenylethyl)]-spiro[indane-1,2'-pyrrolidine]-5'-one ( Compound 5a) and (1S)-1′-[(R)-2-hydroxy-1-phenylethyl)]-spiro[indan-1,2′-pyrrolidine]-5′-one (compound 5b ) preparation method, the reaction formula is as follows, comprising the steps:

[0138]

[0139] (1) 400mmol of ethyl levulinate was added in 100mL of benzene, then 23mL (400mmol) of glacial acetic acid and 7.3mL (80mmol) of hexahydropyridine were added thereto as reactant and catalyst, stirred and heated to a slight boil; Dissolve 200mmol of benzaldehyde in 100mL of benzene, drop it into the mixed solution of ethyl levulinate within 2 hours, reflux and separate water for 6 hours under heating at 90°C, and carry out aldol condensation reaction. After the reaction is complete, successively use 2N HCl (2×100mL), 10% NaHCO 3 solution, saturated NaCl solution, and the organic phase was washed with anhydrous NaCl 2 SO 4 After fully drying and concentrat...

Embodiment 2

[0157] In the present embodiment, reaction formula is as the reaction formula in embodiment 1, and the difference of preparation method and embodiment 1 is:

[0158] In step (1), the consumption of ethyl levulinate is 240mmol, the consumption of glacial acetic acid is 20mmol, the consumption of hexahydropyridine is 1.8mL (20mmol), the consumption of other reactants is unchanged, and the dropping time is 1.5h. Using the operation method of Example 1, ethyl (trans)-6-phenyl-4-oxo-5-hexenoate (compound 1a) (34.8 g, 75%) was obtained.

[0159] In step (2), the dosage of compound 1a is 70mmol, the dosage of 10% Pd / C catalyst is 74mg, wherein the effective substance of Pd is 0.07mmol, and the dosage of other reactants is unchanged. Using the operation method of Example 1, ethyl 6-phenyl-4-oxohexanoate (compound 2a) (16.5 g, 100%) was obtained.

[0160] In step (3), the amount of NaOH is 3.96mmol, and the amount of all the other reactants is constant. Adjust the pH of the system to...

Embodiment 3

[0164] In the present embodiment, reaction formula is as the reaction formula in embodiment 1, and the difference of preparation method and embodiment 1 is:

[0165] In step (1), the consumption of ethyl levulinate is 600mmol, the consumption of glacial acetic acid is 400mmol, the consumption of hexahydropyridine is 400mmol, the consumption of other reactants is unchanged, the reaction temperature is 90°C, and the dropwise addition time is 5h. Using the operation method of Example 1, ethyl (trans)-6-phenyl-4-oxo-5-hexenoate (compound 1a) (37.1 g, 80%) was obtained.

[0166] In step (2), the amount of compound 1a was 70mmol, the amount of 10% Pd / C catalyst was 7.4g, wherein the effective substance amount of Pd was 7.0mmol, and the amount of other reactants was unchanged, and the reaction was carried out for 12h. Using the operation method of Example 1, ethyl 6-phenyl-4-oxohexanoate (compound 2a) (16.4 g, 100%) was obtained.

[0167] In step (3), the amount of NaOH used was 8.2...

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Abstract

The invention discloses an organic catalyst and ligand with rigid spiro[indane-1,2'-pyrrolidine] skeleton, synthesis and application. The invention further discloses synthesis methods thereof. The method raw material is cheap and easy to obtain; the reaction condition is mild; a sharp reaction condition, metal reagent sensitive to the air and the moisture, and the transition catalyst with expensive price cannot be used; the reaction process is simple and easy, and the requirements on the device and equipment for synthesis and separation are low. The synthesized chiral molecule can be served asan excellent catalyst or ligand for asymmetric synthesis reaction, and has potential medicine application.

Description

technical field [0001] The invention belongs to the technical field of asymmetric catalytic synthesis, and specifically relates to a class of organic catalysts with rigid spiro[indane-1,2'-pyrrolidine] skeletons, ligands and their synthesis and application. Background technique [0002] Chirality is a fundamental property of nature. Chiral compounds exist widely in nature, and many of them are used as drug molecules. Natural products produced in vivo or metabolized by animals, plants, and microorganisms are an important source of chiral drugs. The asymmetric synthesis catalyzed by chiral catalysts is an important way to obtain enantiomerically pure chiral building blocks and chiral drugs, and it is also a breakthrough and supplement to the extraction of natural chiral compounds. The chirality contained in the chiral catalyst can be transferred to the chiral product molecule during the catalytic reaction. The chiral structure of the catalyst is crucial to obtain enantiomer...

Claims

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Application Information

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IPC IPC(8): C07F9/572
Inventor 焦鹏张金霞李莎莎
Owner BEIJING NORMAL UNIVERSITY
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