A kind of method of synthesizing chiral bridged cyclic lactone

A chiral and bridged ring technology, which is applied in the field of synthesis of chiral bridged ring lactones, can solve the problems of non-compliance with green chemistry, poor atom economy, long synthesis steps, etc., and achieve high industrial application potential, low cost and simple method Effect

Active Publication Date: 2022-07-05
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method needs to pre-install the amide-directing group in the substrate, and then remove it by hydrolysis in the subsequent process, resulting in longer synthesis steps for the reaction and poor atom economy for the reaction, which does not meet the requirements of green chemistry.

Method used

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  • A kind of method of synthesizing chiral bridged cyclic lactone
  • A kind of method of synthesizing chiral bridged cyclic lactone
  • A kind of method of synthesizing chiral bridged cyclic lactone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] General preparation method: under high-purity argon atmosphere, Rh(acac)(CO) 2 (0.5 mg, 0.002 mmol) and the chiral ligand (S,R)-DM-YanPhos (3.6 mg, 0.004 mmol) L1 were dissolved in toluene (1 mL), stirred at room temperature for 10 min, and then 1-substituted Cyclopent-3-en-1-ol (0.2 mmol) 1 . The reaction system was placed in an autoclave, and hydrogen and carbon monoxide (H 2 / CO=5 / 5 atm), stirred at 70°C for 24 hours. After the reaction was finished, the gas in the reactor was slowly released, and the reaction solution was poured into the dichloromethane solution (4mL) of pyridine chlorochromate (PCC, 0.5mmol) and triethylamine (0.1mmol), and the reaction was carried out at room temperature. 12 hours. After the reaction, the solvent was removed under reduced pressure, and the pure bridged cyclic lactone 2 was isolated by column chromatography (petroleum ether / ethyl acetate=10:1, V / V).

[0056] Using this general method, the efficient synthesis of 23 bridged cycli...

Embodiment 2

[0106] Under a high-purity argon atmosphere, Rh(acac)(CO) 2 (0.5 mg, 0.002 mmol) and the chiral ligand (S,S)-Ph-BPE (2.0 mg, 0.004 mmol) L2 were dissolved in toluene (1 mL), stirred at room temperature for 10 min, and then 1-benzene was added cyclopent-3-en-1-ol (0.2 mmol) 1a. The reaction system was placed in an autoclave, and hydrogen and carbon monoxide (H 2 / CO=5 / 5 atm), stirred at 70°C for 24 hours. After the reaction was finished, the gas in the reactor was slowly released, and the reaction solution was poured into the dichloromethane solution (4mL) of pyridine chlorochromate (PCC, 0.5mmol) and triethylamine (0.1mmol), and the reaction was carried out at room temperature. 12 hours. After the reaction, the solvent was removed under reduced pressure, and the pure bridged cyclic lactone 2a (88% yield, 94% ee) was isolated by column chromatography (petroleum ether / ethyl acetate=10:1).

[0107] The yield and enantioselectivity for the synthesis of chiral bridged cyclic lac...

Embodiment 3

[0109] Under a high-purity argon atmosphere, Rh(acac)(CO) 2 (0.5 mg, 0.002 mmol) and the chiral ligand (S,R)-DM-YanPhos (3.6 mg, 0.004 mmol) L1 were dissolved in toluene (1 mL), stirred at room temperature for 10 min, and then 1-benzene was added cyclopent-3-en-1-ol (0.2 mmol) 1a. The reaction system was placed in an autoclave, and hydrogen and carbon monoxide (H 2 / CO=5 / 5 atm), stirred at 70°C for 24 hours. After the reaction, slowly release the gas in the reactor, and pour the reaction solution into pyridine chlorochromate (PCC, 0.5mmol) and Cs 2 CO 3 (0.1 mmol) in dichloromethane solution (4 mL), and reacted at room temperature for 12 hours. After the reaction, the solvent was removed under reduced pressure, and the pure bridged cyclic lactone 2a (85% yield, 94% ee) was isolated by column chromatography (petroleum ether / ethyl acetate=10:1).

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Abstract

The invention discloses a method for synthesizing a chiral bridged cyclic lactone, belonging to the field of organic synthesis. In the present invention, 4-substituted cyclopentene and synthesis gas are used as raw materials, rhodium metal salt and chiral bisphosphine ligand are used as catalysts, and chiral is prepared by asymmetric hydroformylation / intramolecular cyclization / oxidation one-pot series reaction Bridged cyclic lactides. The synthetic method of the invention has cheap and easily available raw materials, high product yield and good enantioselectivity, and the product yield and enantioselectivity can be as high as 95% and 96%. The method of the invention is simple, simple in operation, low in cost, good in atom economy of the reaction, easy to scale up for production, and has high industrial application potential.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a method for synthesizing a chiral bridged cyclic lactone. Background technique [0002] Chiral bridged cyclic lactides are important structural units of natural products and biologically active molecules, especially 2-oxabicyclo[2,2,1]-heptan-3-one and its ring-opening derivatives widely exist in some important in the drug active molecule. For example, the chiral DCK (3',4'-di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khallactone) containing this structure is considered to be a novel anti-AIDS drug candidates. The chiral camphenic acid containing this molecular skeleton is an important intermediate in drug synthesis. In addition, chiral alcohols and chiral amides formed by ring-opening of 2-oxabicyclo[2,2,1]-heptan-3-one are key building blocks of various biologically active molecules, and have potential medicinal prospects. Thus, the synthesis of 2-oxabicyclo[2,2,1]-heptan-3-ones ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/00C07D493/08
CPCC07D307/00C07D493/08C07B2200/07Y02P20/55
Inventor 吕辉李帅龙
Owner WUHAN UNIV
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