Synthetic method of multi-chiral-center gamma-lactone compound

A technology of ester compounds and chiral centers, which is applied in the field of synthesis of polychiral center γ-lactone compounds, can solve the problems of single product configuration, difficult substrate construction, and inability to obtain a single configuration.

Inactive Publication Date: 2019-11-22
WUYI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the above method needs to use strong acid and strong base, and it is difficult to construct the substrate
[0004] Chirality plays a very important role in the fields of chemistry, medicine, materials, etc., and most of the polychiral center γ-lactone compounds are synthesized by traditional methods and then obtained by methods such as resolution (CN1872849A) and chiral induction (CN105026382A). For γ-lactone compounds, none of the above methods can obtain a single configuration
In recent years, five-membered ring hemiacetals have been constructed through small molecule catalysis, and then chiral γ-lactone compounds (CN103864731A) have been obtained through oxidation, but this method requires the use of heavy metal oxidants
It can be seen from the above prior art that there is currently no synthetic method for multichiral center γ-lactone compounds that does not require heavy metal oxidants, strong acids and strong bases, single product configuration, and high synthetic yield.

Method used

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  • Synthetic method of multi-chiral-center gamma-lactone compound
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  • Synthetic method of multi-chiral-center gamma-lactone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] 1 mmol R 1 = 4-carbonyl-α,β-unsaturated carboxylic acid of phenyl, 2 mmol R 2 = R 3 = methylated α,β-unsaturated aldehyde, 0.2 mmol R 4 =H,R 5 = phenyl, R 6 = Diaryl prolinol silicon ether of dimethyl tert-butyl silyl, 5 ml of diethyl ether was incubated at 25°C for 48 hours; the solution obtained from the reaction was evaporated to dryness, and 0.1 mmol of triphenylphosphine hydrogen bromide was added to the reaction mixture Salt, 10 mmol 1-methoxy-1-cyclohexene, 10 ml 1,2-dichloroethane at 25 ° C for 5 h, evaporated to dryness, purified by column chromatography, the obtained colorless liquid Ⅰ 224 mg, the yield is : 58%, 99% ee

[0059] The compound of the above compound I is

[0060] HRMS: calculated for C 23 h 30 o 5 [M+H] + : 387.21660, Found 387.21657.HPLC analysis: Chiralpak IC, n-hexane / i-PrOH=90 / 10, flow rate 1.0 ml / min, λ=254nm, t major =11.8min,t minor =14.4min.

Embodiment 2

[0062] 1 mmol R 1 = 4-carbonyl-α,β-unsaturated carboxylic acid of 4-iodophenyl, 2 mmol R 2 = R 3 = methyl α,β-unsaturated aldehyde, 0.2 mmol R 4 =H,R 5 = phenyl, R 6 = Diaryl prolinol silicon ether of dimethyl tert-butyl silyl, 5 ml of diethyl ether was incubated at 25°C for 48 hours; the solution obtained from the reaction was evaporated to dryness, and 0.1 mmol of triphenylphosphine hydrogen bromide was added to the reaction mixture Salt, 10 mmoles of 1-methoxy-1-cyclohexene, 10 ml of 1,2-dichloroethane at 25°C for 5 hours, evaporated to dryness, and purified by column chromatography to obtain 388 mg of white solid II with a yield of: 76%, 99% ee

[0063] The compound of the above-mentioned compound II is

[0064] 35.53, 33.59, 25.81, 23.50, 23.38, 17.96. [α] D20 =11.33, (c 0.3, CHCl 3 ); HRMS: calculated for C 23 h 29 IO 5 [M+H] + : 513.11324, Found 513.11306.HPLC analysis: Chiralpak IC, n-hexane / i-PrOH=90 / 10, flow rate 1.0ml / min, λ=254nm, t major =12.7min,t ...

Embodiment 3

[0066] 1 mmol R 1 = 4-carbonyl-α,β-unsaturated carboxylic acid of 4-methoxyphenyl, 2 mmol R 2 = R 3 = methyl α,β-unsaturated aldehyde, 0.2 mmol R 4 =H,R 5 = phenyl, R 6 = Diaryl prolinol silicon ether of dimethyl tert-butyl silyl, 5 ml of diethyl ether was incubated at 25°C for 48 hours; the solution obtained from the reaction was evaporated to dryness, and 0.1 mmol of triphenylphosphine hydrogen bromide was added to the reaction mixture Salt, 10 mmol 1-methoxy-1-cyclohexene, 10 ml 1,2-dichloroethane at 25°C for 5 h, evaporated to dryness, purified by column chromatography, the obtained colorless liquid III 333 mg, yield For: 80%, 98% ee.

[0067] The compound of the above-mentioned compound III is

[0068] 35.90, 35.18, 33.62, 25.83, 25.82, 23.52, 23.40, 17.97. [α] D20 =-9.33, (c 0.3, CHCl 3 ); HRMS: calculated for C 24 h 32 o 6 [M+H] + : 417.22717, Found 417.22706.HPLC analysis: Chiralpak IC, n-hexane / i-PrOH=80 / 20, flow rate 1.0ml / min, λ=254nm, t major =12.6mi...

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Abstract

The invention relates to a synthetic method of a multi-chiral-center gamma-lactone compound, which comprises the following steps: cyclizing 4-carbonyl-alpha,beta-unsaturated carboxylic acid and alpha,beta-unsaturated aldehyde under the catalysis of diarylprolinol silyl ether, and carrying out functional group protection to synthesize the multi-chiral-center gamma-lactone compound. Compared with the prior art, the invention provides the synthetic method which does not need heavy metal oxidants, strong acids or strong alkalis, which is single in product configuration and high in synthetic yield,and which has a good application prospect, for the multi-chiral-center gamma-lactone compound.

Description

technical field [0001] The invention belongs to the field of organic synthesis chemistry, and in particular relates to a synthesis method of multi-chiral center gamma lactone compounds. Background technique [0002] γ-lactone compounds widely exist in active natural products, spices, pesticides and synthetic drugs. Its intermediates are also widely used in organic materials and dyes. [0003] In recent years, synthesis of achiral γ-lactone compounds generally uses carboxylic acid or carboxylic acid derivatives and alcohols to synthesize γ-lactone compounds through intramolecular dehydration or transesterification (CN101735180A, CN106220591A); hydrogenation is carried out through intermediates Reductive synthesis of γ-lactone compounds (CN104557801A). However, the above method needs to use strong acid and strong base, and the substrate construction is difficult. [0004] Chirality plays a very important role in the fields of chemistry, medicine, materials, etc., and most o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/33C07D409/12
CPCC07D307/33C07D409/12C07B2200/07
Inventor 张书宇江伟蔺军兵张焜
Owner WUYI UNIV
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