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Cross-coupling method of alkyl chloride and phenyl magnesium bromide

A technology of phenylmagnesium bromide and alkyl chloride, used in copper salt catalyzed inactive secondary, copper salt catalyzed cross-coupling of alkyl chloride and phenylmagnesium bromide, tertiary alkyl chloride and phenylmagnesium bromide. In the field of cross-coupling of phenylmagnesium bromide, it can solve the problems such as the difficulty of realizing-carbon cross-coupling

Inactive Publication Date: 2018-03-16
JIANGSU MARINE RESOURCES DEV RES INST LIAN YUNGANG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, current research on copper-catalyzed secondary and tertiary alkyl halide carbons (sp 3 )-carbon cross-coupling reports, mostly focusing on secondary and tertiary alkyl bromides and iodides ((a) Yang, C.-T.; et.al.J.Am.Chem.Soc.2012, 134, 11124. (b) Shen, R.; et.al.Chem.Commun.2012, 48, 9313.), there are few reports on secondary and tertiary alkyl chlorides with low price and easy raw materials (active Secondary alkyl chlorides: Hatcher, J.M.; et.al.J.Am.Chem.Soc.2010, 132, 4546), especially inactive secondary and tertiary alkyl chlorides, copper-catalyzed carbon (sp 3 )-carbon cross-coupling is difficult to achieve

Method used

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  • Cross-coupling method of alkyl chloride and phenyl magnesium bromide
  • Cross-coupling method of alkyl chloride and phenyl magnesium bromide
  • Cross-coupling method of alkyl chloride and phenyl magnesium bromide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1: Cross-Coupling of Cyclohexyl Chloride and Phenylmagnesium Bromide

[0018]

[0019] Add 13 mg (0.1 mmol) copper chloride to the Schlenk reaction tube, use the Schlenk double row tube to evacuate, and pass in argon, repeating three times. Under the state of argon, add 118uL (1.0mmol) chlorocyclohexane, 2.0mL of 2-methyltetrahydrofuran, 2.2mL of phenylmagnesium bromide (2.2mmol, 1.0mol / L, 2-methyltetrahydrofuran solution) , seal the reaction system, put the reaction tube into an oil bath at 80°C, stir and react for 12 hours, add 3mL dilute hydrochloric acid (concentration 1mol / L) and 10mL petroleum ether (boiling range 30-60°C), stir for 10 minutes, Extract and separate liquids, dry over anhydrous magnesium sulfate, and filter. After concentration, the obtained filtrate is separated and purified by silica gel column chromatography, and the eluent is petroleum ether (boiling range: 30-60° C.), and the yield is 63%. 1 H NMR (500MHz, CDCl 3 )δ7.31-7.24 (m, 2H...

Embodiment 2

[0020] Example 2: Cross-Coupling of Cyclopentyl Chloride and Phenylmagnesium Bromide

[0021]

[0022] Add 19 mg (0.1 mmol) of cuprous iodide to the Schlenk reaction tube, use the Schlenk double row tube to evacuate, and pass in argon, and repeat three times. Under argon atmosphere, add 104uL (1.0mmol) cyclopentyl chloride, 2.0mL n-hexane, 1.0mL phenylmagnesium bromide (2.0mmol, 2.0mol / L, 2-methyltetrahydrofuran solution), seal the reaction system , put the reaction tube in an oil bath at 80°C, stir and react for 14 hours, add 3mL dilute hydrochloric acid (concentration 1mol / L) and 10mL petroleum ether (boiling range 30-60°C), stir for 10 minutes, extract and separate the liquid, Dry over anhydrous magnesium sulfate and filter. After concentration, the obtained filtrate is separated and purified by silica gel column chromatography, and the eluent is petroleum ether (boiling range: 30-60° C.). The yield is 70%. 1 H NMR (500MHz, CDCl 3 )δ7.30-7.22 (m, 4H), 7.19-7.14 (m, 1H)...

Embodiment 3

[0023] Example 3: Cross-coupling of 1-phenyl-3-chlorobutane with phenylmagnesium bromide

[0024]

[0025] Add 19 mg (0.1 mmol) of cuprous iodide to the Schlenk reaction tube, use the Schlenk double row tube to evacuate, and pass in argon, and repeat three times. Under the state of argon, add 168uL (1.0mmol) 1-phenyl-3-chlorobutane, 2.0mL of toluene, 2.4mL phenylmagnesium bromide (2.4mmol, 1.0mol / L, 2-methyltetrahydrofuran solution ), seal the reaction system, put the reaction tube into an oil bath at 80°C, stir and react for 12 hours, add 3mL dilute hydrochloric acid (concentration 1mol / L) and 10mL petroleum ether (boiling range 30-60°C), and stir for 10 minutes , extracted and separated, dried over anhydrous magnesium sulfate, filtered, and the resulting filtrate was concentrated and separated by silica gel column chromatography, eluting with petroleum ether (boiling range 30-60° C.), and the yield was 74%. 1 H NMR (500MHz, CDCl 3 )δ7.35-7.27(m, 2H), 7.25(t, J=7.5Hz, 2H...

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Abstract

The invention provides a cross-coupling method of an alkyl chloride and phenyl magnesium bromide, wherein a copper salt is used as a catalyst, the 2-methyltetrahydrofuran solution of phenyl magnesiumbromide is used as a coupling reagent, and the corss-coupling of the inactive secondary / tertiary alkyl chloride and the phenyl magnesium bromide is achieved. According to the present invention, the method has the high yield, does not require the addition of the ligand, is simple and easy to perform, and has important significance in the synthesis of complex molecules such as natural products, chiral drugs, and the like.

Description

technical field [0001] The present invention relates to a copper salt catalyzed cross-coupling method of alkyl chloride and phenylmagnesium bromide, in particular to the cross-coupling of copper salt catalyzed inactive secondary and tertiary alkyl chloride and phenylmagnesium bromide The invention belongs to the field of organic synthesis. Background technique [0002] The carbon of secondary and tertiary alkyl halides (sp 3 )-carbon cross-coupling can obtain coupling products with chiral structure, realize asymmetric metal-catalyzed reaction, and have important significance in the synthesis of complex molecules such as natural products and chiral drugs (Rudolph, A.; Lautens, M.Angew. Chem. Int. Ed. 2009, 48, 2656). Compared with aryl, alkenyl, and primary alkyl halides, secondary and tertiary alkyl halides have higher energy barriers for oxidative addition to metal catalysts, and the alkyl metal reagents generated by oxidative addition are prone to β-H elimination reacti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C1/32C07C13/28C07C15/12C07B37/04
CPCC07B37/04C07C1/326C07C13/28C07C15/12
Inventor 陶传洲孙磊王斌刘洲翟亚东
Owner JIANGSU MARINE RESOURCES DEV RES INST LIAN YUNGANG
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