Background and overview[1]
Tetrahydrofuran derivatives are important organic intermediates that are present in many natural products (pheromones, polyetherantibiotics and acetogenins) and have gradually become the focus of workers in the fields of organic synthesis and medicinal chemistry. At present, 2,5-disubstituted tetrahydrofuran derivatives are mainly synthesized through various organometallic reagents (such as Al, Ti, Sn, Li, Mg, Si, etc.). The method of synthesizing 2,5-disubstituted tetrahydrofuran derivatives using monoalkyl zinc halide explores another easy way for the synthesis of 2,5-disubstituted tetrahydrofuran derivatives. α,α-diphenyl-γ-butyrolactone is a kind of tetrahydrofuran derivative.
Preparation[1]
Preparation method of 2,5-disubstituted tetrahydrofuran derivative α, α-diphenyl-γ-butyrolactone: using tetrahydrofuran (THF) as solvent, at -40°C ~ -80°C, first The membered ring lactone is reduced to an acetal with diisobutylaluminum hydride (DIBAL), and then, under the catalysis of Lewis acid, monoalkyl zinc halide is used to react with the acetal to synthesize 2,5-disubstituted tetrahydrofuran derivative α,α- Diphenyl-gamma-butyrolactone. Including the following process steps:
1) Under N2 gas protection, dissolve the five-membered ring lactone in tetrahydrofuran, cool to -40°C ~ -80°C, add 2 to 3 times the molar amount of the five-membered ring lactone diisobutyl hydrogenation Aluminum solution, stir for 30 to 45 minutes, then add pyridine with 3 to 4 times the molar amount of the five-membered lactone, 4-dimethylaminopyridine in dichloromethane with 2 to 3 times the molar amount of the five-membered lactone, and five-membered lactone. Add an acid anhydride with 6 to 7 times the molar amount of the lactone, continue stirring for 6 to 12 hours; raise the temperature to 0°C to 10°C, add saturated ammonium chloride solution and potassium sodium tartrate solution, continue stirring for 30 to 50 minutes, and raise the temperature to room temperature. Extract with dichloromethane and dry to obtain a light yellow liquid – acetal;
2) Under N2 gas protection, dissolve the acetal in tetrahydrofuran, cool to -40°C to -80°C, add 3 to 4 times the molar amount of monoalkyl zinc halide of the acetal, and stir for 5 to 10 minutes. Add Lewis acid with 2 to 3 times the molar amount of acetal and stir for 2h to 3h; gradually warm to room temperature, add saturated ammonium chloride solution, extract with dichloromethane, dry, and perform column chromatography to obtain a colorless liquid, which is 2, 5-Disubstituted tetrahydrofuran derivative α, α-diphenyl-γ-butyrolactone.
Main reference materials
[1] CN200710199239.6 Synthesis method of 2,5-disubstituted tetrahydrofuran derivatives
