Mild and efficient preparation method for a-acyloxyenamide compounds and use thereof in synthesis of amide and polypeptide

Use of an α-acyloxyenamide compound in the synthesis of an amide and a polypeptide, comprising the following steps:

• (1) adding 0.2-2 mmol of an α-acyloxyenamide compound and an appropriate amount of dichloromethane solvent to a clean reaction tube, and then adding 0.2-2 mmol of an amine compound, and stirring at a temperature of 0-50° C.;
• and
• (2) detecting the previous step of the reaction by using a TLC analysis;
• after the previous step of the reaction is completed, and separating and purifying by column chromatography to directly obtain an amide compound;
• wherein the chemical reaction formula of Step (2) is:
• in the formula, 3 represents an α-acyloxyenamide compound, 4 represents an amine compound, 5 represents an amide compound, 6 represents an amide by-product;
• R1 is selected from a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, and the like;
• the EWG (electron-withdrawing group) is selected from an alkylsulfonyl group, an arylsulfonyl group, an aryl group, an alkanoyl group, a nitro group, a nitrile group, a phosphono group, a sulfonimide, and the like;
• R2 may be an alkyl or aryl;
• R3 is selected from an alkyl group, an aryl group, an alkenyl group, an alkynyl group, and the like;
• R4 is selected from hydrogen, an aliphatic substituent and an aromatic substituent;
• R5 is selected from hydrogen, an aliphatic substituent, and an aromatic substituent.

A method for synthesizing an amide and a polypeptide by directly using a carboxylic acid and an amine compound as raw materials and under the mediation of a ynamide, comprising the following steps:

• (1) adding 0.2-2 mmol of a carboxylic acid and an appropriate amount of dichloromethane solvent to a clean reaction tube, and then adding 0.2-2 mmol of a ynamide, and stirring at a temperature of 0-50° C.;
• (2) detecting the previous step of the reaction by using a TLC analysis;
• after the previous step of the reaction is completed, directly adding 0.2-2 mmol of an amine compound, or removing the dichloromethane solvent used in the previous step and adding water as a solvent and then adding 0.2-2 mmol of an amine compound, and then stirring at a temperature of 0-50° C.;
• and
• (3) detecting the previous step of the reaction by using a TLC analysis;
• after the previous step of the reaction is completed, and separating and purifying by column chromatography to directly obtain an amide compound;
• wherein the chemical reaction formula of Step (1) and Step (2) is:
• in the formula, 1 represents a ynamide, 2 represents a carboxylic acid, 3 represents an α-acyloxyenamide compound, 4 represents an amine compound, 5 represents an amide compound, 6 represents an amide by-product;
• R1 is selected from hydrogen, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, and the like;
• the EWG (electron-withdrawing group) is selected from an alkylsulfonyl group, an arylsulfonyl group, an aryl group, an carbonyl group, a nitro group, a nitrile group, a phosphono group, a sulfonimide, and the like;
• R2 may be alkyl or aryl;
• R3 is selected from an alkyl group, an aryl group, an alkenyl group, an alkynyl group, and the like;
• R4 is selected from a hydrogen atom, an aliphatic substituent and an aromatic substituent;
• R5 is selected from hydrogen, an aliphatic substituent, and an aromatic substituent.