Synthesis of 2-pyrazoline-5-carboxylic acid derivatives using trimethylsilyldiazomethane

1,3-Dipolar cycloaddition reaction of α,β-unsaturated esters, amides or nitriles with diazomethane or trimethylsilyldiazomethane can be one of the powerful methods for the synthesis of pyrazoline building blocks, particularly, 2pyrazoline-5-carboxylic ester (1), amide or nitrile which can be used as chiral precursors in the preparation of several unnatural amino acids (2 and 4) and as building blocks, pyrazoline derivative (3), for the asymmetric synthesis. But, prior studies on the cycloadditions of α,βunsaturated ester with diazoalkanes or trimethylsilyldiazomethane had indicated that the pyrazoline (5) initially formed in such cycloadditions readily isomerized (1,3proton migration) to the corresponding conjugated 2pyrazoline-3-carboxylic ester (6), not to the desired 2pyrazoline-5-carboxylic ester (1) (Scheme 2). Also, reaction of α,β-unsaturated nitrile with trimethylsilyldiazomethane gave the same result (Scheme 3) and so far no single example has been reported for the cycloaddition of diazomethane or trimehtylsilyldiazomethane with α,β-unsaturated amide for the synthesis of 2-pyrazoline-5-carboxamide. These reports prompted us to attempt synthesis of 2pyrazoline-5-carboxylic ester, amide and nitrile through controlling the reaction before 1,3-proton migration. Therefore, under several conditions, we investigated cycloaddition reaction of α,β-unsaturated ester, amide and nitrile with trimethylsilyldiazomethane.