ChemInform Abstract: Synthesis of Functionalized Amino Acids by Ring-Opening Reactions of Aliphatically Substituted Aziridine-2-carboxylic Esters.

Abstract

Nucleophilic ring-opening reactions of 3-alkylaziridine-2-carboxylic esters are described. Without ring activation at nitrogen, ring opening could only be accomplished with ethereal hydrogen chloride. Introduction of electron-withdrawing activating groups at the nitrogen atom was necessary. Three types of activating groups were used, viz. acyl, alkoxycarbonyl and sulfonyl groups. In the presence of a Lewis-acid catalyst, ring opening with two nucleophiles, namely indole and benzenethiol, could be accomplished. SN2-type attack at C3 was observed exclusively. With Bronsted acids (hydrogen chloride, formic acid, acetic acid), ring opening could also be effected. 3-Formyloxy derivatives could also be prepared by reaction of the activated aziridines with N,N-dimethyl-formamide in the presence of boron trifluoride etherate. Reaction with sodium azide caused some difficulties; complex product mixtures were usually obtained. N-Sulfonylaziridine-2-carboxylic esters gave a mixture of the two possible regioisomers, resulting from attack at C2 and C3. Treatment of N-sulfonylaziridine-2-carboxylic esters with trimethylsilyl azide, however, gave products exclusively ring-opened at C2. On reaction of the activated aziridines with acetonitrile in the presence of boron trifluoride etherate, a ring-expansion reaction was observed, leading to imidazolines. On standing, these heterocyclic compounds slowly hydrolyzed to α,β-diamino carboxylic acid derivatives.