An Unexpected KI-promoted nucleophilic substitution reactions between 2-acyloxy-2H-azirines and carboxylic acids

【作者】 杨坤； 段希焱； 马军营；

【Author】 Kun Yang;Xi-yan Duan;Jun-ying Ma;School of Chemical Engineering and Pharmaceutics, Henan University of Science and Technology;

【机构】 School of Chemical Engineering and Pharmaceutics, Henan University of Science and Technology；

【摘要】 2H-azirines skeleton is a key heterocyclic motif that is responsible for a broad spectrum of biological and pharmacological activities, and has become a key substructure in drug design.Although there are two strategies for nucleophilic replacement between 2-substituent of2H-azirines and nucleophiles, these processes are limited to those 2-substituted of 2H-azirines which possessed halogen and benzotriazole as leaving group. On the other hand, the nucleophilic replacement of 2-substituent of 2H-azirines with O-nucleophiles has never been explored. So, a mild and efficient method under metal-free conditions with 2-substituent of 2H-azirines substrate scope beyond 2-halo-2H-azirines and 2-(Benzotriazol-1-yl)-2H-azirines reacting with O-nucleophile would be in high demand.In this work, we described an unprecedented nucleophilic substitution of 2-acyloxylated of2H-azirines with carboxylic acids under metal-free conditions. In contrast to conventional nucleophilic substitution in which nucleophiles displace halide or hydroxyl group, in this paper we describe the KI-promoted nucleophilic substitution in which carboxylic acids served as nucleophiles displace the acyloxy group of 2-acyloxylated of 2H-azirines. This new finding opened door for us to realize the nucleophilic substitution in which carboxylic acids displace the acyloxy group. Other than the importance of the product, the convenience of the procedure, the specificity of the reaction, and the low cost of the environmentally benign iodine reagent are among the highlighted characteristics of the new method herein reported.更多还原

【Abstract】 2H-azirines skeleton is a key heterocyclic motif that is responsible for a broad spectrum of biological and pharmacological activities, and has become a key substructure in drug design.Although there are two strategies for nucleophilic replacement between 2-substituent of2H-azirines and nucleophiles, these processes are limited to those 2-substituted of 2H-azirines which possessed halogen and benzotriazole as leaving group. On the other hand, the nucleophilic replacement of 2-substituent of 2H-azirines with O-nucleophiles has never been explored. So, a mild and efficient method under metal-free conditions with 2-substituent of 2H-azirines substrate scope beyond 2-halo-2H-azirines and 2-(Benzotriazol-1-yl)-2H-azirines reacting with O-nucleophile would be in high demand.In this work, we described an unprecedented nucleophilic substitution of 2-acyloxylated of2H-azirines with carboxylic acids under metal-free conditions. In contrast to conventional nucleophilic substitution in which nucleophiles displace halide or hydroxyl group, in this paper we describe the KI-promoted nucleophilic substitution in which carboxylic acids served as nucleophiles displace the acyloxy group of 2-acyloxylated of 2H-azirines. This new finding opened door for us to realize the nucleophilic substitution in which carboxylic acids displace the acyloxy group. Other than the importance of the product, the convenience of the procedure, the specificity of the reaction, and the low cost of the environmentally benign iodine reagent are among the highlighted characteristics of the new method herein reported.更多还原