Síntese de O, N-Heterociclos via reações de ciclização de amidas propargílicas

Abstract

This paper presents a theoretical review of the main synthetic methodologies described in the literature for the synthesis of 1,3-oxazines, oxazoles and oxazolidines derivatives, emphasizing methodologies employed transition metal salts derived of copper, gold, palladium and iron to promote the synthesis of these heterocyclic derivatives via cyclization reactions, employing propargilamides as substrates. Through this research, it realizes the importance of heterocyclic substances, especially concerning their biological and pharmacological properties. There was also the wide applicability of propargilamides as substrates for the synthesis of these classes of compounds via cyclization reactions. In addition, new synthetic protocols were studied for preparation of heterocyclic derivatives containing an organochalcogen group in their structure. For this, three different propargilamides were prepared via acyl substitution reaction between the propargylic amine and benzoyl chloride, followed or not by Sonogashira coupling reaction with iodobenzene and subsequent methylation of the nitrogen atom. The propargilamides were obtained in yields ranging 52-96%. Subsequently, the substrates are subjected to cyclization conditions using copper and iron salts, in the presence of diphenyl diselenide (PhSeSePh), for the synthesis of 1,3- oxazines and oxazolidines derivatives containing a “PhSe” group directly bonded to the heterocyclic ring. Reaction conditions to promote the electrophilic cyclization of the propargilamides were also tested by using PhSeBr as reagent to make this process. However, despite the numerous tests, there was no successful in the development of a synthetic methodology for the preparation of the desired heterocyclic derivatives.