Ten years of progress in the synthesis of six-membered N-heterocycles from alkynes and nitrogen sources

Abstract

The purpose of this review is to highlight ten years of success in the synthesis of six-membered N-heterocycles using alkynes and nitrogen sources as substrates. It is our hope summarizing these methods would be very useful for the chemists who are interested in the synthesis of heterocycles.

Introduction

The organic chemistry and the development of heterocycles began to walk together since first compounds were isolated from plants and microorganisms. Nowadays, the majority of articles published in different areas dealing with natural compounds or medicines are related to heterocycles. In this way, it is unquestionable the importance of heterocycles in chemistry, medicine [[1], [2], [3], [4], [5], [6], [7]] and in our life [8]. Among them, the nitrogen-containing heterocycles receive the greatest attention in studies associated with synthesis, reactivity, and biological evaluation. It is because N-heterocycles are present in a wide variety of compounds with not only biological but also industrial importance [[9], [10], [11]]. In addition, N-heterocycles can be used as intermediates to the synthesis of other compounds. Consequently, a number of very efficient approaches have been developed for their synthesis. In spite of these methods, both metal-free and metal-catalyzed [[12], [13], [14]] cyclization reactions of unsaturated substrates have emerged as the best choices for the preparation of these compounds. In this context, alkynes are probably the most versatile and widely used substrates because they behave as both an electrophile and a nucleophile [15,16]. In addition, the substrates containing an amine moiety can undergo a nucleophilic addition to alkynes becoming a suitable partners to promote several transformations [17]. The cooperative action between alkynes and nitrogen compounds is a useful alternative to the synthesis of N-heterocycles. We believe that summarizing the methods for the preparation of six-membered N-heterocycles, which combine alkynes and nitrogen-containing compounds as substrates, would be very useful for the chemists. Because many advances in the synthesis of these compounds have been published in the last years, the purpose of this review is to highlight ten years of these achievements. In addition, the number of articles found in the literature on this topic is very large; therefore, to cover as many as possible we summarized the results in equations and tables, avoiding in some cases lengthy discussions. For the same reason, N-heterocycles containing other heteroatoms, such as oxygen, sulfur, selenium, silicon, phosphor, among others, will be not described in this review. We apologize for this limitation and the colleagues whose works have not been cited in the review. To facilitate presentation, the review is organized by the name of N-heterocycle in alphabetical order. Each N-heterocycle is further subdivided into the nature of the cyclization reaction used for their preparation; transition-metal catalyzed cyclization will appear first followed by the transition metal-free approaches.