Cyclative MCRs of Azines and Azinium Salts

Since the first discovery by Huigsen and co-workers fifty years ago, a wide range of organic reactions have taken place through the intermediary of the dipolar/zwitterionic species produced by the combination of a neutral nucleophile and an unsaturated electrophile. Nucleophilic initiators including heterocycles may react or play a mediating role based on their nucleophilic nature and reaction conditions. This review highlights the recent developments of the cyclization chemistry of heterocycles using multicomponent reactions (MCRs) - including unusual dearomatizative examples. Heterocycles as very common structural units can often be found in natural and pharmaceutical products. MCRs are environmentally benign and highly atom economic reactions. Their application in the synthesis of biologically active molecules may provide alternatives for the greener synthesis of drugs lowering the carbon footprint of pharmaceutical industries.