Iodine-mediated Intramolecular Oxidative Cyclization For The Synthesis Of Oxygen-Containing Heterocycles

Recently, the synthetic strategy via direct oxidation of carbon–hydrogen (C–H)and oxygen–hydrogen (O–H) to form a new carbon–oxygen (C–O) bond for theconstruction of oxygen-containing heterocycles has drawn considerable attentionsfrom organic chemists. In this context, significant progress has been made bytransition-metal catalyzed reactions. On the other hand, as the development of greenchemistry, metal-free synthetic protocols are becoming more and more popular.Owing to its low toxicity, availability and eco-friendly nature, molecular iodine hasbeen widely used as an oxidant in organic synthesis, such as protection anddeprotection reaction, oxidative cyclization, and so on.1,3,4-Oxadizoles and1,3-oxazoles are two kinds of important five-memberedoxygen-containing heterocycles. Many compounds with (one of) these two structuralmotifs exhibit extensive biological and pharmaceutical activities, such as, anti-inflammatory, antidiabetic, antivirald, anticancer, etc. As a result, many newmethods for the synthesis of related derivatives have been reported in recent years.In this dissertation, we have successfully developped a concise and efficientiodine-mediated intramolecular oxidative cyclization reaction for the construction ofthe above two heterocycle frameworks:(1) Crude hydrazones, obtained via condensation of aldehydes and hydrazides,were directly oxidized to2,5-disubstituted1,3,4-oxadizoles by iodine in thepresence of base. A range of (aryl, alkyl or vinyl substituted) aldehydes and (aryl oralkyl substituted) hydrazides worked well under the optimal reaction contions andafforded the expected1,3,4-oxadizoles in good yield.(2) In the presence of copper (I)/amino acid as catalysis, N-acyl-enamines wereconverted to a series of functionalized1,3-oxazoles in moderate to excellent yieldvia the oxidative cyclization mediated by iodine.