(N-Isocyanimino)triphenylphosphorane-Mediated One-Pot Efficient Synthesis of Sterically Congested Chloro-2-(5-aryl-1,3,4-oxadiazol-2-yl)-2-propanol Derivatives via Intramolecular Aza-Wittig Reaction

1,3,4-Oxadiazoles have attracted interest in medicinal chemistry as surrogates of carboxylic acids, esters, and carboxamides. They are an important class of heterocyclic compounds that have a wide range of pharmaceutical and biological activities including antimicrobial, anti-fungal, anti-inflammatory, and antihypertensive [1]. Several methods have been reported in the literature for the synthesis of 1,3,4-oxadiazoles. These protocols are multi-step in nature [2]. The most general method involves the cyclization of diacylhydrazides with a variety of reagents, such as thionyl chloride, phosphorus oxychloride or sulfuric acid, usually under harsh reaction conditions. Few reliable and operationally simple examples have been reported for the one-step synthesis of 1,3,4-oxadiazoles, especially from readily available carboxylic acids and acid hydrazides [1,2]. In recent years, several synthetic methods have been reported for the preparation of (N-isocyanimino)triphenylphosphorane (CNNPPh3) 3. There are several reports on the use of (N-isocyanimino)triphenylphosphorane (CNNPPh3) 3 in the synthesis of metal complexes [3]. However, application of 3 in the synthesis of organic compounds is fairly rare [2,3]. As part of our ongoing program to develop efficient and robust methods for the preparation of heterocyclic compounds, we sought to develop a convenient preparation of disubstituted 1,3,4-oxadiazole derivatives 4. Herein we report a hitherto unknown, one-pot three-component reaction, which, starting from readily available choloroaceton 2 affords disubstituted 1,3,4-oxadiazole derivatives 4.