Advances in synthesis and chemistry of azetidines

Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products. Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor. In recent years, a number of methods have been developed for the synthesis of diversely functionalized azetidines. The two classical approaches to formation of azetidine ring are cyclization and cycloaddition reactions of appropriate substrates. Diversely functionalized azetidines are also accessed by transformations of functional groups on azetidine ring. One of the most common examples of functional group transformation is the reduction of azetidin-2-ones to azetidines. The azetidine ring possesses unique reactivity. Its chemical properties may resemble its lower homolog aziridine or higher homolog pyrrolidine depending on electronic and steric environment of the molecule, and reaction conditions employed. The ring-opening reactions of azetidines have been employed as key reactions in design and synthesis of several important compounds. Recently, the ring-expansion reactions of azetidines are drawing considerable attention of researchers for the synthesis of various heterocyclic compounds. The azetidines also serve as ligands in asymmetric catalysis. Azetidines find applications in medicinal chemistry as pharmacological tools in peptidomimetics as unnatural amino acids. This chapter presents advances in synthesis and chemistry of azetidines and its application as a building block in organic synthesis during last 10 years.