Executive Summary : | Heterocyclic compounds are essential in therapeutic agents and bioactive natural products. Azidine and aziridine, the three-membered smallest nitrogen-containing compounds, are versatile building blocks for synthesizing many other compounds due to their high reactivity. Azetidine derivatives, the next higher ring nitrogen-containing heterocycle, are slightly more stable and less reactive than their three-membered counterparts. Six and five-membered heterocycles containing drugs dominate in number, while azetidine-containing drugs are gaining attention only recently. Strain-promoted reactivity is increasingly popular in organic synthesis and medicinal chemistry. Recently, elegant synthetic protocols have been developed for azetidines from azabicyclo[1.1.0]butanes (ABBs), such as the generation of ABBLi and the generation of homologated azetidine boronic esters. Highly substituted azabicyclo[1.1.0]butanes (HSABBs) from azirines using an aza-Darzens-like reaction could be a promising approach for finding broad applications in multidisciplinary research. Azabicyclo[1.1.0]butanes (ABBs) display unusual reactivity due to their highly strained bicyclic rings, often reacting with electrophiles across the N-C(3) sigma-bond. These proposed HSABBs could allow the synthesis of several azetidine derivatives, which can be used to synthesize pharmaceutical molecules, natural products, active intermediates of other heterocyclic compounds, and a compound library of potential New Chemical Entities (NCE). |