Ring Expansion of 3-Oxetanone-Derived Spirocycles: Facile Synthesis of Saturated Nitrogen Heterocycles

摘要

recent years, oxetanes have received attention among medicinal chemists as they can improve key physicochemical and metabolic properties of potential drugs. As a result, new synthetic methods to incorporate oxetanes in biologically active scaffolds have been developed and a variety of oxetane building blocks have become commercially available. However, the potential of these novel structures to serve as synthetic intermediates remains less thoroughly explored. Herein, we report a novel strategy for the facile synthesis of biologically important saturated nitrogen hetero-cycles which is based on the unique reactivity of 3-oxetanone (1) derived aminals, hemiaminal'ethers, and thio ethers 3 (Scheme 1). The method provides convenient access to a variety of functionally rich morpholines (X = O), thiomor-pnolmes (X = S), and piperazines (X = NR) in a stereocon-trolled manner and good yields.