Exploiting structural and conformational effects for a site-selective lithiation of azetidines

Interest in molecular structures bearing four-membered heterocycles (FMHs) is growing due to the possibility to explore new regions of the chemical space and get new lead molecules. Our interest in the development of divergent synthesis of functionalized FMHs, prompted us to disclose factors affecting the reactivity of nitrogen-bearing FMHs towards metalating agents. Our investigations demonstrated that structural factors and conformational preferences need to be considered in planning a site-selective functionalization of azetidines. It will be showed how such factors could have pivotal importance in the reactivity of FMHs.