Complexation Phenomena and Dynamics at Work in the Lithiation Reactions of Small-Ring Heterocycles: Regio- and Stereoselectivity

This Microreview focuses on the regio- and stereoselective lithiation of small-ring heterocycles such as aryl-substituted oxiranes, aziridines, azetidines, oxetanes, and tetrahydrofurans highlighting some useful selected synthetic applications extracted from recent literature. It will be shown, in particular, that regio- and stereoselectivity and the configurational stability of the above lithiated species are controlled by a subtle interplay of factors. Aggregation, complexation phenomena, dynamics at the heteroatom of the heterocyclic ring, substitution in both the aryl and the heterocyclic ring, solvent polarity, temperature, and ligands play a crucial role. The ability of the afore-mentioned heterocycles as important directed metalation groups for the arene ortho-functionalization is also discussed as well as the carbene-like nature exhibited by some lithiated epoxides and aziridines. This Microreview focuses on the regio- and stereoselective preparation of α- and ortho-lithiated oxiranes, aziridines, oxetanes, azetidines, and tetrahydrofurans with special emphasis on factors such as carbene-like character, aggregation, complexation phenomena and dynamics which strongly influence their applications to synthetic chemistry. Recent selected examples extracted from the literature are critically analysed and commented.