Regioselective Lithiation of Aziridines: Synthetic Applications and NMR Structural Investigation

Abstract: The “Aziridinyl Anion Methodology” (AAM), based on the metalation-trapping sequence of an easily available parent aziridine, has become an attractive way for the synthesis of functionalized aziridines.1 In our studies concerning the lithiation of N-unactivated aziridines we disclosed recently that the regioselectivity of the deprotonation reaction depends on the nature of the substitution on the carbon and nitrogen atoms of the aziridine ring as well as on the polarity of the medium in which the reaction is performed. In this communication it will be reported that a regioselective α-lithiation of trans N-alkyl-2,3-diphenylaziridines occurs with inversion of configuration in a polar solvent (i.e. THF) and retention in a non polar solvent (i.e. toluene) making these results useful for synthetic purposes. A deep multinuclear (1H, 13C, 7Li, 6Li) 1D and 2D NMR investigation of the lithiated intermediates in different solvents has been performed with the aim to demonstrate that probably two differently configured organolithium species could be involved. The role of the nitrogen configuration on the regioselectivity of the lithiation will also be discussed for several functionalized aziridines