ORIGINAL RESEARCH A computational study of the effect of C-lithiation on the NMR properties (chemical shifts and coupling constants) of aziridines Vito Capriati Æ Saverio Florio Æ Renzo Luisi Æ Biagia Musio Æ Ibon Alkorta Æ Fernando Blanco Æ Jose ´ Elguero Received: 26 March 2008 / Accepted: 24 July 2008 / Published online: 27 August 2008 Ó Springer Science+Business Media, LLC 2008 Abstract A DFT (B3LYP/6-311??G(d,p) study of a series of N-H, N-methyl and N-propyl aziridines and their C-lithium derivatives has been carried out in order to explore their configurational as well as their NMR prop- erties ( 1 H and 13 C). The results agree fairly well with experimental observations [Org Lett 9:1263, 2007 and J Org Chem 73, 2008 (73:3197)] and reveal the existence of lithium-N(lone pair) and lithium C(aromatic) interactions. Keywords Aziridines  Lithium derivatives  B3LYP  GIAO Introduction It has recently been reported that the regio- and stereose- lective lithiation of N-propyl-2,3-diphenylaziridines dramatically depends on the reaction conditions (i.e. the used solvent) and on the stereochemistry of the carbon and nitrogen atoms of the aziridine ring [1]. Moreover, a multinuclear NMR investigation carried out on the lithiated intermediates threw light on the observed stereoselectivity (inversion of configuration in THF and retention in toluene) [2]. From these papers an important collection of NMR data (chemical shifts, coupling constants and ste- reochemistry at the N-substituent) has been taken, in both solvents, for compounds 1, 2, 3 and 4 (Fig. 1). Comparison of experimental data [1, 2] leads to the following conclusions: (i) solvent effects are negligible in neutral molecule 1; (ii) in THF, the trans ? cis isomeri- zation produces weak effects in 1 H NMR (0.4 ppm or less with the exception of one of the protons of the a-CH 2 group) and medium ones in 13 C NMR (-4.8 and ?2.4 ppm); (iii) a-lithiation shifts the signals of the ring carbon atoms going from 1 to 3 in toluene by ?22.0 (CLi) and ?14.8 ppm (CH) and from 2 to 4 in THF by ?30.8 (CLi) and ?7.7 ppm (CH); (iv) the lithium chemical shifts (4 0 and 3 1.3 ppm) are not useful probes due to their small range of variation [3]; and (v) the difference of 1 J CLi coupling constants is about 12 Hz between lithiated aziri- dines 3 in toluene (19.0 Hz) and 4 in THF (31.0 Hz). We decided to study these compounds with the tech- niques available in computational chemistry, which offer the advantage of completeness, allowing the study of other conformations, and to assign some NMR signals by calcu- lating the absolute shieldings. We have selected some simple models to explore the conformational space in a previous step before examining the real case of compounds 1–4. Computational details DFT-optimized geometries of the molecules investigated in this study have been obtained using the B3LYP functional [4] with the 6-311??G(d,p) basis set [5]. Vibrational frequencies were computed to confirm that each species is an equilibrium structure on the potential energy surface. DFT coupling constants [6], including all four terms, were Electronic supplementary material The online version of this article (doi:10.1007/s11224-008-9365-0) contains supplementary material, which is available to authorized users. V. Capriati  S. Florio (&)  R. Luisi  B. Musio Dipartimento Farmaco-Chimico, Universita ` di Bari, C.I.N.M.P.I.S., Via E. Orabona 4, Bari 70125, Italy e-mail: florio@farmchim.uniba.it I. Alkorta (&)  F. Blanco  J. Elguero Instituto de Quı ´mica Me ´dica (CSIC), Juan de la Cierva 3, Madrid 28006, Spain e-mail: ibon@iqm.csic.es 123 Struct Chem (2008) 19:785–792 DOI 10.1007/s11224-008-9365-0