Regio- and Stereoselective Lithiation of 2,3-Diphenylaziridines: A Multinuclear NMR Investigation Vito Capriati, ² Saverio Florio,* ,² Renzo Luisi,* ,² Andrea Mazzanti, ‡ and Biagia Musio ² Dipartimento Farmaco-Chimico, UniVersita ` di Bari, Consorzio InteruniVersitario Nazionale Metodologie e Processi InnoVatiVi di Sintesi C.I.N.M.P.I.S., Via E. Orabona 4, I-70125 - Bari, Italy, and Dipartimento di Chimica Organica “A. Mangini”, UniVersita ` di Bologna, Viale Risorgimento 4, I-40136 - Bologna, Italy florio@farmchim.uniba.it; luisi@farmchim.uniba.it ReceiVed January 11, 2008 The R-lithiation-trapping sequence of trans-N-alkyl-2,3-diphenylaziridines (s-BuLi or s-BuLi/TMEDA), taking place with a stereochemistry which dramatically depends on the solvent coordinating ability (inversion of configuration in THF and retention in toluene), has been carefully investigated. 1 H, 13 C, and 7 Li multinuclear NMR investigations at low temperature suggest that two differently configured lithiated aziridines (monomeric cis-1-Li in THF and dimeric trans-1-Li in toluene) are involved. Introduction In a recent paper from our lab, we reported that trans-N- alkyl-2,3-diphenylaziridines undergo exclusively R-lithiation with a stereochemistry that proved to be solvent-dependent 1 (retention of configuration in toluene and inversion in THF). To explain this solvent-dependent stereochemistry, we assumed that two differently configured organolithiums could be in- volved, likely a cis- in THF and a trans-aziridinyllithium in toluene, although starting from the same diphenylaziridine (Scheme 1). To prove the validity of such an assumption, a detailed multinuclear NMR investigation of the neutral and lithiated N-propyl-2,3-diphenylaziridine trans-1 (Figure 1) has been carried out in both THF-d 8 and toluene-d 8 . Results and Discussion Lithiation of trans-N-Propyl-2,3-diphenylaziridine 1 in THF-d 8 in an NMR Tube. Aziridine trans-1 in THF-d 8 at 195 K shows two slowly equilibrating topomers (Figure 1a). 2 Upon treatment of trans-1 with s-Bu 7 Li, a fast deprotonation occurs, giving the corresponding R-lithiated intermediate (Figure 1b). Comparing the 1 H NMR spectra of the neutral and lithiated aziridine, a strong shielding of all the aromatic protons of the phenyl ring directly bonded to the lithiated carbon atom (C R ) testifies that a change in its electronic distribution has occurred. A complete assignment of the above protons has been made possible by a DQF-gCOSY analysis (see the Supporting Information), disclosing that the two H o of the lithiated intermediate have completely different chemical shifts (5.80 and 7.10 ppm) and the H p proton is less shielded than expected (6.20 ppm). 3 The different chemical shifts of the two ortho protons of the phenyl ring bonded to the C R carbon may be ascribed to a reduced mobility of this phenyl ring which rotates slowly around the C R -C i bond. 4 ² Universita ` di Bari. ‡ Universita ` di Bologna. (1) Luisi, R.; Capriati, V.; Florio, S.; Musio, B. Org. Lett. 2007, 9, 1263- 1266. (2) For a definition of topomer, see Binsch, G.; Eliel, E. L.; Kessler, H. Angew. Chem., Int. Ed. 1978, 10, 570-572. (3) (a) Peoples, P. R.; Grutzner, J. B. J. Am. Chem. Soc. 1980, 102, 4709-4715. (b) Hogan, A.-M. L.; O’Shea, D. F. J. Org. Chem. 2007, 72, 9557-9571. 10.1021/jo800069k CCC: $40.75 © 2008 American Chemical Society J. Org. Chem. 2008, 73, 3197-3204 3197 Published on Web 03/22/2008