Solvent- and Temperature-Dependent Functionalisation of Enantioenriched Aziridines
Article first published online: 12 NOV 2010
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chemistry - A European Journal
Volume 17, Issue 1, pages 286–296, January 3, 2011
How to Cite
de Ceglie, M. C., Musio, B., Affortunato, F., Moliterni, A., Altomare, A., Florio, S. and Luisi, R. (2011), Solvent- and Temperature-Dependent Functionalisation of Enantioenriched Aziridines. Chem. Eur. J., 17: 286–296. doi: 10.1002/chem.201002172
- Issue published online: 5 JAN 2011
- Article first published online: 12 NOV 2010
- Manuscript Received: 29 JUL 2010
- University of Bari
- Interuniversities Consortium C.I.N.M.P.I.S.
- asymmetric synthesis;
- molecular dynamics;
A highly stereo- and regioselective functionalisation of chiral non-racemic aziridines is reported. By starting from a parent enantioenriched aziridine and finely tuning the reaction conditions, it is possible to address the regio- and stereoselectivity of the lithiation/electrophile trapping sequence, thereby allowing the preparation of highly enantioenriched functionalised aziridines. From chiral N-alkyl trans-2,3-diphenylaziridines (S,S)-1 a,b, two differently configured chiral aziridinyllithiums could be generated (trans-1 a,b-Li in toluene and cis-1 a,b-Li in THF), thus disclosing a solvent-dependent reactivity that is useful for the synthesis of chiral tri-substituted aziridines with different stereochemistry. In contrast, chiral aziridine (S,S)-1 c showed a temperature-dependent reactivity to give chiral ortho-lithiated aziridine 1 c-ortho-Li at −78 °C and α-lithiated aziridine 1 c-α-Li at 0 °C. Both lithiated intermediates react with electrophiles to give enantioenriched ortho- and α-functionalised aziridines. The reaction of all the lithiated aziridines with carbonyl compounds furnished useful chiral hydroxyalkylated derivatives, the stereochemistry of which was ascertained by X-ray and NMR spectroscopic analysis. The usefulness of chiral non-racemic functionalised aziridines has been demonstrated by reductive ring-opening reactions furnishing chiral amines that bear quaternary stereogenic centres and chiral 1,2-, 1,3- and 1,5-aminoalcohols. It is remarkable that the solvent-dependent reactivity observed with (S,S)-1 a,b permits the preparation of both the enantiomers of amines (11 and ent-11) and 1,2-aminoalcohols (13 and ent-13) starting from the same parent aziridine. Interestingly, for the first time, a configurationally stable chiral α-lithiated aziridine (1 c-α-Li) has been generated at 0 °C. In addition, ortho-hydroxyalkylated aziridines have been easily converted into chiral aminoalkyl phthalans, which are useful building blocks in medicinal chemistry.