title: Solvent- and temperature-dependent functionalisation of enantioenriched aziridines.
abstract: 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.
authors.affiliation: Dipartimento Farmaco Chimico, Università degli Studi di Bari A. Moro, Via E. Orabona, 4 70125 Bari, Italy.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: de Ceglie
authors.forename: Biagia
authors.initials: B
authors.lastname: Musio
authors.forename: Francesco
authors.initials: F
authors.lastname: Affortunato
authors.forename: Anna
authors.initials: A
authors.lastname: Moliterni
authors.forename: Angela
authors.initials: A
authors.lastname: Altomare
authors.forename: Saverio
authors.initials: S
authors.lastname: Florio
authors.forename: Renzo
authors.initials: R
authors.lastname: Luisi
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012997:Solvents; D013237:Stereoisomerism
chemical_list: D000588:Amines; D000605:Amino Alcohols; D001388:Aziridines; D012997:Solvents; D008094:Lithium