A highly stereo- and regioselective functionalisation of chiral nonracemic 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)-1a,b, two differently configured chiral aziridinyllithiums could be generated (trans- 1a,b-Li in toluene and cis-1a,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)-1c showed a temperature-dependent reactivity to give chiral ortho-lithiated aziridine 1c-ortho-Li at 78 8C and a-lithiated aziridine 1c-a-Li at 0 8C. Both lithiated intermediates react with electrophiles to give enantioenriched ortho- and a-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)-1a,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 a-lithiated aziridine (1c-a-Li) has been generated at 0 8C. In addition, ortho-hydroxyalkylated aziridines have been easily converted into chiral aminoalkyl phthalans, which are useful building blocks in medicinal chemistry.
Solvent- and Temperature-Dependent Functionalization of Enantioenriched Aziridines
LUISI, Renzo
2011-01-01
Abstract
A highly stereo- and regioselective functionalisation of chiral nonracemic 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)-1a,b, two differently configured chiral aziridinyllithiums could be generated (trans- 1a,b-Li in toluene and cis-1a,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)-1c showed a temperature-dependent reactivity to give chiral ortho-lithiated aziridine 1c-ortho-Li at 78 8C and a-lithiated aziridine 1c-a-Li at 0 8C. Both lithiated intermediates react with electrophiles to give enantioenriched ortho- and a-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)-1a,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 a-lithiated aziridine (1c-a-Li) has been generated at 0 8C. In addition, ortho-hydroxyalkylated aziridines have been easily converted into chiral aminoalkyl phthalans, which are useful building blocks in medicinal chemistry.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
