Studies on diastereoselective additions of methoxyallene to chiral hydrazones

Abstract

The new chiral auxiliaries for the asymmetric reactions were synthesized from (S)-indoline-2-carboxylic acid. The reaction of α -lithiomethoxyallene with chiral hydrazones derived from (S)-indoline afforded the chiral hydrazines with high diastereoselectivities (up to >99% de). When the reactions were carried out at -78℃ in THF, a reaction mechanism was proposed which involves intramolecular or intermolecular electron transfers from the lithium amide leading to hydrazinyl radicals. The relative stabilities of these intermediates could be explained by the role of the substituents of the terminal nitrogen. The conjugate addition of lithiated dibenzylamine to α,β -unsaturated amides drived from (S)-indoline derivatives proceeded rapidly to the expected products in extremely high diastereoselectivities. The hydrolysis of amides gave chiral β-amino acids with high enantiomeric excess up to >98% ee.