Asymmetric Nucleophilic Acylation with Metalated Amino Nitriles: Diastereo- and Enantioselective Synthesis of 2-Substituted 3-Aroylcyclohexanones via Tandem Michael Addition/α-Alkylation

Abstract

Tandem conjugate addition/α-alkylation of lithiated chiral α-amino nitriles 3 and alkyl bromides to 2-cyclohexenone afforded 2-substituted 3-aroylcyclohexanones 5 of high diastereo- and enantiomeric purity (de ≥98%, ee ≥97-≥99%) and in good overall yields. The absolute configuration of the new stereogenic centres was determined by X-ray structure analysis of the Michael adduct 4c.