A very efficient enzymatic two-step cascade reaction was devised (E > 200) for the resolution of activated γ-lactams (±)-1 and (±)-2. The N-hydroxymethyl group worked as a traceless activating group, when the reactions were performed with H2O (0.5 equiv) in the presence of benzylamine (1 equiv) in i-Pr2O at 60 °C. The ring-opened enantiomerically pure γ-amino acids (1S,4R)-6 (ee = 99%, intermediate of abacavir) and (1S,3R)-8 (ee = 99%) and unreacted lactams (1S,4R)-1 and (1R,4S)-2 (ee ⩾ 96%) were obtained in good yields (⩾43%). Treatment of (1S,4R)-1 and (1R,4S)-2 with 18% HCl or NH4OH resulted in (1R,4S)-6·HCl and (1S,3R)-8·HCl or (1S,4R)-3 and (1R,4S)-4 quantitatively, with ee ⩾ 96%.
ASJC Scopus subject areas
- Organic Chemistry
- Inorganic Chemistry
- Physical and Theoretical Chemistry