Asymmetric Construction of Alkaloids by Employing a Key ω‐Transaminase Cascade
Freya Taday, James P. Ryan, Stephen P. Argent, Vittorio Caprio, Beatriz Maciá, Elaine O’Reilly
Abstract
An ω-transaminase-triggered intramolecular aza-Michael reaction has been employed for the preparation of cyclic β-enaminones in good yield and excellent enantio- and diastereoselectivity, starting from easily accessible prochiral ketoynones and commercially available enzymes. The powerful thermodynamic driving force associated with the spontaneous aza-Michael reaction effectively displaces the transaminase reaction equilibrium towards product formation, using only two equivalents of isopropylamine. To demonstrate the potential of this methodology, this biocatalytic aza-Michael step was combined with annulation chemistry, affording unique stereo-defined fused alkaloid architectures.