Nickel-Catalyzed Enantioconvergent Allenylic Amination of Allenols Activated by Hydrogen-Bonding Interaction with Methanol.

Abstract

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.