Atropoenantioselective Redox‐Neutral Amination of Biaryl Compounds through Borrowing Hydrogen and Dynamic Kinetic Resolution

Abstract

We report herein a novel atropoenantioselective redox-neutral amination of biaryl compounds triggered by a cascade of borrowing hydrogen and dynamic kinetic resolution under the cooperative catalysis of a chiral iridium complex and an achiral Brønsted acid. This protocol features broad substrate scope and good functional-group tolerance, and allows the rapid assembly of axially chiral biaryl compounds in good to high yields and with high to excellent enantioselectivity.

Dynamic Kinetic Resolution of Heterobiaryl Ketones by Zinc‐Catalyzed Asymmetric Hydrosilylation

“…The imine group in the open form can be then reduced by an asymmetric transfer‐hydrogenation (ATH) reaction. Conversely, this racemization strategy has been recently combined with borrowing‐hydrogen catalysis for a redox‐neutral amination of biaryl compounds . Clayden and Turner have also reported a biocatalytic DKR of atropoisomeric biaryl N ‐oxide aldehydes triggered by a ketoreductase enzyme (Scheme C) .…”

Control of Absolute Stereochemistry in Transition‐Metal‐Catalysed Hydrogen‐Borrowing Reactions

“…It is also possible to employ asymmetric hydrogen-borrowing catalysis to controla na djacent axis of chirality.F or example, Zhang and Wang have reportedah ighly atropselective amination of biaryl alcohols 87 (Scheme 22). [32] This reactioni s mediated by ac hiral iridium(III) catalysti nc onjunction with an achiral Brønsted acid. The reactioni sp roposed to proceed via iridium-mediated oxidation of the racemic biaryl alcohol to the correspondinga ldehyde 91,w hich then condenses with the amine to form imine 92.T his intermediate can undergo reversible cyclizationt of rom cyclic hemiaminal 93,w hich is expected to have al ow barrier to biaryl rotation due to the "bridged biaryl" effect discovered by Bringmann.…”

“…It is also possible to employ asymmetric hydrogen‐borrowing catalysis to control an adjacent axis of chirality. For example, Zhang and Wang have reported a highly atropselective amination of biaryl alcohols 87 (Scheme ) . This reaction is mediated by a chiral iridium(III) catalyst in conjunction with an achiral Brønsted acid.…”

Enantioselective Access to Axial Biaryls via Ruthenium‐Catalyzed Hydrogen‐Transfer Reductive Amination

“…The bridged biaryl lactone system uncovered by Bringmann and co‐workers and propelled by the groups of Wang and Yamada has proven to be an important tool to build the axial chirality . Shortly after, the bridged biaryl lactone system was renewed into biaryl aza ‐lactol by Akiyama and our group to realize the assembly of biaryl compounds. More recently, our group further applied this ingenious strategy to atropoenantioselectively synthesize axial chiral biaryl alkyl amine‐alcohols in good yields with excellent enantioselectivities.…”