Synthesis of Chiral a-Amino Ketones via Transition Metal Catalyzed or Photoredox Cross-Coupling and Olefin Photo-Cleavage Reaction Sequence

We report a convenient two-step approach to a-amino ketones involving cross-coupling and oxidative cleavage sequence. The cross-coupling reaction creates a divergent functionalization of the molecular platform, e.g., N-(2-bromoallyl)amine, whereas the oxidative cleavage establishes the carbonyl functionality. This strategy allows for an introduction of aryl/heteroaryl and alkyl groups, either through the Suzuki reaction with arylboronic acids or via dual photoredox/Ni-catalysis to install alkyl groups. The oxidative cleavage to provide target a-amino ketones can be realized either by treating with ozone or by employing milder photochemical protocols involving oxygen or photoexcited nitroarenes as oxidants. We successfully demonstrate the scalability of this protocol, which, together with its simplicity, generality, and its ability to provide access to amino ketones that are inaccessible through other strategies, highlights the suitability of this approach for a wide range of applications across the different chemical sciences.

Automated summary

We present a convenient two-step method for the synthesis of α-amino ketones through cross-coupling and oxidative cleavage sequence. The cross-coupling reaction enables the functionalization of the molecular platform with aryl/heteroaryl and alkyl groups, while the oxidative cleavage establishes the carbonyl functionality. This strategy offers a versatile approach to access a wide range of α-amino ketones that are not accessible by other methods, making it suitable for various applications in different chemical sciences.