Energy-Transfer-Enabled Regioconvergent Alkylation of Azlactones via Photocatalytic Radical-Radical Coupling

C-4-selective functionalization of azlactones pro-vides access to alpha,alpha-disubstituted unnatural alpha-amino acids, which has been extensively investigated in the past decades. However, a vast majority of such transformations are two-electron transfer reactions. Herein, leveraging on the persistent radical effect, we develop photocatalytic energy transfer-enabled regioconvergent alkylation of azlactones with redox-active esters via radical-radical couplings. This strategy is extended to the utilization of simple alkanes as the radical precursors, whereby the aryl redox-active esters play a dual role of an oxidant and a hydrogen-atom-transfer agent. Notably, the excited state Ir(III) photocatalyst enables selective activation of the unwanted imine products through triplet energy transfer, delivering C-4-functionalized azlactones with high regioselectivity. Both experimental investigations and density functional theory calculations on the reaction mechanism were performed, supporting EnT-enabled regioconvergent photocatalytic radical-radical coupling reaction pathways.

Automated summary

The regioconvergent alkylation of azlactones with redox-active esters via radical-radical couplings was developed using photocatalytic energy transfer. This strategy allows the use of simple alkanes as radical precursors, with aryl redox-active esters serving as both oxidants and hydrogen-atom-transfer agents. Excited state Ir(III) photocatalyst enables the selective activation of unwanted imine products, resulting in high regioselectivity of C-4-functionalized azlactones. Experimental investigations and density functional theory calculations support the proposed regioconvergent photocatalytic radical-radical coupling reaction pathways enabled by energy transfer.