Photoenzymatic Enantioselective Intermolecular Radical Hydroamination

Zhang, Z., Feng, J., Yang, C., Cui, H., Harrison, W., Zhong, D., Wang, B., Zhao, H. July 31, 2023. “Photoenzymatic Enantioselective Intermolecular Radical Hydroamination.” Nature Catalysis. DOI: 10.1038/s41929-023-00994-5.

Since the discovery of Hofmann–Löffler–Freytag reaction more than 130 years ago, both the structure and reactivity of nitrogen-centred radicals have been widely studied. Nevertheless, catalytic enantioselective intermolecular radical hydroamination remains a challenge due to the existence of side reactions, the short lifetime of nitrogen-centred radicals and lack of understanding of the fundamental catalytic steps. In the laboratory, nitrogen-centred radicals are produced with radical initiators, photocatalysts or electrocatalysts. In contrast, their generation and reaction are unknown in nature. Here we report a pure biocatalytic system for the photoenzymatic production of nitrogen-centred radicals and enantioselective intermolecular radical hydroaminations by successfully repurposing an ene-reductase through directed evolution. These reactions progress efficiently at room temperature under visible light without any external photocatalysts and exhibit excellent enantioselectivities. A detailed mechanistic study reveals that the enantioselectivity originates from the radical-addition step while the reactivity originates from the ultrafast photoinduced electron transfer from reduced flavin mononucleotide to nitrogen-containing substrates.

Download (35.5 KB) includes:

• Condition optimization
• Control experiments
• Reaction outcomes