Photoenzymatic enantioselective intermolecular radical hydroamination

Zhengyi Zhang, Jianqiang Feng, Chao Yang, Haiyang Cui, Wesley Harrison, Dongping Zhong, Binju Wang, Huimin Zhao

Research output: Contribution to journalArticlepeer-review


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. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalNature Catalysis
Issue number8
StatePublished - Aug 2023

ASJC Scopus subject areas

  • Catalysis
  • Bioengineering
  • Biochemistry
  • Process Chemistry and Technology


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