(482e) Photoenzymatic Asymmetric Hydroamination with Simple Dialkyl Amines

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored for the use of dialkyl amine substrates. Herein we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for the asymmetric intermolecular hydroamination with simple alkyl amines and vinyl arenes. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a longstanding challenge in chemical synthesis.