Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis.
J Am Chem Soc
; 146(15): 10716-10722, 2024 Apr 17.
Article
in En
| MEDLINE
| ID: mdl-38579164
ABSTRACT
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 with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. 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, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.
Full text:
1
Database:
MEDLINE
Language:
En
Journal:
J Am Chem Soc
Year:
2024
Type:
Article
Affiliation country:
United States