Fu H,
Qiao T,
Carceller JM,
MacMillan SN,
Hyster TK.
*
Cornell University, Ithaca, USA
Asymmetric
C‑Alkylation of Nitroalkanes
via Enzymatic Photoredox Catalysis.
J. Am. Chem. Soc. 2023;
145: 787-793
DOI:
10.1021/jacs.2c12197
Key words
alkylation - nitronates - nitroalkanes - α-tertiary amines - ‘ene’-reductase (ERED)
- photoredox catalysis
Significance
Hyster and co-workers report a highly stereoselective C-alkylation of secondary nitronates
with alkyl halides catalyzed by an engineered flavin-dependent ‘ene’-reductase (from
Geobacillus kaustophilus, GkOYE-G7) under LED irradiation. The reported method provides straightforward access
to tertiary nitroalkanes with moderate to high yields and generally high enantioselectivity.
The obtained enantioenriched tertiary nitroalkanes can be reduced to the corresponding
α-tertiary amines — important motifs in bioactive molecules and pharmaceuticals.
Comment
The high selectivity and evolvability of enzyme catalysis makes it an attractive solution
for many synthetic challenges related to reactions’ chemo- and stereoselectivity.
Although natural enzymes cannot catalyze the C-alkylation of nitronates with alkyl
halides, the authors demonstrated that this non-natural mode of action can be evoked
by photoirradiation and directed enzyme evolution. Such mechanism combining SET reduction,
controlled radical addition and oxidation of nitro radical anion is enabled by an
enzyme-templated CT complex, which was observed in mechanistic studies.
