Asymmetric C-Alkylation of Nitroalkanes via Enzymatic Photoredox Catalysis.
J Am Chem Soc
; 145(2): 787-793, 2023 01 18.
Article
em En
| MEDLINE
| ID: mdl-36608280
ABSTRACT
Tertiary nitroalkanes and the corresponding α-tertiary amines represent important motifs in bioactive molecules and natural products. The C-alkylation of secondary nitroalkanes with electrophiles is a straightforward strategy for constructing tertiary nitroalkanes; however, controlling the stereoselectivity of this type of reaction remains challenging. Here, we report a highly chemo- and stereoselective C-alkylation of nitroalkanes with alkyl halides catalyzed by an engineered flavin-dependent "ene"-reductase (ERED). Directed evolution of the old yellow enzyme from Geobacillus kaustophilus provided a triple mutant, GkOYE-G7, capable of synthesizing tertiary nitroalkanes in high yield and enantioselectivity. Mechanistic studies indicate that the excitation of an enzyme-templated charge-transfer complex formed between the substrates and cofactor is responsible for radical initiation. Moreover, a single-enzyme two-mechanism cascade reaction was developed to prepare tertiary nitroalkanes from simple nitroalkenes, highlighting the potential to use one enzyme for two mechanistically distinct reactions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alcanos
/
Nitrocompostos
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos