Asymmetric C-Alkylation of Nitroalkanes via Enzymatic Photoredox Catalysis
| Autor: | Haigen Fu, Tianzhang Qiao, Jose M. Carceller, Samantha N. MacMillan, Todd K. Hyster |
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| Rok vydání: | 2023 |
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| Zdroj: | Journal of the American Chemical Society. |
| ISSN: | 1520-5126 |
| Popis: | 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. This work was supported by the NIH National Institute of General Medical Sciences (R01GM127703). This work made use of the Cornell University NMR Facility, which is supported, in part, by the NSF through MRI award CHE-1531632. J.M.C. acknowledges the Margarita Salas grant from the Ministerio de Universidades, Universitat Politécnica de Valencia, Spain, funded by the European Union-Next Generation EU (2021-2023). The authors thank Yucong Zheng for his assistance with docking. |
| Databáze: | OpenAIRE |
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