Selective C-H Halogenation of Alkenes and Alkynes Using Flavin-Dependent Halogenases.
Yuhua Jiang1, Ahram Kim1, Cahmlo Olive1
1Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Angewandte Chemie (International Ed. in English)
|January 27, 2024
Summary
Single component flavin-dependent halogenases (FDHs) can now halogenate alkenes and alkynes. This discovery expands biocatalysis applications for creating valuable halogenated compounds.
Area of Science:
- Biocatalysis
- Enzymology
- Organic Chemistry
Background:
- Single component flavin-dependent halogenases (FDHs) integrate flavin reductase and halogenase activities.
- Previously, AetF demonstrated site-selective halogenation of aromatics and enantioselective reactions on styrenes.
Purpose of the Study:
- To investigate the potential of AetF as a catalyst for C-H halogenation of alkenes and alkynes.
- To explore the scope and selectivity of FDH-catalyzed halogenation for these substrate classes.
Main Methods:
- Enzymatic assays using AetF and its homologues with various alkene and alkyne substrates.
- Stereoselectivity analysis of halogenated products.
- Mutagenesis studies and deuterium kinetic isotope effect measurements to elucidate the reaction mechanism.
Main Results:
- AetF effectively catalyzes the halogenation of 1,1-disubstituted styrenes with high stereoselectivity.
- AetF and related enzymes were shown to halogenate terminal alkynes.
- Mechanistic studies support a covalent catalysis pathway for alkyne halogenation.
Conclusions:
- This study broadens the substrate scope of flavin-dependent halogenase catalysis.
- Single component FDHs offer unique and valuable biocatalytic routes for synthesizing halogenated alkenes and alkynes.
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