Efficient method for photocatalytic fluoroalkylations of (hetero)arenes
Fluorinated alkylated aromatic compounds have properties such as permeability, lipophilicity and metabolic stability. Considerable effort has been devoted to the development of efficient methods for incorporating the fluoroalkyl group into aromatic frameworks. However, many commonly used fluoroalkylation reagents are expensive or operationally inconvenient, and some of them require multi-step synthesis.
Recently, a research group led by Prof. Su Weiping of the Fujian Institute of Research on the Structure of Matter of the Chinese Academy of Sciences developed a general photocatalytic method for regioselective CH-fluoroalkylation of (hetero)arenes using readily available fluoroalkylcarboxylic anhydrides as fluoroalkylating reagents in the presence of simple acetoxime as activator.
The study is published in Chem Catalysis on June 16.
The CH-fluoroalkylation method is attributed to the discovery of the acid-mediated reactivity of acetoxime ester to single-electron reduction cleavage of the NO bond.
The researchers evaluated the feasibility of the photocatalytic reduction-activated decarboxylation of acetoxime-trifluoroacetate to generate CF3 radical. They then developed an in-situ activation strategy for photocatalytic trifluoromethylation of (hetero)arenes via in-situ generation of acetoxime trifluoroacetate and TFA from trifluoroacetic anhydride (TFAA) and acetoxime.
The mechanistic studies showed that the interaction between TFA and acetoxime ester resulted in the photoredox-mediated cleavage of NO bond of acetoxime ester to generate trifluoromethylcarboxylic radical and imine. This was opposed to the inherent reactivity of NO bonding of acetoxime ester toward generation of iminyl radical and trifluoroacetate anion under photoredox catalysis, demonstrating unprecedented acid-induced reactivity in acetoxime ester.
The activator acetoxime used in this study is inexpensive, non-toxic, air stable and easy to handle. This combination of acetoxime/fluoroalkyl carboxylic anhydrides has a low cost and high in-situ activation efficiency. It can avoid cumbersome presynthesis and the resulting by-products, 2-propanimine or acetone, are small, volatile and easy to remove.
This study not only provides an efficient approach to the fluoroalkylation of (hetero)arenes and alkenes, but also reveals a novel reactivity mode for photodirected cleavage of σ-NO bonds in oxime esters, which will help to facilitate the synthetic application of readily available oxime. esters.
Trifluoroacetic acid acts as a trifluoromethylating agent in arene-CH functionalization
Min Zhang et al, Photocatalytic fluoroalkylations of (hetero)arenes enabled by the acid-mediated reactivity of acetoxime esters, Chem Catalysis (2022). DOI: 10.116/j.checat.2022.05.018
Quote: Efficient Method for Photocatalytic Fluoroalkylations of (hetero)arenes (2022, June 21) Retrieved June 21, 2022 from https://phys.org/news/2022-06-efficient-method-photocatalytic-fluoroalkylations-heteroarenes.html
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