Chemists have achieved various transformations by using visible light activation of organic compounds, changing the traditional reaction path and promoting the development of new catalytic models. Now, some researchers envisage whether a suitable redox system can be determined to overcome the electronic characteristics of the precursor of aryl radicals and drive the formation of colored EDA complexes, so as to realize the widely applicable aryl radical generation process. Recently, they have formed a blue-light absorption EDA complex with the newly designed triarylamine donor and the in-situ generated sulfonium salt as the electron acceptor, which can promote the formation of aryl radicals through photoactivation. Subsequently, the site-selective C-H bond alkylation and cyanidation of aromatics were successfully realized using this process under the metal-free catalysis, and good results were also achieved in the synthesis and post-modification of drug molecules and agricultural chemicals.
Figure 1. Photoactivated EDA complex drives the C-H bond functionalization of aromatics.
First, the researchers selected 4-tert-butylphenyldibenzothiophene sulfide and enol silyl ether as template substrates to screen different triarylamine donors. After further optimizing the reaction solvent and the wavelength of light, it was found that 1,2-DE was the best solvent. Subsequently, the researcher realized the one-pot series reaction of direct C-H alkylation of tert-butylbenzene, and then added enol silyl ether and donor to the system and irradiated with blue LEDs, which can be obtained with 57% yield α- Aromatization products.
Under the optimal conditions, the researchers investigated the range of substrates for the one-pot series reaction of C-H bond alkylation. The results showed that when 4-fluorophenyl substituted enol silyl ether was used as the coupling agent, benzene, alkyl/aryl substituted aromatics, aryl sulfonamide, aryl ester, anisole derivatives, trifluoromethylbenzene sulfide, and even (±) - ibuprofen methyl ester and benzofuran were compatible with the reaction, and the corresponding products were obtained with good yields. Secondly, the researchers explored different types of enol silyl ether with (4-methoxy-3-(methoxycarbonyl) phenyl) dibenzothiophene sulfide as the standard substrate. The results showed that enol silyl ether with different substituents could be effectively converted into the desired products, and the scheme also had good regioselectivity.
Subsequently, researchers hope to use this aryl radical formation strategy to realize other C-H bond functionalization. Since tert-butyl isonitrile can be added by aryl radical to form aryl nitrile, researchers try to realize the C-H bond cyanation reaction of aromatics through photoactivation of EDA complex, and also obtain corresponding products. Under the optimal conditions, the researchers also successfully realized the one-pot series reaction of direct C-H bond cyanidation of aromatics.
Next, the researchers confirmed that the two C-H bond functionalization mediated by this new photo-activated EDA complex has potential application value in the synthesis and post-modification of natural products and complex molecules, such as: 1) the bactericide acetaminophen, the hormone estrone, the non-steroidal anti-inflammatory drug naproxen, the drug for hyperlipidemia, and the anti-arrhythmia drug mexiletine can be compatible with this reaction; 2) It can also realize de novo synthesis of drug targets, and can synthesize febuxostat, a drug for treating gout and hyperuricemia, after three steps of transformation.
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Reference
- A general arene C–H functionalization strategy via electron donor–acceptor complex photoactivation
Abhishek Dewanji, Leendert van Dalsen, James A. Rossi-Ashton, Eloise Gasson, Giacomo E. M. Crisenza, David J. Procter
