We describe a novel reagent system to obtain acyl fluorides directly from three different functional group precursors: carboxylic acids, aldehydes, or alcohols. The transformation is achieved via a combination of trichloroisocyanuric acid and cesium fluoride, which facilitates the synthesis of various acyl fluorides in high yield (up to 99%). It can be applied to the late-stage functionalization of natural products and drug molecules that contain a carboxylic acid, an aldehyde, or an alcohol group.
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http://dx.doi.org/10.1021/acs.orglett.0c04087 | DOI Listing |
Arch Biochem Biophys
January 2025
Department of Biosciences Grand Asian University of Sialkot, Pakistan.
Acyl thiourea scaffolds are frequently employed in drug development to discern unique and essential therapies for the eradication of the most challenging diseases. Hence, we developed a library of novel cyclopropyl incorporating acyl thiourea derivatives (4a-j) and evaluated their antimicrobial, α-amylase, and proteinase K inhibition potential. Compound (4h) (4-methoxy) demonstrated the strongest α-amylase inhibition (IC = 1.
View Article and Find Full Text PDFChemistry
December 2024
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, P. R. China.
Trifluoromethylarenes (ArCF) are crucial bioisosteres in medicinal chemistry, but catalyst-free and controlled photo-activation of the ArC(sp)-F bond remains a significant challenge. The photo-induced defluorination acyl fluoride exchange (photo-DAFEx) of m-trifluoromethylaniline, induced by ultraviolet light, emerges as a promising novel photo-click reaction for photoaffinity drug discovery. However, the photophysical properties of NMePhFC(sp)-F derivatives and factors affecting ArC(sp)-F bond activation in photo-DAFEx are not yet fully understood, hindering the development of new photo-defluorination reagents with longer absorption wavelength for the photo-DAFEx.
View Article and Find Full Text PDFAcc Chem Res
November 2024
State Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China.
Org Biomol Chem
December 2024
Continuous Flow Engineering Laboratory of National Petroleum and Chemical Industry, Changzhou University, Changzhou, Jiangsu 213164, China.
We report an efficient photocatalytic protocol for the defluorocyanoalkylation and defluoroacylation of α-trifluoromethyl styrenes by utilizing oxime esters as radical donors, allowing for the preparation of diverse -difluoroalkenes. The treatment of α-trifluoromethyl styrenes with cyclobutanone oxime esters led to the formation of distal cyano group-anchored -difluoroalkenes. Notably, adding KCO as an inorganic base to the photocatalytic system afforded γ,γ-difluoroallylic ketones by utilizing acyl oxime esters as the acylating agents.
View Article and Find Full Text PDFOrg Lett
November 2024
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
A metal-free and mild cleavage of tertiary -methoxybenzyl amides (PMB -amide) under photoredox conditions is developed using Mes-Acr-PhBF and Selectfluor to activate the electron-rich benzylic C-H bond of the PMB moiety. The resulting acyl fluoride intermediate is versatile and facilitates a one-pot transamidation of the PMB -amide. The value of this protocol is highlighted by performing the chemoselective activation of the PMB -amide in bifunctional molecules containing more reactive functionalities than the amide.
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