A nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides has been developed. Various substituted trifluoromethyl alkenes and epoxides were found to be suitable reaction substrates. This reaction enabled C(sp3)-C(sp3) bond construction through allylic defluorinative cross-coupling of trifluoromethyl alkenes under mild reaction conditions. This methodology was highly compatible with various sensitive functional groups, providing access to a diverse array of functionalized gem-difluoroalkene-containing alcohol compounds.
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http://dx.doi.org/10.1039/d0ob00535e | DOI Listing |
Org Lett
December 2024
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi 563003, China.
We report an efficient, metal-free method for late-stage rapid [F]trifluoromethyl radiolabeling of terminal alkenes at room temperature. Utilizing 3,3-difluoroallyl sulfonium salts as precursors, the process achieves high radiochemical yields (up to 94 ± 2%) in just 30 s, with excellent functional group tolerance. This method offers a simplified and efficient pathway to produce [F]trifluoromethylated terminal alkene compounds, enabling their application in PET imaging and expanding the chemical space for drug discovery.
View Article and Find Full Text PDFOrg Lett
December 2024
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
Herein, we report the rhodium-catalyzed -alkenyl transfer from tertiary allylic alcohols to aryl trifluoromethyl ketones, which provided an efficient way of preparation of trifluoromethyl-containing -allylic alcohols via β--alkenyl elimination. The key -alkenyl-rhodium species were generated with a high degree of stereochemical retention. This reaction featured a broad substrate scope and good functional tolerance and would offer a fascinating approach for the synthesis of -alkenes.
View Article and Find Full Text PDFACS Omega
December 2024
New Drug Development Center (NDDC), Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu 41061, Republic of Korea.
A mild and general method for photoredox-catalyzed trifluoromethylative and pentafluoroethylative heterofunctionalization of alkenes is proposed. In this reaction, the Togni reagent serves as a CF- or CFCF-radical source for the regioselective formation of the C-CF and C-CFCF bonds from alkenes, and additional nucleophiles (O, S, N) provide C-O, C-S, and C-N bonds, respectively. These reactions provide a common gateway to access the fluoroalkylative heterofunctionalization of alkenes.
View Article and Find Full Text PDFJ Org Chem
December 2024
Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan 430205, P. R. China.
We report, for the first time, a visible-light-promoted Markovnikov hydroalkoxylation of α-trifluoromethyl alkenes with 1,2-diketones. This transformation proceeded smoothly in the presence of a tertiary amine (EtN), providing a series of enol ethers containing the trifluoromethylated tetrasubstituted center in moderate to excellent yields. In this protocol, hydrogen atom transfer between this amine and 1,2-diketone substrate affords a ketyl radical and an α-aminoalkyl radical, which engages in the formation of a radical anion of the α-CF alkene via a single electron transfer.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemistry, Johns Hopkins University; Baltimore, Maryland 21218, United States.
The trifluoromethyl (-CF) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made in the development of synthetic methods for trifluoromethylation. In contrast, there are currently no metalloenzymes known to catalyze the formation of C(sp)-CF bonds.
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