A highly efficient approach of visible-light-driven radical difluoromethylation of isocyanides to access a wide variety of difluoromethylated phenanthridines and isoquinolines is herein described. Electrophilic -(difluoromethyl)diarylsulfonium salt proved to be a good difluoromethyl radical precursor under photoredox catalysis. A broad range of isocyanides were tolerated to furnish the corresponding difluoromethylated phenanthridines, isoquinolines, furo[3,2-]pyridine, and pyrido[3,4-]indole in moderate to excellent yields under mild conditions. A plausible mechanism was also proposed.
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http://dx.doi.org/10.1021/acs.joc.0c00816 | DOI Listing |
Org Lett
July 2023
Advanced Research Institute and School of Pharmaceutical Sciences, Taizhou University, Jiaojiang, Zhejiang 318000, P. R. China.
A multicomponent dearomative difluoroalkylation of isoquinolines has been developed with difluorinated silyl enol ethers serving as poor nucleophiles without an additional transition-metal or organic catalyst. The sequential oxidative rearomatization under different alkaline conditions provides a controllable formal C-H difluoroalkylation and difluoromethylation method for isoquinolines without peroxide or metal oxidant. A series of isoquinolines including a pharmaceutical, phenanthridine, quinolines, and difluorinated silyl enol ethers were suitable substrates to construct -difluorinated heterocycles.
View Article and Find Full Text PDFJ Org Chem
July 2023
Department of Applied Chemistry, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1-H-113 Ookayama, Meguro-ku, Tokyo 152-8552, Japan.
The 6-(difluoromethyl)phenanthridine unit is a highly attractive fluoroalkyl-substituted planar nitrogen heterocycle in pharmaceutical and agrochemical research. In this paper, we report that difluoromethylborates can be used as a source of difluoromethyl radicals for isonitrile insertion, leading to 6-(difluoromethyl)phenanthridines. Tuning the aryl substituents in the difluoromethylborates and oxidizing reagents enabled the synthesis of 6-(difluoromethyl)phenanthridines through the generation of difluoromethyl radical and spontaneous intramolecular cyclization of the CFH-imidoyl radical intermediates.
View Article and Find Full Text PDFJ Org Chem
August 2020
School of Pharmaceutical Sciences, Shenzhen University Health Science Centre, Shenzhen University, 3688 Nanhai Avenue, Shenzhen 518060, China.
A highly efficient approach of visible-light-driven radical difluoromethylation of isocyanides to access a wide variety of difluoromethylated phenanthridines and isoquinolines is herein described. Electrophilic -(difluoromethyl)diarylsulfonium salt proved to be a good difluoromethyl radical precursor under photoredox catalysis. A broad range of isocyanides were tolerated to furnish the corresponding difluoromethylated phenanthridines, isoquinolines, furo[3,2-]pyridine, and pyrido[3,4-]indole in moderate to excellent yields under mild conditions.
View Article and Find Full Text PDFJ Org Chem
July 2019
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry , University of Chinese Academy of Sciences, Chinese Academy of Sciences , 345 Ling-Ling Road , Shanghai 200032 , China.
The fluoroalkylation of various nucleophilic reagents with (phenylsulfonyl)difluoromethyl (PhSOCF)-substituted phenanthridines was achieved to give fluorinated phenanthridine derivatives, which enables the construction of both carbon-heteroatom and carbon-carbon bonds via the substitution of the phenylsulfonyl group. Mechanistic studies indicated that these reactions proceed through a unimolecular radical nucleophilic substitution (S1) mechanism. It is worthwhile noting that in the cases of O-nucleophiles ( t-BuO and PhO), the addition of t-BuOK/PhCHO could significantly promote the reactions, due to the in situ formation of a highly reactive electron donor species through the interaction of t-BuOK, PhCHO, and the solvent DMF, which can effectively initiate the single electron transfer process.
View Article and Find Full Text PDFChem Commun (Camb)
October 2017
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China.
A silver-mediated oxidative difluoromethylation of phenanthridines and 1,10-phenanthrolines with TMSCFH is disclosed. This C-H difluoromethylation of N-containing polycyclic aromatics constitutes an efficient method for the regioselective synthesis of difluoromethylated N-heterocycles.
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