RESUMEN
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 CF2H-imidoyl radical intermediates. The presence of difluoromethyl radicals was experimentally confirmed, and the reaction mechanisms including imidoyl radical and prompt cyclization reactions could be supported theoretically. Furthermore, we obtained valuable information about the imidoyl radical intermediate by performing transverse-field muon spin rotation (TF-µSR) measurements of 2-isocyano-4'-methoxy-1,1'-biphenyl and using density functional theory (DFT) calculations to interpret the spectra. Muonium, a simple free radical, preferentially adds to the carbon atom of the isonitrile unit, yielding the corresponding imidoyl radical. The temperature dependence of the muon hyperfine coupling constant and the spin relaxation of the muoniated radical signal are compatible with the intramolecular cyclization of biaryl-substituted imidoyl radicals on the µs time scale.
RESUMEN
Optically active cyclopropanes have been widely investigated especially from the views of pharmaceutical and agrochemical industries, and substituting one of the methylenes with the difluoromethylene unit should be promising for developing novel biologically relevant compounds and functional materials. In this paper, the copper-catalyzed enantioselective hydrosilylation of gem-difluorocyclopropenes to provide the corresponding chiral gem-difluorocyclopropanes is presented. The use of copper(I) chloride, chiral ligands including bidentate BINAPs and monodentate phosphoramidites, and silylborane Me2 PhSi-Bpin accompanying sodium tert-butoxide in methanol was appropriate for the enantioselective hydrosilylation of the strained C=C double bond, and the resultant chiral difluorinated three-membered ring was unambiguously characterized. Subsequent activation of the silyl groups in enantio-enriched gem-difluorocyclopropanes showed substantial reduction of the enantiopurity, indicating cleavage of the distal C-C bond leading to the transient acyclic intermediates.