Photoinduced Difluoromethylation Cyclization to Generate Medium-Sized Difluoro-benzo[<i>b</i>]azepines
Dongyang Zhao, Xin Wang, Jia-Bo Huang, Tingting Yu, Er‐Jun Hao, Shao‐Fei Ni, Kai Sun
Abstract
Compared with the energetically favorable 5- or 6-membered fluoro-functionalized heterocycles, the construction of medium-sized fluoro-heterocycles is relatively under-researched because of their inherently unfavorable enthalpic and entropic nature. Based on rational design and DFT calculations, a novel photocatalytic difluoromethyl radical-initiated intramolecular 7- endo -trig cyclization was realized, thus affording a sustainable route for the synthesis of challenging fluoro-functionalized medium-sized N -heterocycles. Depending on atomic dipole moment corrected Hirshfeld population (ADCH) charge calculations, the chemoselective 6- exo -trig radical cyclizations were further replenished. Large-scale synthesis and derivatization demonstrated the wide utility of this method.