A Visible Light Promoted Regioselective Cascade Radical Trifluoromethylation/Cyclization of <i>N</i>-Isopentenyl Aldehyde Hydrazones: Access to Trifluoromethylated Tetrahydropyridazine Derivatives
Yuanyuan Ren, Yuxiu Zhou, Ke‐Hu Wang, Junjiao Wang, Danfeng Huang, Yulai Hu
Abstract
N -Isopentenyl aldehyde hydrazones was served as novel precursor to access tetrahydropyridazine derivatives. Under visible-light irradiation, various trifluoromethyl tetrahydropyridazines were synthesized (up to 86% yield) by using cost-effective and industrially available CF 3 Br as the trifluoromethyl radical source. A distinct advantage of this process is the regioselective incorporation of trifluoromethyl group into the ring of tetrahydropyridazines. Additionally, trifluoroethyl tetrahydropyridazines and trifluoroethyl dihydropyrazoles could also be generated from N -allyl or homoallyl aldehyde hydrazones under the same conditions. This method demonstrates a broad scope of substrates and excellent functional group tolerance, offering a practical strategy to synthesize pharmaceutically valuable CF 3 /CF 3 CH 2 -containing tetrahydropyridazines. Furthermore, the reaction mechanism is proposed on the basis of control experiments and density functional theory (DFT) calculations.