Synthesis of C(CF3)Me2 Tetrahydropyridazines and Dihydropyrazoles via Radical Cascade and Mechanistic Studies by DFT Calculations

Abstract

Herein, we report a metal-free radical cascade cyclization initiated by 1,1-dimethyl-2,2,2-trifluoroethyl radicals. Readily available trifluoromethyl-substituted carboxylic acids were used as radical precursors and reacted with N-homoallyl or N-allyl aldehyde hydrazones to afford 1,1-dimethyl-2,2,2-trifluoroethylated tetrahydropyridazine and dihydropyrazole derivatives. Under the optimized conditions, 25 examples were obtained in moderate to good yields. The reaction proceeds without metal catalysts, highlighting its operational simplicity and practical utility in the synthesis of fluorinated nitrogen heterocycles. Density functional theory calculations were performed to elucidate the radical reaction mechanism.