α-Fluoronitroalkenes as Fluorinated Building Blocks: Solvent-Controlled Functionalization with Hydrazones

Abstract

While α-fluoronitroalkenes have been widely explored in annulation and cycloaddition chemistry, controlled intermolecular C–N bond formation through conjugate addition remains largely undeveloped. Moreover, solvent-controlled divergence between conjugate addition and cyclization from identical starting materials has not been systematically demonstrated for α-fluoronitroalkenes. Herein, we report a base-mediated 1,4-conjugate addition of hydrazones to α-fluoronitroalkenes under aprotic conditions, affording N-fluoroalkyl hydrazones. In contrast, protic acidic conditions divert reactivity toward 4-fluoropyrazole formation, highlighting a solvent-controlled divergence in reaction pathways. This one-pot protocol tolerates a wide range of aromatic, heteroaromatic, and aliphatic substrates, providing isolable N-fluoroalkyl hydrazones in moderate to high yields. This study expands the synthetic utility of both hydrazones and α-fluoronitroalkenes as building blocks of interest for applications in organic synthesis and medicinal chemistry.