Synthesis and stability of 2-(1,1-difluoroalkyl) thiophenes and related 1,1-difluoroalkyl benzenes: fluorinated building blocks for liquid crystal synthesis

The synthesis of a series of 2-(1,1-difluoroalkyl) thiophenes, including some biphenylthienyl liquid crystalline materials, was examined using a variety of fluorination approaches. For comparison purposes, a series of 1,1-difluoroalkyl benzene analogs were also prepared. The direct fluorodeoxygenation of alkyl thienyl ketones and alkyl phenyl ketones using various aminofluorosulfuranes proceeded in only moderate to poor yields. In contrast, fluorodesulfurization of the corresponding 1,3-dithiolanes using NOBF4/PPHF cleanly afforded the desired 2-(1,1-difluoroalkyl) thiophenes (and analogous 1,1-difluoroalkyl benzenes) in high yields. Fluorodesulfurization of 2-alkyl-2-thienyl-1,3-dithiolanes using NBS (or DBH)/PPHF was complicated by competing ring and/or side chain bromination pathways. These problems were avoided when using NIS/PPHF. Although the various 1,1-difluoroalkyl arene products were sensitive to hydrolytic decomposition on prolonged exposure to silica, the purified products proved quite stable and were well suited for use as building blocks for liquid crystal synthesis.