HFIP mediated oxime ether synthesis: a metal, base and additive free approach†

Abstract

Oxime ethers are extensively present as key components in numerous active pharmaceutical ingredients and many other synthetically viable organic compounds. Herein, we present a metal, base and additive free mild C–O bond formation strategy for the synthesis of oxime ethers from various oxime derivatives and tertiary and secondary aryl alcohols. The reaction is carried out in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as the green solvent at 30 °C. The reaction tolerates both aldoximes and ketoximes including ketoximes bearing heteroatoms, furnishing high yields (up to 99%). The formation of a triphenylmethyl carbocation as an intermediate is supported via UV-Vis spectroscopy. Successful gram-scale synthesis of the oxime ether, low energy input and simple reaction conditions further highlight the potential of this reaction to effectively transition from the laboratory scale to industrial production. A broad substrate scope compatibility was also observed.