Trifluoromethanesulfonic Acid Catalyzed Friedel–Crafts Alkylations of 1,2,4-Trimethoxybenzene with Aldehydes or Benzylic Alcohols

Abstract

Trifluoromethanesulfonic acid in acetonitrile was found to efficiently catalyze Friedel-Crafts alkylations of 1,2,4-trimethoxybenzene with a variety of simple or functionalized aldehydes to provide di- or triarylmethanes in high yields. The operationally simple protocol allowed a short synthesis of the phenylpropanoid natural product (-)-tatarinoid C establishing its absolute configuration. Under the developed reaction conditions a benzylic alcohol instead of an aldehyde also underwent reactions with 1,2,4-trimethoxybenzene and other nucleophiles to afford unsymmetrically substituted compounds.