Thallium(III) nitrate-mediated efficient synthesis of 2-arylpropionic acids from 1-halogenoethyl aryl ketones

Abstract

Treatment of 1-halogenoethyl aryl ketones [4′-RC₆H₄COCH(X)Me](1; R = H, Buⁱ, OMe, Me, Ph, or Br; X = Br or Cl) with Tl(NO₃)₃·3H₂O and perchloric acid in a trialkyl orthoformate at 25–50 °C affords alkyl esters (3) of 2-arylpropionic acid in good-to-excellent yields via 1,2-aryl migration in substrates (1). The hydrolysis of esters (3) leads to the corresponding acids, some of which are pharmaceutically important compounds. The reaction hardly occurs in methanol. The key step of the reaction is the in situ acetal formation of the starting ketone. The thallium(III) salt acts as an effective Lewis acid catalyst for both acetal formation and halide abstraction.