Diethoxymethyl protected pyrroles: Synthesis and regioselective transformations

Treatment of the acceptor-substituted pyrroles la-k with neat triethyl orthoformate gives access to the diethoxymethyl (DEM) protected derivatives 2a-k in high yield. Convenient and mild cleavage was achieved by subsequent treatment of the DEMpyrroles 2a-k with trifuoroacetic acid in acetonitrile and aqueous NaOH at room temperature, DEM protection proved suitable for a variety of regioselective transformations involving directed orthometalation and iodine-magnesium exchange processes, Furthermore, electrophilic halogenations and Pd-catalyzed coupling reactions were also carried out.