Bronsted Acid Catalyzed Alkylation of Indoles with Tertiary Propargylic Alcohols: Scope and Limitations

Direct alkylation of indoles with a wide variety of tertiary propargylic alcohols under Bronsted acid catalysis conditions has been studied. A general and environmentally friendly method for the synthesis of 3-propargylated indoles with quaternary carbon atoms at their propargylic positions has been developed. The reactions are highly regioselective with regard both to the indole and to the alkynol components. Only with N-unsubstituted 2-arylindoles do competitive S-N' reactions take place to afford 3-dienyl- or 3-allenylindoles, depending on the alkynol moiety. The reactions were carried out in air with undried solvents, and water was the only side product.