Indium(iii)-catalysed cycloisomerization reactions of o-(hydroxyalkynyl)benzyl alcohols and functionalized 1,6-enynes

Abstract

This Doctoral Thesis studies the electrophilic activation of alkynes under indium(III) catalysis to promote cycloisomerization reactions allowing the synthesis of novel carbo- and heterocyclic compounds. The document is organized in three chapters: Chapter I presents a comprehensive overview on the electrophilic activation of alkynes under metal catalysis, particularly in precedents using indium(III) as catalyst; Chapter II is devoted to the synthesis of benzannulated spiroketals from o-(hydroxyalkynyl)benzyl alcohols under indium(III) catalysis. After a general introduction including precedents in metal-catalysed double cyclization of alkyne diols, our results using indium(III) catalysis are presented. Indium triiodide is shown as efficient catalyst for the synthesis of a variety of spiroketals through intramolecular double alkyne hydroalkoxylation with endo regioselectively; Chapter III is focused on tandem cycloisomerization reactions of functionalized 1,6-enyne under indium(III) catalysis. Following an introductory overview of metal-catalysed 1,6-enyne cycloisomerization, we present our studies involving indium(III). The tandem transformation allows the diastereoselective and stereospecific formation of bicyclic structures with 5-exo-dig regioselectivity and high functional group tolerance (alcohol, amine, carboxylic acid or aldehydes). In the same chapter we also describe the tandem intermolecular cycloisomerization-nucleophilic addition of 1,6-enynes. The reaction also proceeds through 5-exo-dig cyclization, followed by the addition of alcohols, carboxylic acids, carbo nucleophiles, and azides.