Gold-catalyzed intramolecular animation of alcohol pro-electrophiles as novel synthetic strategies to nitrogen heterocycles.
Date of Issue2011
School of Physical and Mathematical Sciences
The work of this thesis has been directed towards establishing gold-catalyzed intramolecular amination of alcohol pro-electrophiles as novel synthetic strategies to nitrogen heterocycles. This thesis is divided into three parts: Part I consists of Chapter I, which gives an introduction to gold catalysis and its application to amination of alcohol pro-electrophiles by a variety of nitrogen nucleophiles. Part II is aimed at exploring novel intramolecular-based approaches for N-heterocycles employing the highly reactive and chemoselective nature of gold catalysis in combination with alcohol pro-electrophiles containing a tethered nitrogen moiety. Chapter II addressed an efficient gold-catalyzed synthetic route to 1,2-dihydroquinolines based on intramolecular amination of 1-(2-tosylaminophenyl)prop-2-en-1-ols. The method was shown to be applicable to the synthesis of the bioactive tetrahydroquinoline alkaloid (±)-angustureine. In Chapter III is described, a novel strategy to indenyl-fused and 2,3-disubstituted indoles that relied on a gold-catalyzed cycloisomerization reactions of 1-(2-tosylaminophenyl)prop-2-yn-1-ols. Chapter IV detailed the extension of this approach to include the synthesis of indole-2-carbaldehydes via 1,3-allylic alcohol isomerization (1,3-AAI) of (E)-2-iodomethylene-3-phenyl-1-tosylindolin-3-ols generated in situ from reactions of 1-(2-tosylaminophenyl)prop-2-yn-1-ols with NIS in the presence of a gold catalyst. In Chapter V, gold-catalyzed tandem ring opening/amination of secondary and tertiary 2-tosylaminophenylcyclopropyl carbinols is introduced as an efficient synthetic route to 2,3-dihydro-1H-benzo[b]azepines as well as 2-vinylindolines. Part III contains experimental data (Chapter VII) and references (Chapter VIII) pertaining to this thesis.