Discovery of New Carbocyclizations Involving Activation of C–C Multiple Bonds by Electrophilic Noble Metals

Abstract

This dissertation describes development of some new catalytic systems involving gold and platinum salts. The use of these soft alkynophilic metals enables mild, chemoselective and efficient transformations of a variety of readily available acyclic substrates to a wide range of synthetically useful carbocyclic and heterocyclic products. For better understanding the thesis is divided into four chapters. The first chapter describes a novel AuCl3-catalyzed cyclization of 6-substituted cis-4,6-dien-1-yn-3-ols which proceeds via a 6-exo-dig pathway to give allyl cations, which subsequently undergoes a pinacol rearrangement to produce cyclopentenyl aldehyde core. This cycloisomerization of enynes via the intermediacy of allyl cation not only offered a chemoselective method for the preparation of cyclopentenyl aldehyde derivative but also opens up unprecedented reaction routes. Using chiral alcohol substrates, such cyclizations proceed with reasonable chirality transfer. The second chapter deals with a new one-pot Pt(II)-catalyzed synthesis of 9-oxabicyclo[3.3.1]nona-2,6-dienes from readily available 2-alkynyl-1-carbonylbenzenes and allylsilanes through tandem allylation/annulation of the oxo-alkyne functionalities with 2-substituted allylsilanes. This reaction sequence is proposed to proceed through three domino reactions including allylation of the carbonyl group, hydroalkoxylation of the alkyne, and a new ene-oxonium annulation. The third chapter describes the gold-catalyzed synthesis of 1,3-disubstituted aromatic rings through tandem allylation/enyne cyclization reaction. Treatment of alkynals with 2-substituted allylsilanes and PPh3AuCl/AgOTf (5/3 mol %) catalyst leads to the formation of 1,3-disubstituted benzenes efficiently. This reaction sequence comprises an initial allylation of aldehyde, followed by cycloisomerization of enynes; PPh3AuOTf is active in both steps. The last chapter discusses a stereoselective synthesis of bicyclo[3.2.1]oct-6-en-2-ones through Au(I)-catalyzed cycloisomerization of an allenene-acetal functionality. This cyclization is mechanistically significant because it involves an unprecedented 1,3-addition of a sp3-hybridized C–H bond to vinylcarbenoid moiety.