Exploration of ruthenium (II) catalyzed processes: From [2+2] cycloadditions to the discovery of new rections

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Villeneuve, Karine

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University of Guelph


Transition metal-catalyzed [2+2] cycloadditions are useful tools for the synthesis of cyclobutane and cyclobutene rings. This thesis discloses the investigation of two aspects of the ruthenium-catalyzed [2+2] cycloaddition between an alkyne and a bicyclic alkene, as well as new ruthenium-induced reactions of oxabicyclic alkenes. First, haloacetylenes were found to be compatible with the ruthenium-catalyzed [2+2] cycloaddition reaction, and good yields were usually obtained (up to 90%). In general, the presence of the halide moiety enhanced the reactivity of these alkynes towards the reaction, and a trend following CI>Br>I was observed. Their use displays a synthetic importance, as they allow further functionalization of the main molecule core in a variety of ways.* The second component explored was the development an asymmetric version of the ruthenium-catalyzed [2+2] cycloaddition. Three classes of chiral alkynes were examined: acetylenic acyl sultams and oxazolidinones, ynamides and propargylic alcohol derivatives. Chiral acetylenic acyl sultams were found to be very efficient chiral auxiliaries for the [2+2] cycloaddition, furnishing high diastereoselectivities (up to dr= 99:1) and yields (up to 95%). On the other hand, chiral ynamides were shown to be less reactive towards the [2+2] cycloaddition reaction, and modest diastereoselectivities were obtained (up to dr= 75:25). Also utilized to induce asymmetry in ruthenium-catalyzed [2+2] cycloaddition were chiral propargylic alcohol derivatives. The low to moderate diastereoselectivity (up to dr=84:16) was highly dependent on the nature of both unsaturated partners. During the course of studying the scope of the reaction with chiral propargylic alcohols, several unprecedented reactivity pathways of bicyclic alkenes were discovered. The nature of the major product was selected by altering the reaction components (alkene, alkynol) and conditions (additive, solvent, ruthenium catalyst): CpRu(COD)I in THF furnished the [2+2] cycloadduct, CpRu(COD)CI in CH3CN or THF mainly provided the cyclopropane product, whereas Cp*Ru(COD)CI in McOH produced the isochromene. These three products originated from common reaction intermediates. In contrast, treating solely an oxabenzonorbornene with the ruthenium catalyst resulted in the isomerization to the corresponding 1,2-naphthalene oxide. This reaction occurred readily and generally with highl regioselectivity.



ruthenium-catalyzed [2+2] cycloaddition, alkyne, bicyclic alkene, ruthenium-induced reactions, oxabicyclic alkenes