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Browsing by Author "Friedman, Rebecca Ann Keller, author"

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    Rhodium-catalyzed cycloadditions between alkenyl isocyanates and alkynes: study of scope, mechanism and applications toward total synthesis
    (Colorado State University. Libraries, 2010) Friedman, Rebecca Ann Keller, author; Rovis, Tomislav, 1968-, advisor; Kennan, Alan J., committee member; Prieto, Amy L. (Amy Lucia), committee member; Shi, Yian, committee member; McNeil, Michael R., committee member
    Rhodium-catalyzed cycloadditions between alkenyl isocyanates and unsymmetrical, internal alkynes has been studied. A wide variety of alkynes have proven successful components in the [2+2+2] cycloaddition. Excellent yields and enantioselectivities have been achieved in the resulting indolizidinone products. Furthermore, a single regioisomer is obtained for the vast majority of alkynes subjected to reaction conditions. A logical explanation for the highly regioselective insertion for internal, unsymmetrical alkynes was provided. Small variations in the electronics and/or steric bulk of the alkyne substitution were sufficient to predictably control the insertion of the alkyne into the initial rhodacycle. Mechanistic insight into the rhodium-catalyzed [4+2+2] cycloaddition between dienyl isocyanates and alkynes has been achieved. A series of competition and slow addition experiments, alongside analysis of enantioselectivity and product formation, provided evidence for a proposed mechanism of the [4+2+2] cycloaddition. It was determined that the diene preferentially coordinates to the rhodium, in the presence of a terminal alkyne, to provide eight-membered bicyclic azocene products. Steps towards the total synthesis of natural product Secu'amamine A have been made. The bicyclic core of the molecule has been successfully synthesized utilizing rhodium-catalyzed [2+2+2] methodology developed within the Rovis group. Additionally, a successful, diastereoselective 1,4-reduction of the resulting vinylogous amide product and subsequent deprotection of an enyne side-chain provided an intermediate that is hypothetically two steps (an alpha-oxidation and 2+2+1 cycloaddition) away from Secu'amamine A.