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Browsing by Author "McNeil, Michael R., committee member"

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    Application of metallacycles for the synthesis of small molecules
    (Colorado State University. Libraries, 2011) Williams, Catherine Marie, author; Rovis, Tomislav, advisor; Wood, John L., committee member; Finke, Richard G., committee member; Shores, Matthew P., committee member; McNeil, Michael R., committee member
    A method for the nickel-catalyzed hydrocarboxylation of styrene derivatives has been developed that affords exclusively the branched carboxylic acids in moderate to excellent yields. The reaction scope is tolerant of a variety of electron-deficient ortho-, meta-, and para-styrene analogues containing ester, ketone, nitrile, and halide functionalities. The reaction is remarkably efficient, proceeding well with as little as 1 mol% Ni(acac)2 and 2 mol% Cs2CO3. A system for carbon dioxide sequestration and release in organic polymers has been investigated. Although evidence supporting successful carbon dioxide fixation has been found, the envisioned system is not a practical means of sequestration and release. A rapid approach for the synthesis of Abyssomicin C has been developed utilizing the desymmetrization of meso-dimethylglutaric anhydride. Closely modeled after Sorensen's synthesis, our route bypasses the more inefficient beginning steps to intercept the completed synthesis at the Diels-Alder precursor.
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    Progress towards the total synthesis of the welwitindolinone alkaloids and the discovery of a novel tandem O-H insertion Conia-ene cyclization
    (Colorado State University. Libraries, 2011) Freeman, David Blandy, author; Wood, John L., advisor; Kennan, Alan J., committee member; Ferreira, Eric M., committee member; Shores, Matthew P., committee member; McNeil, Michael R., committee member
    The broth of blue-green algae Hapalosiphon wewitschii and Westiella intricate was shown to possess interesting biological activity, including insecticidal and P-glycoprotein inhibiting capabilities. Upon further investigation, the welwitindolinone alkaloids were isolated from the lipophilic extracts and shown to be responsible for the observed biological activity. Herein are described efforts towards the total synthesis of the welwitindolinone alkaloids and novel chemistry developed in the process. In efforts towards N-methylwelwitindolinone C isothiocyanate, we employed a sequential O-H insertion Claisen rearrangement to provide compounds capable of undergoing a [3+2] dipolar cycloaddition to access the bicyclo[4.3.1] core. Attempts to install the requisite quaternary center of N-methylwelwitindolinone C isothiocyanate during the [3+2] dipolar cycloaddition event were unsuccessful. Ultimately, a chloronium-ion semi-Pinacol rearrangement was utilized to install the key quaternary center. Due to complications encountered during the synthesis of N-methylwelwitindolinone C isothiocyanate we shifted our focus to N-methylwelwitindolinone D isonitrile. Investigation into the construction of the bridged ether embedded within N-methylwelwitindolinone D isonitrile led to the discovery of a novel tandem O-H insertion Conia-ene cyclization.
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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.