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Browsing by Author "Rovis, Tomislav, 1968-, advisor"

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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.
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    The enantioseletive rhodium catalyzed [2+2+2] cycloaddition of alkenyl isocyanates with diaryl acetylenes and 1,2-disubstituted alkenyl isocyanates
    (Colorado State University. Libraries, 2010) Oinen, Mark Emil, author; Rovis, Tomislav, 1968-, advisor; Kipper, Matthew J., committee member; Williams, Robert Michael, committee member; Fisher, Ellen R., committee member
    Elaborating upon the recent discovery of a [2+2+2] rhodium-catalyzed cycloaddition of alkenyl isocyanates with various alkynes, the scope of this rhodiumcatalyzed cycloaddition with diaryl acetylenes was explored. The reaction with pentenyl isocyanate and diaryl acetylenes utilizing [Rh(C2H4)Cl]2 and 3,3'-substituted BINOL phosphoramidites as a catalyst predominantly affords vinylogous amide type products. Investigation into product selectivity reveals that both electronic and steric factors of the ligand have an influence on the product selectivity. Information gleaned from these studies allowed for a change in product selectivity for formation of lactam products with diaryl acetylenes. Selectivity for lactam product is at best 1:1.5 with BINOL phosphites. Vinylogous amide products are formed selectively (>20:1) in the cycloaddition using a variety of BINOL based phosphoramidites. Using 3,3' substituted BINOL based phosphoramidites promising enantioselectivies are obtained in the cycloaddition of diaryl acetylenes and pentenyl isocyanate. In the course of this investigation an interesting effect of substrate on the enantioselectivity was noticed. The ee of the reaction is highly dependent upon the nature of the diaryl acetylene. It was revealed that substrate affects the enantioselectivity by playing the role of spectator ligand in the reaction. Elucidation of the mechanism of the role of this spectator ligand was done by characterization of intermediates, kinetic analysis of the reaction rate and competition experiments between substrates. This effect of spectator ligands was exploited in a synthetically viable way to yield products with high and consistent enantioselectivities. By employing methyl nicotinate, a non-participating spectator ligand, as a stoichiometric additive synthetically useful enantioselectivities can be achieved. Finally, limitations existed within the scope of both alkynes and alkenyl isocyanates on the scope of the rhodium catalyzed [2+2+2] cycloaddition. Acetylene dicarboxylates, and 1,2-disubstituted alkenyl isocyanates were reaction partners that failed to provide cycloadducts under current reaction conditions. In both cases, the resultant cycloadduct would be interesting as they could provide additional synthetic handles for further manipulation of cycloadducts. Identification of undesired byproducts in these reactions allowed for the development of reaction conditions to reduce their formation of these by-products. The reduction in the formation of benzenoids formed from alkyne trimerization allowed for the production of mixtures of lactam and vinylogous amide products using acetylene dicarboxylates. With 1,2-disubstituted alkenyl isocyanates the implementation of reaction conditions which lead to the suppression of 2- pyridone lead to successful formation of the lactam products.