Friedman, Rebecca Ann Keller, authorRovis, Tomislav, 1968-, advisorKennan, Alan J., committee memberPrieto, Amy L. (Amy Lucia), committee memberShi, Yian, committee memberMcNeil, Michael R., committee member2007-01-032007-01-032010http://hdl.handle.net/10217/44960Rhodium-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.born digitaldoctoral dissertationsengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.organometallicmethodologycycloadditionAlkynesRhodium catalystsRing formation (Chemistry)Combinatorial chemistryText