Metal-based asymmetric catalysis with N-heterocyclic carbene ligands, and, Lessons in asymmetric catalysis from a total synthesis of baconipyrone C

Chapter 1. Design, synthesis, and reactivity of enantiomerically pure Ru catalysts that incorporate steric and electronic modifications of the first generation chiral catalyst are disclosed. These studies provide insight into differences in activity, the mechanism of olefin metathesis, and selectivity in stereogenesis. Modifications of the chiral Ru catalyst lead to an increase in reactivity by over two orders of magnitude relative to the previous chiral Ru catalyst. Some of the newly developed chiral Ru catalysts expand the scope of asymmetric olefin metathesis by promoting asymmetric ring-opening cross metathesis and asymmetric ring-closing metathesis reactions that cannot be effected by the first generation chiral Ru catalyst.; Chapter 2. The scope of Ru-based asymmetric olefin metathesis is expanded with the introduction of oxabicyclic cycloheptenes as substrates in the asymmetric ring-opening cross metathesis reaction. A new Ru-iodide complex is introduced which delivers superior enantioselectivity in asymmetric metathesis reactions. The collective body of Ru-based asymmetric metathesis data is used to formulate a mechanistic hypothesis and a model for the mode of enantioselectivity.; Chapter 3. An enantioselective total synthesis of baconipyrone C is described. The total synthesis highlights recent advances in asymmetric catalysis with N-heterocyclic carbenes: Ru-catalyzed asymmetric olefin metathesis and Cu-catalyzed asymmetric allylic alkylation. Other highlights of the total synthesis include a new strategy for the construction of gamma-pyrone rings and the use of allylsilane tether ring-closing metathesis/oxidation sequence as an alternative to olefin cross metathesis.; Chapter 4. The synthesis of baconipyrone C required the development of beta-trisubstituted olefin electrophiles for asymmetric allylic alkylation. The development of these electrophiles in asymmetric alkylation continues with the expansion of the method to include substrates with a variety of functional groups and substitution patterns. The introduction of alkylaluminum nucleophiles for asymmetric alkylation broadens the scope of alkyl groups that can be used in the reaction.