Development of new catalysts for the vinylcyclopropane [5+2] cycloaddition and new approaches to cyclopentenone synthesis

Discovery of reactions that construct complex molecules in efficient ways is a central goal of chemical research. Our group designs and develops ways to effect cycloaddition reactions that are otherwise theoretically forbidden or difficult to achieve. Some examples include the vinylcyclopropane [5+2] and the dienyl-[2+2+1] reactions. These enable construction of seven- or five-membered ring compounds, ring sizes inaccessible through the Diels-Alder cycloaddition or Robinson annulation reactions.; Early examples of vinylcyclopropane [5+2] cycloadditions were intramolecular reactions between tethered vinylcyclopropanes and pi-systems. These reactions typically required refluxing substrates in toluene with modified Wilkinson's catalyst (Chapter 1). Since then work has been done to improve the efficiency, selectivity, and practicality of these reactions. Catalyst development studies include introduction of a water-soluble catalyst that effects both [5+2] and [4+2] reactions in water (Chapter 2). The catalyst can be extracted from the reaction mixture and re-used directly. Chirality of the cycloadducts of vinyl cyclopropane [5+2] reactions can be controlled using a chiral catalyst (Chapter 3). The first examples of enantiocontrolled [5+2] cycloaddition reactions and the absolute configuration of the products are reported. Rhodium-arene complexes have also been studied as catalysts for the [5+2] process (Chapter 4). In addition to providing the first X-ray structure of an eta6-naphthalene-rhodium complex (Chapter 5), pre-catalysts capable of executing high-yielding [5+2] reactions in minutes at room temperature are described.; Cyclopentenone synthesis had also been studied. This investigation began with the discovery that a diene provides a rate enhancement over other 2C "alkene" components---even norbornene---in the [2+2+1] reaction. Knowing this, an intermolecular "dienyl" Pauson-Khand reaction has been developed that enables direct preparation of functionalized vinylcyclopentenones from an alkyne, diene, and CO (Chapter 7). The efficiency this method puts it among most general solutions to the intermolecular Pauson-Khand problem. By contrast, an analogous [2+2+1] reaction among two alkynes and CO can produce a diversity of cyclopentadienones, benzoquinones, and alkyne oligomers. This problem is overcome by functionalizing one alkyne as the cyclopropenone, thus enabling a [3+2] approach to cyclopentadienones. This reaction directly accesses cyclopentadienones from a broad variety of aryl alkynes and enynes (Chapter 8).