Explorations in Cobalt Promoted Cyclocarbonylation, Intramolecular Cyclization of Vinyl Ethers, and Formation of Metal-Carbene Complexes with mRNA 5’-Cap Analogs

Chapter one describes a [2+2+1+1] reaction for the synthesis of quinones from alkynes. Cobalt octacarbonyl, in a mechanism reminiscent of the Pauson-Khand reaction, combines two equivalents of an alkyne with two equivalents of carbon monoxide via a series of insertions and reductive eliminations, to form a quinone. In theory, this reaction provides rapid access to complicated quinone structures. Unfortunately, a competing [2+2+2] reaction which is catalyzed by cobalt to give benzene derivatives out competes the desired reaction, and high yields were never achieved. Chapter two details the investigation of three different intramolecular cyclization reactions which endeavor to take advantage of the unique reactivity of vinyl ethers. Using complex vinyl ether substrates synthesized by methods previously described by our group, these reactions should provide easy access to relatively complex fused ring systems. The chapter primarily focuses on the [2+2] cycloaddition of vinyl ethers with both ketenes and ketene iminium ions, which yield cyclobutanone products. Also described is the investigation into the nucleophilic attack of epoxides by vinyl ethers. Although perfectly sound from a mechanistic perspective, as born out by intermolecular examples, the challenge of performing these intramolecular reactions remains the incompatibility of vinyl ethers with certain necessary reaction conditions. Chapter three describes the synthesis of a metal carbene complex using gold and an analog of the 5’-cap of mRNA; the first such example to be synthesized via in situ generation of a carbene at the C8 position of guanosine. The only previous example was generated via an oxidative addition with platinum under extreme conditions. In our example we use extremely mild conditions which suggest the possibility of forming such a complex with mRNA oligonucleotides, and perhaps even in vivo. Such reactivity of mRNA is unprecedented and could lead to interesting pharmaceutical possibilities