| Six-membered cyclic enaminones (2,3-dihydropyridin-4(1H)-ones) are versatile synthetic intermediates for the preparation of piperidine-containing biologically active compounds such as indolizidines and quinolizidines alkaloids. In this thesis, the functionalizations of cyclic enaminones have been described. In addition, novel IKKbeta inhibitors have been discovered from the cyclic enaminone derivatives.;A palladium-catalyzed C5 arylation of cyclic enaminones using arylboronic acids has been developed. A unique mixture of Cu(OAc)2 and CuCl 2 oxidants is essential for efficient cross-coupling of electronically diverse boronic acids. In addition to serving as palladium reoxidants, these reagents are believed to assist aryl delivery through a putative arylcopper intermediate.;Another direct C5 arylation reaction has been developed using diaryliodonium tosylates under metal-free and copper-catalyzed reactions. Metal-free conditions offer a green alternative, where the use of heavy transition metals has been excluded. On the other hand, copper-catalyzed conditions provide highly efficient C5 arylation method under mild conditions within a short period of time.;We have developed direct C6 arylation using the oxidative boron-Heck reaction that proceeds with excellent selectivity over C5 arylation and conjugate addition reactions. C6 arylated cyclic enaminone can serve as an intermediate in total synthesis of lasubine II. Furthermore, an acid-controlled reactivity switch to a conjugate addition reaction is viable when the reaction is carried out with N-carbamylated substrates.;Novel scaffolds that incorporate cyclic enaminone motifs were designed and synthesized using copper-catalyzed amidation and reductive amination. Biological assays showed that some analogues possess IKKbeta inhibitory activity. |
