I. Steric effects in the synthesis of 2,3-dihydro-4-(1H)-quinolinones by the tandem Michael-SNAr reaction

Abstract

In the initial project, a one-pot tandem reaction sequence was developed for the preparation of 2,3-dihydro-4-(1H)-quinolinones by a Michael addition-SNAr reaction sequence. The steric environment of the Michael terminus plays a vital role in controlling the outcome of the reaction. Larger groups at this site reverse the Michael-SNAr reaction sequence and prevent the cyclization from occurring. Various amines were also examined to understand the steric control in this process. In the second project, we synthesized tetrahydrobenzo[b]azepine by tandem reduction Michael addition and reductive amination reaction. The third project focused on the development of a new synthetic route to prepare heteroarotinoids containing a nitrogen atom in the saturated heterocycle fused to the core aromatic ring. Heteroarotinoids exhibit significant anticancer activity with low toxicity toward normal cells. They regulate growth, differentiation, and apoptosis of cancer cells by interaction with nuclear proteins called retinoid receptors. By incorporating a nitrogen atom in the heteroarotinoid, the drug may exhibit increased activity, solubility and bioavailability. In Chapters IV and V, we aimed to synthesize supramolecular structures of porphyrins and phenyl acetylenes. Attempts were made to synthesize co-facial porphyrins and cyclized phenyl acetylenes that have central cavities capable of binding metals and small organic molecules. Neither of these studies was successful.