Development of Carbonyl Functionalization Methods Towards Sustainable Synthetic Strategies

Abstract

Carbonyl compounds represent a fundamental and versatile class of organic mole-cules that play a central role in both synthesis and biology. In synthetic chemistry, traditional methods for carbonyl functionalization generally involve the use of haz-ardous reagents or the production of large amounts of waste all of which contribute to environmental problems. Consequently, the development of sustainable strate-gies for carbonyl functionalization is of utmost importance. This thesis explores two strategies for carbonyl functionalization: aerobic oxidative N-heterocyclic carbene (NHC) catalysis and the visible-light induced Zimmerman-O’Connell-Griffin (ZOG) rearrangement. The objective is to develop efficient carbon-yl functionalization methods that contribute to the advancement of sustainable chemistry through the investigation of these strategies. Aerobic oxidative NHC catalysis is a synthetic strategy for the direct conversion of aldehydes to activated carbonyl species known as acyl azolium intermediates. These intermediates are pivotal for the synthesis of various substances, including highly substituted benzene derivatives. Within this approach, aerial oxygen is the terminal oxidant, a desirable choice due to its cost-effectiveness and the production of water as the sole byproduct. However, the low reactivity of oxygen necessitates the development of a specialized catalytic system. By incorporating electron transfer mediators to the reactions (ETMs), mild aerobic oxidation conditions can be achieved. These ETM-assisted, aerobic NHC-catalyzed transformations demonstrate high selectivity and reduced waste generation. The ZOG rearrangement represents a strategy for the generation ketenes another form of an activated carbonyl species. In this reaction we use visible light to trigger a rearrangement of a photosensitive substrate leading to in situ formation of the ketene. Ketenes are highly reactive intermediates capable of engaging with a diverse array of substrates, thereby enabling broad synthetic utility. Remarkably, no addi-tional reagents or catalysts are needed to trigger this photochemical reaction. With only the reactants and visible light, a broad range of products can be obtained under mild conditions and generating a minimal amount of waste.