Synthesis and utilization of novel diazo-enones; total synthesis of furan-based target molecules

Abstract

This thesis focuses mainly on the synthesis and application of diazo compounds. More specifically, a unique subclass of α-diazocarbonyl compounds, known as diazo-enones. This category features both an α,β-unsaturated carbonyl moiety and a diazo group. These multifunctional compounds can be utilized as Michael acceptors, dienophiles, or carbene precursors, enabling the construction of complex organic compounds. This work focuses on developing a new method for synthesizing acceptor-type diazo-enone and its β-substituted derivatives without using diazomethane. Additionally, exploring their application in the construction of polycyclic heteroaromatic compounds through a novel Hauser-Kraus type annulation. Traditionally, the Hauser-Kraus reaction involves a [4 + 2] cycloaddition between phthalides and α,β-unsaturated carbonyl compounds to build naphthalene derivatives. Here, diazo-enones serve as surrogates for the classical α,β-unsaturated compounds, leading to the efficient synthesis of naphthofuran scaffold via construction of two C–C and one C–O bonds in one step. This structural motif is found in many natural products such as furomollugin. This thesis also covers the total synthesis of the antimicrobial natural product isomicrocionine-3. This synthetic route features a novel 3-substituted furan construction via a monowave-mediated [4 + 2]/retro-[4 + 2] reaction, furnishing the natural product in a 7 step convergent synthesis.