Exploring the reactivity of novel diazo-enones in the construction of heterocyclic compounds

Alavi, Sima (2023) Exploring the reactivity of novel diazo-enones in the construction of heterocyclic compounds. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

This thesis delves into the multifaceted world of diazo compounds, exploring their synthetic potential, mechanistic intricacies, and innovative applications. Chapter 1 of the thesis discusses the nucleophilic reactivity of the in situ generated malonic ester product from α-diazocarbonyls, followed by a tandem C−H functionalization/Coniaene cyclization of N-propargyl tethered indoles. This double functionalization of diazodicarbonyls generates a range of pyrrolo[1,2-a]-, pyrido[1,2-a]-, and azepino[1,2- a]indole products with good synthetic efficiency. Chapter 2 introduces the chemistry of α,β-unsaturated diazoketones or “diazo-enones. Diazo-enones are a structurally interesting class of α-diazocarbonyl compounds which have been steadily gaining interest from the synthetic community over the last decade. Characteristically, these multifunctional synthons possess three distinct reactive sites, a diazo-functional group, a ketone, and a C=C double bond. Chapter 3 describes a novel intramolecular rearranged cyclization by using a copper catalyst from indolyl α-diazocarbonyls starting from substituted indoles and diazo-enones. Activation of the diazo functional group under metal catalysis generates a spiro-cyclic indolenine-type intermediate, which rearranges to provide two distinct carbazoles upon oxidation. The study investigates the effects of the catalyst as well as the substituents on the migratory group involved in controlling the selectivity of the rearrangement. Chapter 4 develops a novel total synthesis of naphthofuranone containing natural products via a Hauser-Kraus annulation/O–H insertion process. By utilizing substituted phthalides via two tandem C–C bond formations in a one-pot process a class of fused furane ring systems have been formed. Several influential factors were identified in the formation of naphthofuranone derivatives; first, optimization studies showed the importance of the type of nucleophilic phthalide and secondly the choice of the base was revealed as the most effective factor alongside the work-up method. Chapter 5 provides a comprehensive overview of the research conducted in this thesis and outlines potential directions for future investigations.

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