Intramolecular radical additions to pyridines, quinolines and isoquinolines

Abstract

This thesis is concerned with the development of intramolecular radical additions onto nitrogen containing heteroaromatics. Notably, 6-exolendo-tng radical cyclisations to C-2, C-3 and C-4 of pyridines and quinolines and C-3 and C-4 of isoquinolines have all been shown to be facile processes at neutral pi7. Cyclisations follow a chain pathway in which aromaticity in the heteroaromatic is re-established through loss of a hydrogen atom. S-exolendo Txig radical cyclisations to quinolines fail and appear to be more akin to 5-endo-tng processes than 5-exo-tng processes. Reactions that employ aryl iodides as radical precursors generally proceed more efficiently than related cyclisations employing aryl bromides.
It has been shown that the nature of the tether used to conjoin the radical precursor to the heteroaromatic can have a significant baring on the outcome of a reaction. When a fully saturated two carbon tether is used to conjoin an aryl radial to a pyridine an unprecedented rearrangement by zpi'o-radical cyclisation (5-exo-trig) - alkyl migration - aromatisation sequence competes with the 6-exo/endo-tvig cyclisation pathway. When an E alkene is used to tether the radical precursor to a pyridine, or if the heteroaromatic is a quinoline or isoquinoline, only the 6-exolendo-tng pathway is followed. Using the methodology developed, approaches to the alkaloid avicine are discussed. A comparison of various techniques commonly employed to generate aryl radicals from aryl iodides is also reported. A literature review concerning radical additions to nitrogen containing heteroaromatics is presented.

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ORCID for David C. Harrowven: orcid.org/0000-0001-6730-3573

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