School of Chemistry - Theses
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ItemExtrusion-Insertion Reactions for Organic Synthesis: a Mechanism-Based Approach to Transition-Metal Assisted Synthesis of Amides and Alkenes( 2022)The imperative to achieve highly efficient and environmentally benign chemical synthesis stimulates the endless exploration of new reactions. The isoelectronic nature of heterocumulene species has been known for a long time. Extrusion and insertion reactions are well-known elementary reactions in organometallic chemistry. However, few cases have combined these concepts to invent new procedures for use in organic synthesis. This thesis describes a mechanism-based approach to establish a series of new classes of extrusion-insertion (ExIn) reactions for use in organic synthesis. Multistage mass spectrometry (MSn) experiments, solution-phase experiments in which either NMR or GC-MS are deployed to monitor formation of products, and density functional theory (DFT) are used to underpin the subsequent synthetic method development. In Chapters 3 and 4, the role of organometallic intermediates in the palladium mediated extrusion of carbon dioxide from carboxylic acids followed by insertion of isocyanates or allenes was investigated in the gas phase via mass spectrometry experiments and DFT calculations. Subsequent condensed phase studies led to the development of one pot methods for the synthesis of amides or alkenes with moderate to good yield under mild conditions. In the case of allene insertion, a crystalline sample of the organopalladium intermediate was isolated and its structure was determined via X-ray crystallography, thereby confirming the regioselectivity of the inserted product. To extend the scope of ExIn reactions, in Chapters 5 and 6, copper(I) and silver(I) salts were used in amide synthesis via CO2 extrusion from carboxylic acids and isocyanate insertion. The initial gas-phase experiments showed the formation of an organometallic species via decarboxylation of copper or silver carboxylate ions. Only the organoargentate ion reacted with phenyl isocyanate. The silver mediated reaction between carboxylic acids and isocyanates successfully yielded amides in the condensed phase. However, mechanistic studies based on 13C labelled experiments, gas-phase studies and DFT calculations uncovered a new base-catalysed condensation mechanism as an alternative pathway, whereby the acyl group is transferred from the carboxylate to the N atom of an isocyanate molecule. In Chapter 7, desulfination was explored as an alternative to decarboxylation for the formation of the crucial organometallic intermediate. Thus, a new type of ExIn reaction using sulfinate salts and phenyl isocyanate in the presence of palladium(II) salts was explored. The initial gas phase experiments and DFT calculations were carried out on phenanthroline ligated palladium cations and revealed that the sulfinate more readily undergoes extrusion due to its flexible coordination mode. The translation of this desulfination ExIn variant from the gas phase reactions into condensed phase was not successful. This is due to the fact that a biaryl homocoupling side reaction is preferred, as supported by DFT calculations, which revealed that the barriers for this side reaction are below that of the insertion reaction.