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A general catalytic β-C–H carbonylation of aliphatic amines to β-lactams 10.17863/CAM.21894 Chappell, Benjamin Graham Neil 0000000184347818 Gaunt, Matthew Carbonyl compounds are of central importance to organic chemistry and their reactions have been described as the ‘backbone of organic synthesis’. Over recent decades, palladium-catalysed C–H carbonylation reactions have emerged as a powerful means of introducing carbonyl motifs to organic molecules. This thesis describes the development of a general C–H carbonylation reaction of secondary aliphatic amines, which provides facile access to synthetically useful β-lactam products. The first part of the thesis explores the scope and limitations of this reaction. Whilst previous C(sp3)–H carbonylation methodologies were restricted to ‘Type F’ secondary aliphatic amines, the reaction described in this thesis was found to be broadly applicable all structural sub-classes of secondary aliphatic amine. Furthermore, the reaction was found to be remarkably tolerant of functional groups, even those that commonly cause issues in palladium-catalysed C–H activation reactions such as heteroaromatics and thioethers. The second part of this thesis investigates the mechanism of this C–H carbonylation reaction. Interestingly, the reaction was found not to proceed via a traditional C–H carbonylation mechanism comprising of C–H activation, 1,1-migratory carbon monoxide insertion and reductive elimination. Instead, a new mechanistic paradigm for palladium-catalysed C–H carbonylation is proposed, which invokes a putative ‘palladium anhydride’ intermediate. A series of DFT calculations and experiments were conducted in order to support this mechanistic proposal. The work described within this PhD thesis was published in Science. University of Cambridge 2018-06-02 Thesis Doctoral Doctor of Philosophy (PhD) en Herchel Smith Scholarship Trinity College External Research Scholarship https://www.repository.cam.ac.uk/handle/1810/274756 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/939b0fb7-0bbf-41e7-b52d-fc3105e14ef5/download 46c273314ea446ffa5261776ddd6ef7b https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/9a7a5f48-a216-4a4b-9a49-c6a1604e8f04/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Palladium C–H activation Carbonylation Catalysis Organic Chemistry Beta lactams Aliphatic amines