Implementing amino acids in manganese-catalyzed biologically inspired oxidations: g-lactonization and ligand design

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Most of the organic molecules used in chemical industry (and their synthetic precursors) contain oxygen atoms in their structure. One of the most convenient methods for the preparation of oxygenated compounds is the direct oxidation of hydrocarbon C-H or C=C bonds. Currently, the methodologies that are often used to carry out these transformations rely on the use of stoichiometric oxidants with poor atom economy and second or third row transition metals. A different scenario is found in metalloenzymes, in which oxidations occur with high levels of efficiency and selectivity under very mild experimental conditions. Key to the high efficiency of oxygenases is the well-defined first coordination sphere around the metal, being the ligands that are directly bound to the metal the ones that have more impact in its reactivity. Because of that, enzymatic active sites have been taken as source of inspiration for the development of new oxidation catalysts based on iron and manganese coordination compounds with N-based tetradentate ligands. In the first part of this thesis, the main characteristics of these complexes are discussed, exploring the rationale behind the evolution of their structure (Chapter III). These complexes are then applied in the C-H functionalization of a-amino acids, in which a general methodology for the preparation of non-natural analogues based on the g-lactonization of amino acids is presented (Chapter IV). Site-selective oxidation of 1º, 2º and 3º C-H bonds is obtained in high yields and good to excellent diastereo- and (where applicable) enantioselectivities. Another important feature in the structure of oxygenases is the second coordination sphere around the metal. The large network of amino acid and peptide chains that surround the enzymatic active site is key to obtain high selectivities, as it can be engaged in non-covalent interactions between them and with the substrate promoting specific selectivities. In the second part of this thesis, a step further in the design of artificial catalysts is done, and 2nd coordination sphere is considered. First, a literature review on oxidation catalysts that use amino acids in combination with metal complexes is performed (Chapter V), evidencing the small number of examples reported up to now. With all these precedents, the last chapter of this thesis describes a catalytic system in which the second coordination sphere is modified using supramolecular chemistry (Chapter VI). A manganese complex is decorated with an 18-benzocrown-6 ether that interacts with protonated amino acids in the remote position. Supramolecular recognition allows the proper location of the carboxylic acid moiety to access the first coordination sphere and get involved in the catalytic cycle. This system permits an enzyme-like activation of H2O2 using a single acidic residue and the tuning of the enantioselectivity in asymmetric epoxidations by the modification of the 2nd coordination sphere ​
​L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc/4.0/

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