Iridium Catalyzed Carbon- Heteroatom Bond Forming Reactions via Hydrogen Transfer : Method Development and Mechanistic Elucidations

Sammanfattning: The present thesis describes the applicability of two different iridium(III) complexes for C-O and C-N bond forming reactions. The different projects described in this work are united by the use of an iridium catalyst bearing a functionalized N-heterocyclic carbene ligand. These catalysts operate through a hydrogen transfer mechanism to afford the desired products. This approach gives access to a variety of valuable products in a sustainable and atomeconomical manner, generating water as the only byproduct.In Chapter 1, a general introduction to catalysis, followed by a more detailed description of organometallic complexes and their use in hydrogen transfer reactions is described. An overview of different mechanistic studies that have been employed within this thesis is also provided.Chapter 2 describes the use of an alkoxy-functionalized iridium-NHC complex, previously reported by our group, on cyclodehydration reactions (Paper I). A range of cyclic ethers are obtained from the corresponding diol compounds. Mechanistic studies confirmed an unexplored hydrogen transfer pathway to be operating for the majority of the substrates.In Chapter 3, a new amino-functionalized iridium-NHC catalyst is designed and synthesized, aiming at improving the reactivity compared to previous reports. Then, its outstanding efficiency on carbon-nitrogen bond forming reactions is depicted in different protocols (Papers II, III and IV).Paper II achieves the base-free and selective mono-N-alkylation of amines with alcohols mostly at room temperature. Mechanistic studies are performed to gain a better understanding of the catalytic cycle by combining experimental and in silico studies.In Paper III, the use of this catalyst to access N-modified amino acids is described. Excellent group tolerance allowed for the synthesis of more than 100 compounds. Moreover, quantitative yields are obtained in all cases without the need of tedious derivatization/purification steps. In addition, convenient scalability, recyclability and deuterium labelling studies are also presented. Further applicability of these compounds as high-value building blocks for the synthesis of N-modified peptides is demonstrated.In Paper IV, the catalyst is used for the direct mono-N-alkylation of a range of aminosugars with alcohols. The method is developed to be applied on unprotected carbohydrates, that enables to access these important organic molecules in a direct, and thus sustainable, manner, avoiding unnecessary protection and deprotection steps.