Valorisation of Renewable Building Blocks via Transition Metal Catalysis – Glycerol- and Amino Acid Derived Compounds in Hydrogen Borrowing and RuAAC Reactions
Doctoral thesis, 2017
To a large extent, organic building blocks are today obtained from petroleum-based products. From an environmental point of view, biomass-derived compounds are more sustainable alternatives to such oil-derived molecules. The 12 principles of green chemistry describe how chemical processes can be improved in terms of sustainability. With some of these principles as guidelines, this thesis considers the upgrading of renewable glycerol- and amino acid-derived compounds using two different atom economic catalytic reactions: the hydrogen borrowing reaction, and the ruthenium-catalysed azide-alkyne cycloaddition (RuAAC) reaction.
First, the glycerol derivatives solketal and 1,3-propanediol were investigated as starting materials in organic transformations using hydrogen borrowing methodology. Solketal was aminated with a set of secondary amines as well as sterically hindered primary amines, yielding the corresponding amino glycerol derivatives in good to excellent yields, using [Ru(p-cymene)Cl2]2 as the catalyst. Deprotection of the acetal gave the free amino diol, and this reaction sequence was used to synthesise the antitussive agent dropropizine in two steps from solketal. Furthermore, the iridium-catalysed α-alkylation of acetophenone with 1,3-propanediol was investigated. A mixture of products was obtained in moderate yields when using [Ir(cod)Cl]2 as the catalyst, while the selectivity could be improved by instead utilising an iridium-carbene complex as the catalyst. Hydrogen transfer methodology was also employed in the synthesis of chromanone scaffolds from 2’-hydroxyacetophenone and an alcohol. Brief mechanistic insight was gained considering the two reaction types via deuterium-labelling experiments and computational techniques, respectively.
In addition, chiral triazole δ-amino acids were constructed via a RuAAC reaction for the construction of foldamers. Eight chiral triazoles were synthesized in good yields. Computational conformational studies revealed that the synthesised monomers had several low energy conformations that could be part of a well-defined three-dimensional foldameric structure.
Finally, the RuAAC reaction was used in combination with a hydrogen borrowing cyclisation reaction for the construction of 1,5-fused triazole piperazines from a simple amino acid derived azide. A set of 14 different triazoles were synthesised in moderate to excellent yields, and 7 of these triazoles were successfully cyclised to give the desired 1,5-fused triazoles in two steps.
1 2 3-triazole
amino acid-derived azide