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Research

Iodine in Oxidative Coupling Reactions

The direct oxidative coupling of a C-H and a X-H bond (X=C, N, O, S) to form a new C-X connection is an efficient synthetic approach since further derivatization of the reaction partners is not unnecessary. Typically expensive and toxic transition metals must be used as catalysts or oxidation mediators for such valuable transformations. We intensely investigate iodine and iodide-salts as metal-free alternatives in oxidative C-X bond formations. The combination of catalytic amounts of a iodine source and an external oxidant leads to in situ formed electrophilic iodine species which can be used for a variety of oxidative coupling reactions through an in situ iodination mechanism. As an example, we could develop the first metal-free 2-amination protocol for benzo[d]oxazoles. link

© Nachtsheim

Iodine in Oxidative Coupling Reactions

The direct oxidative coupling of a C-H and a X-H bond (X=C, N, O, S) to form a new C-X connection is an efficient synthetic approach since further derivatization of the reaction partners is not unnecessary. Typically expensive and toxic transition metals must be used as catalysts or oxidation mediators for such valuable transformations. We intensely investigate iodine and iodide-salts as metal-free alternatives in oxidative C-X bond formations. The combination of catalytic amounts of a iodine source and an external oxidant leads to in situ formed electrophilic iodine species which can be used for a variety of oxidative coupling reactions through an in situ iodination mechanism. As an example, we could develop the first metal-free 2-amination protocol for benzo[d]oxazoles. link

Iodine in Oxidative Domino Reaction

In addition to fundamental oxidative C-X bond forming reactions, we are highly interested in iodine-mediated oxidative domino reaction to construct carbo- and heterocyclic core structures from readily available starting materials. As an example, we recently developed an efficient halocyclization/cycloaddition/ elimination cascade reaction that is truly catalytic in iodine. link

 

Furthermore, we are interested in iodide-catalyzed oxidative domino reaction for the de novo synthesis of interesting heterocyclic core structures. In this regard, we could recently develop a novel iodide-catalyzed decarboxylative iodination/oxidation/condensation cascade to construct highly substituted oxazoles from aryl ketones and amino acids. link

Hypervalent Iodanes in Metal-free C-C and C-X Bond Forming Reactions

Hypervalent iodine compounds (iodanes) have found widespread applications as mild oxidants and mediators in oxidative coupling reactions. We utilize known hypervalent iodanes in so far unknown coupling reactions and in addition we are searching for novel hypervalent iodine compounds as versatile chemical tools in organic synthesis. In the course of a novel synthetic route to arogenate, a biosynthetic precursor of the aromatic amino acids tyrosine and phenylalanine, we could develop a hypervalent iodine-mediated spirocyclization of 2-(4-hydroxybenzamido)acrylates. Here, the first direct iodane-mediated 6-ring spirolactonization reaction is observed. link

We are also interested in the iodane-mediated de novo synthesis of heterocycles via oxidative C-N- and/or C-O-bond forming steps. As an example we could recently develop a novel synthetic route to 2,5-disubstituted oxazoles through an intramolecular cyclization of highly substituted enamides. link

© Nachtsheim

Chemical Evolution - Self-Assembly and Catalysis

The molecular mechanisms for the transition of primordial organic molecules such as amino acids, sugars and fatty acids to primitive self-replicating cell-like vesicles with an independent genotype, phenotype and metabolism are unknown. In this regard we investigate the self-assembly process of simple amino acid and nucleotide-based small organic molecules into higher ordered structures. Here we are interested in the molecular mechanism of self-assembly itself, the catalytic activity of the assemblate in reactions relevant for abiogenesis.

© Nachtsheim

Novel Soft Materials

The self-assembly of small peptides is aqueos solutions is a difficult task since hydrogen bonding interactions are heavily disturbed by competing solvent interactions. In general small peptides which are designed to self-assemble in water, for example to generate hydrogels, need to be unnaturally modified either at their N- or C-terminus with highly lipophilic groups to induce strong Van-der-Waals interactions. As an alternative, aromatic residues such as Fmoc-protecting groups, are installed to cause pi-stacking interactions. We could recently find the lowest molecular weight peptide-based hydrogelators based on unmodified proteinogenic amino acids. These cyclic dipeptides (diketopiperazines) can be easily synthesized, are biodegradable and can be combined to form novel hydrogels with easy tunable morphological and mechanical properties. link