Carbohydrates as Synthetic Tools in Organic Chemistry - Stereoselective Cosntstruction Quaternary Stereocentres

• Applicant: Professor Dr. Holger Butenschön, since 8/2015
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2007 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 38641771

Asymmetric catalysis using metal complexes of chiral ligands is a powerful tool for stereoselective synthesis of chiral compounds. Bis(oxazolines) are one important type of chiral complex ligands, offering high levels of enantioselectivity in many reactions, e.g. copper-catalysed asymmetric cyclopropanation.In the course of our work we have introduced new bis(oxazolines) based on D-glucosamine. Subsequently the ligand scaffold was systematically modified and the impact of these modifications on the asymmetric induction of cyclopropanation reactions was examined. As a result of these studies an improved ligand was obtained, which offered excellent results even with challenging substrates and was successfully employed in the asymmetric synthesis of a natural product.Cyclopropanation reactions on indoles have only rarely been reported in the literature and an enantioselective version of this transformation has not been described yet. Using our new bis(oxazoline) ligands, we have performed the first enantioselective cyclopropanations on indoles, which yielded the products in high enantiomeric excess.This project aims to establish enantioselective cyclopropanation of indoles as a key step for the preparation of complex structures containing all-carbon quaternary stereocentres, which still is a great challenge in organic synthesis. The reaction of different indole derivatives yields cyclopropanes, which can easily be converted into the scaffolds of various biologically active natural products and drug candidates: 3-alkylated indoles will furnish pyrroloindolines and 3,3'-spiroindoline derivatives, while reactions on 2,3-anellated indoles will lead to the echiboline scaffold (a tetrahydro[imineethano]carbazole derivative). To demonstrate the high synthetic value of this approach, the alkaloide natural products physositigmine and esermethole (pyrroloindoline type), horsfiline and coerulescine (3,3'-spiroindoline type) and minfiensine (echiboline type) will be prepared.All cyclopropanations of indole substrates will be performed using our carbohydrate-derived bis(oxazoline) ligands. As the enantiomers of these ligands are not easily available, studies towards the optimisation of pseudo-enantiomeric carbohydrate-ligands are planned. The pseudo-enantiomeric ligands we prepared so far do indeed reverse the direction of the asymmetric induction but offer as yet only moderate levels of enantioselectivity. As an alternative, a commercially available, conventional bis(oxazoline), also reversing the asymmetric induction, may be employed.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Mike M. K. Boysen, until 7/2015