Enantioselective dearomatisation by HB catalysis

The development of novel medications and drugs for illnesses is an important purpose and service of the pharmaceutical industry. The methods for the preparation of a large portion of drugs arise from the application of synthetic organic chemistry. In recent decades green aspects of research like sustainability, efficiency and safety have took on a greater significance in this field. This encompasses the development of mild, non-toxic reagents to improve the safety profile of the waste, and multi-step reactions (dominoandem) to reducing waste in general by gaining efficiency. In this project a reaction that is typically performed under high pressure of molecular hydrogen (dearomatisation of nitrogen-containing cyclic molecules) shall be carried out using an iridium catalyst and the cheap, abundant feedstocks methanol and formaldehyde. This constitutes a multi-step reaction and should open access to a wide variety of products. During the second step of the reaction an additional alkylation step with formaldehyde takes place, a feature which further increases product complexity and is not available for classical dearomatisation approaches. The method developed by Prof. Donohoe in Oxford shall be expanded in the course of this project to control the absol ute stereochemistry (3-dimensional positioning of atoms in the molecule, mirror image). To achieve this ambitious goal 3-dimensionally defined iridium catalysts will be tested for their reactivity in this application. Target of the dearomatisation reaction are heterocyclic aromatic compounds like iso(quinolines) and pyridines which are of great importance in pharmaceutical chemistry. A general method to transform the flat heterocycles into 3-dimensionally defined, highly complex products bears enormous potential for drug discovery and medicinal chemistry because new chemical space is hereby accessed.

The development of novel medications and drugs for illnesses is an important purpose and service of the pharmaceutical industry. The methods for the preparation of a large portion of drugs arise from the application of synthetic organic chemistry. In recent decades "green" aspects of research like sustainability, efficiency and safety have took on a greater significance in this field. This encompasses the development of mild, non-toxic reagents to improve the safety profile of the waste, and multi-step reactions (domino/tandem) to reducing waste in general by gaining efficiency. In this project a reaction that is typically performed under high pressure of molecular hydrogen (dearomatisation of nitrogen-containing cyclic molecules) shall be carried out using an iridium catalyst and the cheap, abundant feedstocks methanol and formaldehyde. This constitutes a multi-step reaction and should open access to a wide variety of products. During the second step of the reaction an additional alkylation step with formaldehyde takes place, a feature which further increases product complexity and is not available for classical dearomatisation approaches. The method developed by Prof. Donohoe in Oxford shall be expanded in the course of this project to control the absolute stereochemistry (3-dimensional positioning of atoms in the molecule, mirror image). To achieve this ambitious goal 3-dimensionally defined iridium catalysts will be tested for their reactivity in this application. Target of the dearomatisation reaction are heterocyclic aromatic compounds like iso(quinolines) and pyridines which are of great importance in pharmaceutical chemistry. A general method to transform the flat heterocycles into 3-dimensionally defined, highly complex products bears enormous potential for drug discovery and medicinal chemistry because new "chemical space" is hereby accessed.