Industrially generated chiral waste materials are used as starting materials for the production of new potential active substances and reagents for enantioselective synthesis. The advantage of such an approach is that waste materials do not need to be incinerated or disposed of in any other way. The waste materials are available free of charge in sufficient quantities and the university's tight budget is not burdened by the purchase of these starting materials. A number of potentially useful substances are produced from the waste material. If the research is successful, the waste material suddenly becomes a sought-after resource.

Many sterically optically active substances are still most likely to be produced economically by separating enantiomers from the racemate. In this process, the unwanted enantiomer is produced in at least the same quantity as the homochiral optically active substance. In some cases, the unwanted enantiomer can be racemised and then recycled. However, this is often not possible. This is where we come in with our work and look for other possible uses for such waste. Specifically, for example, (1R,3R,5R)-2-azabicyclo[3.3.0]octane-3-carboxylic acid benzyl ester hydrochloride was provided free of charge by the German-French pharmaceutical company Sanofi-Aventis. In one step in the production of the active pharmaceutical ingredient ramipril, a racemate cleavage of (1RS,3RS,5RS)-2-azabicyclo[3.3.0]octane-3-carboxylic acid benzyl ester takes place. For the synthesis of the€E inhibitor ramipril, only the enantiomer (1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid benzyl ester hydrochloride is required; the same amount of waste material is inevitably produced and must be disposed of. The aim of the synthetic research is to find useful applications for the waste material, in particular to obtain new reagents and catalysts for enantioselective synthesis. The work is being continued. In the meantime, some further work on the utilisation of the waste substance (undesired enantiomer, not useful for ramipril synthesis) (1R,3R,5R)-2-azabicyclo[3.3.0]octane-3-carboxylic acid benzyl ester hydrochloride has become known from other universities and state research institutes.

The production and use of chitosan-based ion exchangers is also part of this field of work.

The work planned for the future should primarily lead to new reagents and catalysers for enantioselective synthesis. Furthermore, new chiral selectors for chromatographic racemate separation are to be developed.

Co-operation

Prof. Dr Francine Agbossou, Université de Lille / France

Prof. Dr Romero Brunet, Universidad Autonoma Madrid / Spain

Prof. Dr Byung Tae Cho, Hallym University / South Korea

Prof. Dr Silvian Jugé, Université Cergy Pontoise / France

Dr Arne Lützen / University of Oldenburg

Prof. Dr Santiago Luis, University Jaume I, Castellon / Spain

Prof. Dr Jaques Muzart, Université Reims / France

Prof. Dr Ingfried Stahl / University of Kassel

Selected publications 1999-2004

M. Kossenjans, M. Soebert, S. Wallbaum, K. Harms, J. Martens, H. G. Aurich: Synthesis of β-amino alcohols and thiols with 2-azabicyclo[3.3.0]octane backbone and their application in enantioselective catalysis, J. Chem. Soc. Perkin I 1999, 2353-2365. (DOI:10.1039/a902362c)

O. Juanes, J. C. Rodríguez-Ubis, E. Brunet M. Kossenjans, H. Pennemann, J. Martens: New chiral catalysts containing N,O-heterocycles derived from chiral amino alcohols, Eur. J. Org. Chem. 1999, 3323-3333. (DOI:10.1002/(SICI)1099-0690(199912)1999:12<3323::AID-EJOC3323>3.0.CO;2-W)

M. Kossenjans, J. Martens: Highly stereoselective synthesis of 1,3-amino alcohols via Mannich reaction, Tetrahedron: Asymmetry 1999, 10, 3409-3416. (DOI:10.1016/S0957-4166(99)00342-0)

S. Wassmann, J. Wilken, J. Martens: Synthesis and Application of C₂-symmetrical bis-β-amino alcohols based on the octahydro-cyclopenta[b]pyrrole system in the catalytic enantioselective addition of diethylzinc to benzaldehyde, Tetrahedron: Asymmetry 1999, 10, 4437-4445. (DOI:10.1016/S0957-4166(99)00475-9)

J. Wilken, M. Winter, I. Stahl, J. Martens: Enantioselective synthesis of 1-(1,3-dioxolan-2-yl)-3-pentanol from 3-(1,3-dioxolan-2-yl)-propanal by catalytic ethylation, Tetrahedron: Asymmetry 2000, 11, 1073-1075. (DOI:10.1016/S0957-4166(00)00030-6)

J. Wilken, M. Winter, I. Stahl, J. Martens: Catalytic enantioselective addition of diethylzinc to 1,3-dithian-2-yl substituted aliphatic aldehydes: a new approach to optically active 2-(hydroxyalkyl)-1,3-dithianes, Tetrahedron: Asymmetry 2000, 11, 1067-1071. (DOI:10.1016/S0957-4166(00)00029-X)

J. Wilken, S. Erny, S. Wassmann, J. Martens: New C₂-symmetric 2,4-bis(1-hydroxycyclopentyl)azetidines derived from(S)-1-phenylethylamine and their application in the enantioselective catalysis, Tetrahedron: Asymmetry 2000, 11, 2143-2148. (DOI:10.1016/S0957-4166(00)00155-5)

H. Pennemann, S. Wallbaum, J. Martens: Diastereoselective hydroboration of chiral enamines using an enantiomerically pure amine from an industrial waste material as the source of chirality, Tetrahedron : Asymmetry 2000, 11, 2133-2142. (DOI:10.1016/S0957-4166(00)00169-5)

H. Pennemann, S. Wassmann, J. Wilken, H. Gröger, S. Wallbaum, M. Kossenjans, D. Haase, W. Saak, S. Pohl, J. Martens: Utilisation of industrial waste materials. Part 19: Preparation of an enantiomerically pure helical nickel(II) complex using a new chiral tetradentate ligand derived from an unnatural amino acid, J. Chem. Soc. Dalton Trans. 2000, 2467-2470 (DOI:10.1039/b002130j)

C. Pasquier, S. Naili, A. Mortreux, F. Agbossou, L. Pélinski, J. Brocard, J. Eilers, I. Reiners, V. Peper, J. Martens: Free and Cr(CO)₃-Complexed Aminophosphine Phosphinite Ligands for Highly Enantioselective Hydrogenation of α-Functionalised Ketones, Organometallics 2000, 19, 5723-5732. (DOI:10.1021/om0006312)

N. Graf von Keyserlingk, J. Martens, D. Ostendorf, W. Saak, M. Weidenbruch: Utilisation of industrial waste materials. Part 20: Stereoselective cycloaddition of silylenes and disililene to an enantiomerically pure cyclic ketimine derived from an industrial waste material, J. Chem. Soc. Perkin I 2001, 706-710. (DOI:10.1039/b008708o)

N. Graf von Keyserlingk, J. Martens: Synthesis of optically active functionalised cyclic ketimines and their application in enantioselective catalysis, Tetrahedron: Asymmetry 2001, 12, 2213-2222. (DOI:10.1016/S0957-4166(01)00379-2)

N. Graf von Keyserlingk, J. Martens: Highly diastereoselective addition of N-Boc-pyrrolidin-2-yllithium to optically active ketimines: Synthesis of enantiomerically pure 1,3-imidazolidin-2-ones and diamines, Eur. J. Org. Chem. 2002, 301-308. (DOI:10.1002/1099-0690(20021)2002:2<301::AID-EJOC301>3.0.CO;2-Q)

M. I. Burguete, E. García-Verdugo, M. J. Vicent, S. V. Luis, H. Pennemann, N. Graf von Keyserlingk, J. Martens: New Supported β-Amino Alcohols as Efficient Catalysts for the Enantioselective Addition of Diethylzinc to Benzaldehyde under Flow Conditions, Org. Lett. 2002, 4, 3947-3950. (DOI:10.1021/ol026805o)

M. I. Burguete, M. Collado, E. García-Verdugo, M. J. Vicent, S. V. Luis, H. Pennemann, N. Graf von Keyserlingk, J. Martens: Development of small focused libraries of supported amino alcohols as an efficient strategy for the optimisation of enantioselective heterogeneous catalysts for the ZnEt₂ addition to benzaldehyde, Tetrahedron 2003, 59, 1797-1804. (DOI:10.1016/S0040-4020(03)00071-1)

S. V. Luis, B. Altava, M. I. Burguete, M. Collado, J. Escorihuela, E. Garcia-Verdugo, M. J. Vicent, J. Martens: Preparation and Optimisation of Polymer-Supported and Amino Alcohol Based Enantioselective Reagents and Catalysts, Ind. Eng. Chem. Res. 2003, 42, 5977-5982 (DOI:10.1021/ie030150t).