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Combinatorial Libraries Reloaded[1]


Reetz,  Manfred T.
Research Department Reetz, Max-Planck-Institut für Kohlenforschung, Max Planck Society;
Department of Chemistry, Philipps-University;

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Reetz, M. T. (2018). Combinatorial Libraries Reloaded[1]. Israel Journal of Chemistry, 58(1-2), 52-60. doi:10.1002/ijch.201700091.

This essay constitutes a personal assessment of two quite different projects that the author has initiated during the last two decades, both involving combinatorial libraries of catalysts. The first encounter with combinatorial catalysis involved the use of a mixture of two different monodentate ligands in asymmetric transition metal catalysis, especially when one ligand is chiral and the other achiral. The reason for abandoning this approach as a research topic, although (industrially) successful, is outlined herein. The second and distinctly more significant approach concerns the directed evolution of stereo‐ and regioselective enzymes as catalysts in organic chemistry. It is not only a prolific source of catalysts for a variety of synthetically useful selective transformations, but has also produced several fundamentally important insights. The lessons learned include mechanistic intricacies of enzyme catalysis as well insights regarding cooperative mutational effects which are distinctly more than additive. The Darwinian approach to generating stereoselective enzymes is compared with evolution as it occurs in Nature.