Pd-Catalyzed Asymmetric N-Allylation of Amino Acid Esters with Exceptional Levels of Catalyst Control: Stereo-Divergent Synthesis of ProM-15 and Related Bicyclic Dipeptide Mimetics |
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Authors: | Dr. Stephan Dohmen Dr. Martin Reiher Dominik Albat Dr. Sema Akyol Dr. Matthias Barone Dr. Jörg-Martin Neudörfl Dr. Ronald Kühne Prof. Dr. Hans-Günther Schmalz |
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Affiliation: | 1. Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Köln, Germany;2. Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany |
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Abstract: | A general and powerful method for the stereo-controlled Pd-catalyzed N-allylation of amino acid esters is reported, as a previously largely unsolved synthetic challenge. Employing a new class of tartaric acid-derived C2-symmetric chiral diphosphane ligands the developed asymmetric amination protocol allows the conversion of various amino acid esters to the N-allylated products with highest levels of enantio- or diastereoselectivity in a fully catalyst-controlled fashion and predictable configuration. Remarkably, the in situ generated catalysts also exhibit outstanding levels of activity (ligand acceleration). The usefulness of the method was demonstrated in the stereo-divergent synthesis of a set of new conformationally defined dipeptide mimetics, which represent new modular building blocks for the development of peptide-inspired bioactive compounds. |
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Keywords: | asymmetric catalysis chiral diphosphine ligands peptide mimetics protein interactions transition-metal catalysis |
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