1. 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
- Author
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Stephan Dohmen, Martin Reiher, Ronald Kühne, Dominik Albat, Jörg-Martin Neudörfl, Matthias Barone, Sema Akyol, and Hans-Günther Schmalz
- Subjects
Models, Molecular ,Proline ,Crystallography, X-Ray ,Ligands ,010402 general chemistry ,protein interactions ,01 natural sciences ,Catalysis ,chemistry.chemical_compound ,chiral diphosphine ligands ,Diphosphane ,Amino Acids ,Peptide Mimetics ,transition-metal catalysis ,Amination ,chemistry.chemical_classification ,Alanine ,Dipeptide ,Cycloaddition Reaction ,Molecular Structure ,Bicyclic molecule ,010405 organic chemistry ,Communication ,organic chemicals ,Organic Chemistry ,Enantioselective synthesis ,asymmetric catalysis ,Esters ,Stereoisomerism ,Dipeptides ,General Chemistry ,Combinatorial chemistry ,Communications ,0104 chemical sciences ,Amino acid ,chemistry ,Oxidation-Reduction ,Divergent synthesis ,Palladium - 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 C 2‐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., Identification of a powerful ligand for the catalytic asymmetric N‐allylation of amino acid esters paved the way for a short and fully stereo‐controlled access to new dipeptide building blocks with a defined 3D structure (see scheme).
- Published
- 2020
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