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.

A new class of chiral C2‐symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd‐catalyzed asymmetric N‐allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional SN2‐coupling of a tartrate‐derived ditosylate with 6‐alkyl‐2‐bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd‐catalyzed N‐allylation of tert‐butyl glycinate with racemic (E)‐2,8‐dimethylnona‐5‐en‐4‐yl methyl carbonate (up to 95 % ee). In addition, the analogous transformation of tert‐butyl glycinate with methyl (E)‐nona‐5‐en‐4‐yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline‐derived dipeptide analogs ProM‐17 and ProM‐21.

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