17404-43-2Relevant academic research and scientific papers
Improved Synthesis of MediPhos Ligands and Their Use in the Pd-Catalyzed Enantioselective N-Allylation of Glycine Esters
Albat, Dominik,Neud?rfl, J?rg-Martin,Reiher, Martin,Schmalz, Hans-Günther
, p. 4237 - 4242 (2021/08/24)
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.
