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RESEARCH PRODUCT

Modular P-Chirogenic Aminophosphane-Phosphinite Ligands for Rh-Catalyzed Asymmetric Hydrogenation: A New Model for Prediction of Enantioselectivity

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An original series of P-chirogenic aminophosphane-phosphinite (AMPP) ligands has been synthesized from (+)- or(–)-ephedrine in 23 to 61 % overall yields by a versatile three-step methodology. The AMPP ligands, bearing either one or two P-chirogenic centers, were used in the form of rhodium complexes for the catalyzed hydrogenation of α-acetamidocinnamate as a test reaction. Notably, even with AMPP ligands all derived from (+)-ephedrine, variation of the substituent on a P-center allowed the phenylalanine derivatives to be obtained in either (S) or (R) absolute configurations, with ee values ranging from 99 % (S) to 88 % (R). The asymmetric induction was analyzed with the aid of X-ray structures of AMPP complexes, and a new model for the enantioselectivity, taking into consideration the boat conformation and the steric and electronic dissymmetries at the dihydride rhodium-substrate complex, has been proposed. This model offers an alternative to the quadrant rule, well adapted to the C2-symmetry ligands and the chair conformation of their complex derivatives. In this work, the model, which schematizes the front side of the complex as a sextant in the direction of the cardinal points, fits with coordination of the substrate by the acetamido and the cinnamyl groups in the north and east (or west) parts, respectively. The enantioselectivity originates from the ligand residues located at the south-east or south-west parts of the dihydride rhodium intermediate. Computer modeling on several AMPP-rhodium complexes with PCModel confirms the proposed predicting model.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)