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

Abstract

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 threestep 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

Parallel Synthesis and Screening of Polymer‐Supported Phosphorus‐Stereogenic Aminophosphane–Phosphite and –Phosphinite Ligands

“…The small difference in ee value between 22 and 23 can be attributed to matched/mismatched configurations of the phosphorus and the ephedrine moieties. [18] Combined with the decisive influence of substituent R 2 and the configuration of the P-atom, as established by the group of JugØ, [8] this information allows the rational design of highly efficient ligands.…”

“…P-stereogenic aminophosphane-phosphite and aminophosphane-phosphinite ligands (3, Scheme 1) have successfully been applied in asymmetric hydrogenation [8] and hydroformylation.…”

“…[6] Recently, we reported the solid-phase parallel synthesis of a variety of phosphites and phosphoramidites. [7] Herein, we report an efficient route for the parallel synthesis of polymer-supported phosphorus-stereogenic aminophosphane-phosphite and aminophosphane-phosphinite bidentate ligands, as well as their application in rhodium-catalyzed asymmetric hydrogenation.P-stereogenic aminophosphane-phosphite and aminophosphane-phosphinite ligands (3, Scheme 1) have successfully been applied in asymmetric hydrogenation [8] and hydroformylation. [9] As a result of the modular structure of this class of ligands, there is an enormous potential for ligand finetuning (R 1 , R 2 , and R 3 ), which makes them ideal candidates for the parallel synthesis of (supported) ligand libraries.However, these types of ligands have all been developed in the traditional synthetic way requiring troublesome and laborious ligand optimization.…”

“…A generally applicable combinatorial approach has not been developed yet because the synthetic methodology is still lacking. To assemble libraries of these chiral ligands the development of an efficient solidphase methodology is pivotal, not only to allow automated synthesis but also to circumvent work-up and purification problems, inherent to solution-phase synthesis.Following the general synthetic route developed by JugØ and co-workers (Scheme 1), [8] we developed the following route towards supported analogues. [10] The reaction of oxazaphospholidine borane 1 a (R 1 = phenyl) with the lithiated analogue 5 (Scheme 2) [11] of 4-bromo functionalized polystyrene 4 yielded a white resin that, based on the chemical shift of the relatively sharp resonance signal observed in its gel-phase 31 P NMR [12] spectrum (d = 71.4 ppm), was identified as 2 a (Scheme 2).…”

Synthesis of tervalent phosphorus esters in biphasic system using potassium phosphate as unique solid base

“…An original series of P-chirogenic aminophosphane-phosphinite (AMPP) ligands has been synthesized from (+)-or (−)-ephedrine. The AMPP ligands were used in the form of rhodium complexes for the catalyzed hydrogenation of α-acetamidocinnamate [8].…”