Combinations of a binaphthol-derived phosphite and a C1-symmetric phosphinamine generates heteroleptic catalysts in Rh- and Pd-mediated reactions

In recent years, monodentate phosphorus ligands (e.g. phosphites, phosphonites, phosphoramidites and phosphinamines) have held the stage in asymmetric catalysis. The modular nature of all these ligands allows the synthesis of a wide variety of representatives, thereby making a combinatorial approach possible. An important breakthrough in this area was made independently by the groups of Reetz and Feringa, who used a binary mixture of chiral monodentate P-ligands in several asymmetric rhodium catalysed reactions. By mixing two ligands (La and Lb) in the presence of Rh, three species can be formed: RhLaLa, RhLbLb (homocomplexes), and RhLaLb (heterocomplex). The heterocombination is often more reactive and more (regio-, diastero- and enantio-) selective than either of the two homocombinations. The ideal case would constitute an equilibrium completely in favour of the heterocomplex [RhLaLb] because then only a single well-defined catalyst would exist in the reaction, and the undesired competition of the less selective homocomplexes would be avoided. The 1:1 mixture of a chiral phosphite with an achiral phosphine was reported to induce reversal of the enantioselectivity in the Rh-catalysed hydrogenation of N-acetamido acrylate (compared to the chiral phosphite alone). The only possible explanation for this peculiar behaviour is the selective formation of the phosphite-phosphine Rh-heterocomplex, favoured by electronically matching one sigma-donor ligand (phosphine) and one pigreca-acceptor ligand (phosphite). For this reason we investigated the use of combinations of phosphites with phosphinamines for the selective formation of rhodium heterocomplexes. DFT calculations showed that the phosphite-phosphinamine rhodium heterocomplex is more stable than the two homocomplexes by 11.29 kcal/mol. A small library of enantiomerically pure phosphites and phosphinamines was prepared and complexation studies were performed by means of 31PNMR, using Rh(acac)(C2H4)2 as the rhodium source. When C1-symmetric phosphinamine ligands were employed, the cis-heterocomplexes were formed with selectivities ranging from moderate (70%) to excellent (≥99%). The homo- and heterocombinations of phosphites and of the C1-symmetric phosphinamines were then screened in the rhodium-catalysed hydrogenation of methyl 2-acetamidoacrylate and in the palladium-catalysed asymmetric allylic substitution of rac-1,3-diphenyl-3-acetoxyprop-1-ene with dimethyl malonate. Remarkably, the 1:1 combination of a binol-derived phosphite and a phosphinamine induced reversal of the enantioselectivity and, in the case of the palladium-catalysed asymmetric allylic substitution, also a modest increase of the enantioselectivity.