A Strategy for the Stereoselective Synthesis of Unsymmetric Atropisomeric Ligands: Preparation of NAPhePHOS, a New Biaryl Diphosphine

MeO‐NAPhePHOS represents the first example of a new series of atropisomeric diphosphines bearing heterotopic biaryl moieties. The key step of its synthesis is the diastereoselective, intramolecular, CuI‐promoted coupling of 1‐iodonaphthol and 2‐iodo‐3‐methoxyphenol connected by a chiral tether. (R,R)‐2,4‐Pentanediol is used as the chiral auxiliary in this highly selective reaction that leads to a single enantiomer of the title diphosphine. In the Ru‐promoted hydrogenations of carbonyl derivatives, NAPhePHOS affords enantioselectivity levels fully comparable to those of the C2‐symmetrical analogues, BINAP and MeO‐BIPHEP respectively, thus showing that the lack of C2 symmetry is not detrimental to the catalytic properties of atropisomeric ligands in these hydrogenation reactions. The highly stereoselective, intramolecular formation of the aryl–aryl bond is the key step of an efficient strategy for the synthesis of atropisomeric diphosphines, such as (S)‐MeO‐NAPhePHOS (see picture), bearing heterotopic aryl moieties.