Backdoor Induction of Chirality in Asymmetric Hydrogenation with Rhodium(I) Complexes of Amino Acid Substituted Triphenylphosphane Ligands

This paper describes the synthesis and characterization of 5-(diphenylphosphanyl)isophthalic acid bioconjugates (Lig-[R](2)). In addition to symmetrically disubstituted conjugates with amino acids, peptides or amines, a convenient one-pot, two-step procedure for the synthesis of conjugates bearing two different substituents is reported. The 28 prepared phosphanes were used as monodentate ligands in the rhodium(I)-catalyzed hydrogenation of 2-acetamidoacrylate and (Z)--acetamidocinnamate. The ligand with the smallest side-chain substituents Lig-[Ala-OMe](2) (1a) revealed the highest selectivity, with up to 84% ee. The catalysts presented herein are models of artificial metalloenzymes in which the outer-coordination sphere controls the selectivity in catalysis. The chirality of distant hydrogen-bonded amino acids is transmitted by backdoor induction to the prochiral Rh-I center.