Controlling the Enantioselectivity in an Adaptable Ligand by Biomimetic Intramolecular Interlocking

For the preparation of chiral drugs, both stereochemically stable and flexible catalysts in combination with chiral auxiliaries can be used. Here, chiral induction plays an important role in generating an enantiomerically pure catalyst. We demonstrate a successful approach to the spontaneous deracemization of tropos ligands for asymmetric catalysis. Three different constitutional isomers of a bisphosphinite ligand decorated with l-valine moieties (interaction units) linked to the flexible biphenyl system by a phenylene bridge for inducing a chiral switch were prepared. The substitution pattern's influence on the attached intermolecular recognition sites was systematically investigated. We can show that biomimetic intramolecular hydrogen bonding leads to a pronounced diastereoselective enrichment of one of the ligand stereoisomers. As a result, in the asymmetric Rh-catalyzed hydrogenation of prochiral olefins using these ligands, enantiomeric ratios of up to 95.8:4.2 (S) were obtained. Of particular note is the inversion of enantioselectivity relative to the previously reported BIBIPHOS-Rh catalyst due to the altered orientation of the biphenyl moiety from (R_ax) to (S_ax). The enantioselectivities achieved by appropriate intramolecular interlocking are remarkable for a tropos ligand/catalyst. The strategy presented here represents a powerful approach for the spontaneous alignment of tropos ligands, yielding high enantioselectivities in asymmetric catalysis.