Rhodium-catalyzed asymmetric hydrogenation using self-assembled chiral bidentate ligands*

The chirality-directed self-assembly of bifunctional subunits around a structural metal—typically, zinc(II)—is used to form a heteroleptic complex in which a second set of ligating groups are suitably disposed to bind a second metal, forming a heterobimetallic cat- alyst system. We find that subtle changes in the structural backbone (i.e., ligand scaffold) of such chiral bidentate self-assembled ligands (SALs) can be used to manipulate the ligand topography and chiral environment around catalytic metal; thus, the scaffold can be opti- mized to maximize asymmetric induction. Using this combinatorial strategy for ligand syn- thesis, a preliminary study was carried out in which a library of 110 SALs was evaluated in the rhodium-catalyzed asymmetric hydrogenation of a simple N-acyl enamide. The level of enantioselectivity obtained varies from near racemic to greater than 80 % ee as a function of the ligand scaffold, with the possibility of further improvement yet to be explored.