Chiral Bicyclic Phosphoramidites—A New Class of Ligands for Asymmetric Catalysis

Abstract

The development of new ligands for catalytic asymmetric C−C bond formation is of great interest to organic synthesis. We describe here a new class of chiral phosphoramidites that embody one or two binaphthol units attached to an achiral azabicyclic [3.3.1] or [3.3.0] framework. These ligands were easily accessible from (R)-1,1′-binaphthyl-2,2′-dioxaphosphorchloridite (4) and the corresponding heterobicyclic core 1, 2, or 3. They were employed in enantioselective Cu-catalyzed additions of different dialkylzinc reagents to cyclic and acyclic enones. The chiral ketones were obtained with an enantiomeric ratio up to 91:9. The choice of the best ligand proved to be strongly dependent on each substrate. In addition, ligand 6 was found to be the most suitable for Rh-catalyzed hydrogenations of α,β-unsaturated esters, giving rise to dimethyl 2-methylsuccinate and methyl N-acetylalaninate with enantiomer ratios up to 95:5.