Access to Planar- and P-Chiral Macrocyclophane-Based Phosphines via Palladium-Catalyzed Asymmetric Hirao Reaction

Abstract

Notable advances have been made in the catalytic asymmetric fabrication of chiral phosphine oxides. Nevertheless, the asymmetric synthesis of phosphine oxides integrated in a planar-chiral macrocyclophane remains unexplored, which is ascribed to the conformational flexibility of the macrocycle. Reported herein is a Pd-catalyzed asymmetric Hirao reaction that utilizes nonaflate-functionalized macrocyclophanes as substrates. By employing achiral secondary phosphine oxides (SPOs) as the coupling partner, planar-chiral phosphorylated macrocyclophanes were accessed via kinetic resolution. In the case of chiral, racemic SPO reagents, integrated planar- and P-chiral macrocyclophanes were accessed via kinetic resolution of the cyclophane but dynamic kinetic resolution of the SPO. Both coupling systems proceeded under unified reaction conditions with good functional group tolerance and efficient asymmetric control. Derivatizations and catalytic applications highlighted the synthetic applicability and potential of the planar-chiral scaffold in asymmetric synthesis and catalysis.