Simple Open-Chain Phosphite-Olefin as Ligand for Rh-Catalyzed Asymmetric Arylation of Cyclic Ketimines: Enantioselective Access to gem-Diaryl α-Amino Acid Derivatives

Abstract

A new class of open-chain chiral phosphite-based hybrid olefin ligands has been developed and utilized in Rh-catalyzed asymmetric arylation of 1,2,5-thiadiazolidine 1,1-dioxide type cyclic ketimines. The reactions generate quaternary carbon-containing, gem-diaryl-substituted sulfahydantoins and 4-ethoxy-2,3-dihydro-1,2,5-thiadiazole 1,1-dioxides with excellent enantioselectivities under exceptionally mild and user-friendly conditions using a H8-binol-derived phosphite-olefin ligand. The method is useful in offering efficient and convenient synthesis of enantioriched α,α-diaryl-α-amino acid amides and nitrogen-containing heterocycles. Furthermore, by taking advantage of the protocol, the first enantioselective synthesis of BACE1 inhibitor (R)-iminohydantoin has been accomplished.