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

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.