Catalytic, Asymmetric, and Stereodivergent Synthesis of Non-Symmetric β,β-Diaryl-α-Amino Acids

We
report a concise, enantio- and diastereoselective route to novel
nonsymmetrically substituted N-protected β,β-diaryl-α-amino
acids and esters, through the asymmetric hydrogenation of tetrasubstituted
olefins, some of the most challenging examples in the field. Stereoselective
generation of an E- or Z-enol tosylate,
when combined with stereoretentive Suzuki-Miyaura cross-coupling and
enantioselective hydrogenation catalyzed by (NBD)2RhBF4 and a Josiphos ligand, allows for full control over the two
vicinal stereogenic centers. High yields and excellent enantioselectivities
(up to 99% ee) were obtained for a variety of N-acetyl, N-methoxycarbonyl, and N-Boc β,β-diaryldehydroamino
acids, containing a diverse and previously unreported series of heterocyclic
and aryl substituted groups (24 examples) and allowing access to all
four stereoisomers of these valuable building blocks.