title: Catalytic, asymmetric, and stereodivergent synthesis of non-symmetric β,β-diaryl-α-amino acids.
abstract: 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.
authors.affiliation: Department of Process Chemistry, Merck & Co. Inc. , Rahway, New Jersey 07065, United States.
authors.forename: Carmela
authors.initials: C
authors.lastname: Molinaro
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Scott
authors.forename: Michael
authors.initials: M
authors.lastname: Shevlin
authors.forename: Christopher
authors.initials: C
authors.lastname: Wise
authors.forename: Alain
authors.initials: A
authors.lastname: Ménard
authors.forename: Andrew
authors.initials: A
authors.lastname: Gibb
authors.forename: Ellyn M
authors.initials: EM
authors.lastname: Junker
authors.forename: David
authors.initials: D
authors.lastname: Lieberman
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D006865:Hydrogenation; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids