Zheng-Chao Duan

Enantioselective Synthesis of β2-Amino Acids via Rh-Catalyzed Asymmetric Hydrogenation with BoPhoz-Type Ligands: Important Influence of an N−H Proton in the Ligand on the Enantioselectivity

A series of BoPhoz-type ligands were successfully applied in the rhodium-catalyzed asymmetric hydrogenation of a number of beta-substituted or unsubstituted alpha-(phthalimidomethyl)acrylates, affording good to excellent enantioselectivities. The results suggested that the presence of an N-H proton in the BoPhoz backbone could significantly improve the enantioselectivity, and ligand (Sc,Rp)-1d, bearing two CF3-groups in the 3,5-position of the phenyl ring of aminophosphino moiety, showed the highest enantioselectivity.

Readily available chiral phosphine-aminophosphine ligands for highly efficient Rh-catalyzed asymmetric hydrogenation of alpha-enol ester phosphonates and alpha-enamido phosphonates.

A new class of unsymmetrical hybrid phosphine--aminophosphine ligands has been prepared from commercially available, inexpensive (S)-1-phenylethylamine through a concise synthetic procedure. These ligands are not very sensitive to air and moisture, and displayed good enantioselectivities in the Rh-catalyzed asymmetric hydrogenation of various dimethyl alpha-benzoyloxyethenephosphonates bearing beta-aryl, beta-alkyl, and beta-alkoxy substituents and N-benzyloxycarbonyl alpha-enamido phosphonates, in which up to 97% ee was obtained. A side-by-side comparison study disclosed that these new phosphine--aminophosphine ligands showed better enantioselectivity than BoPhoz ligands.

Enantioselective Synthesis of Chiral α-Aryl or α-Alkyl Substituted Ethylphosphonates via Rh-Catalyzed Asymmetric Hydrogenation with a P-Stereogenic BoPhoz-Type Ligand

An enantioselective synthesis of optically active 1-aryl or 1-alkyl substituted ethylphosphonates, based on the first Rh-catalyzed asymmetric hydrogenation of corresponding alpha,beta-unsaturated precursors with a P-stereogenic BoPhoz-type ligand under the mild condition, was developed, in which a wide range of 1-aryl or 1-alkyl substituted ethylphosphonates were achieved in up to 98% ee.

Highly Enantioselective Rh-Catalyzed Hydrogenation of β,γ-Unsaturated Phosphonates with Chiral Ferrocene-Based Monophosphoramidite Ligands

An enantioselective synthesis of chiral alkylphosphonates bearing a beta-stereogenic center, based on the Rh-catalyzed asymmetric hydrogenation of corresponding beta-substituted beta,gamma-unsaturated phosphonates with a ferrocene-based monophosphoramidite ligand under the mild hydrogenation conditions, was developed, in which an ee value of up to 98% was obtained.

Enantioselective Synthesis of β-Aryl-γ-amino Acid Derivatives via Cu-Catalyzed Asymmetric 1,4-Reductions of γ-Phthalimido-Substituted α,β-Unsaturated Carboxylic Acid Esters

A series of chiral beta-aryl-substituted gamma-amino butyric acid derivatives were synthesized in good enantioselectivities via the Cu-catalyzed asymmetric conjugate reduction of gamma-phthalimido-alpha,beta-unsaturated carboxylic acid esters using Cu(OAc)2 x H2O as a catalyst precursor, (S)-BINAP as a ligand, PMHS as a hydride source, and t-BuOH as an additive. The methodology has been applied successfully to the enantioselective synthesis of a chiral pharmaceutical, (R)-baclofen.

Enantioselective Rh-Catalyzed Hydrogenation of 3-Aryl-4-phosphonobutenoates with a P-Stereogenic BoPhoz-Type Ligand

A series of chiral 3-aryl-4-phosphonobutyric acid esters were synthesized in high enantioselectivities (93-98% ee) via the Rh-catalyzed asymmetric hydrogenation of the corresponding 3-aryl-4-phosphonobutenoates using a P-stereogenic BoPhoz-type phosphine-aminophosphine ligand. The methodology has been successfully applied to the asymmetric synthesis of a potential GABA(B) antagonist, (R)-phaclofen, in high enantioselectivity.