New chiral ferrocenyl P,S-ligands for highly diastereo-/enantioselective catalytic [3 + 2] cycloaddition of azomethine ylides with cyclic and acyclic enones.

A new family of chiral ferrocenyl P,S-ligands has been developed and successfully applied in a highly endo-selective catalytic asymmetric cycloaddition of azomethine ylides with various enones, including cyclic and acyclic α-enones. For cyclic α-enones, a [Cu(CH(3)CN)(4)]ClO(4)/(R(c),S(Fc))-2f complex catalyzed the cycloaddition to give the sole endo-cycloadducts in perfect enantioselectivities (normally 99% ee), while an AgOAc/(R(c),S(Fc))-2f catalytic system exhibited good endo/exo selectivities (endo/exo = 91/9 to 96/4) and high enantiocontrol (up to 98% ee) for acyclic α-enones.

Highly enantioselective Rh-catalyzed hydrogenation of beta,gamma-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 Rh-catalyzed hydrogenation of 3-aryl-2-phosphonomethylpropenoates by a new class of chiral ferrocenyl diphosphine ligands.

A new class of chiral ferrocenyl diphosphine ligands with an imidazole ring, (R(c),S(Fc))-ImiFerroPhos, has been prepared from acylferrocenes through a five-step transformation and successfully applied in the Rh-catalyzed asymmetric hydrogenation of various 3-aryl-substituted 2-phosphonomethylpropenoates, in which a series of chiral 3-phosphono-2-arylmethylpropanoic acid derivatives were achieved in ee values of up to 98%.

Enantioselective synthesis of chiral alpha-aryl or alpha-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.

Enantioselective synthesis of beta-aryl-gamma-amino acid derivatives via Cu-catalyzed asymmetric 1,4-reductions of gamma-phthalimido-substituted alpha,beta-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.

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 beta2-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.

Rh-catalyzed asymmetric hydrogenation of gamma-phthalimido-substituted alpha,beta-unsaturated carboxylic acid esters: an efficient enantioselective synthesis of beta-aryl-gamma-amino acids.

A series of chiral beta-aryl-gamma-amino acid ester derivatives were synthesized in high enantioselectivities (93-97% ee) via the Rh-catalyzed asymmetric hydrogenation of gamma-phthalimido-alpha,beta-unsaturated carboxylic acid esters using highly modular chiral BoPhoz-type phosphine-aminophosphine ligands. The method has been applied successfully to the synthesis of several chiral pharmaceuticals including (R)-baclofen and (R)-rolipram with high enantioselectivities.

Readily available phosphine-phosphoramidite ligands for highly efficient Rh-catalyzed enantioselective hydrogenations.

A new family of air- and moisture-stable phosphine-phosphoramidite ligands (PEAPhos) has been prepared from commercially available and inexpensive (S)-alpha-phenylethylamine through a two- or three-step transformation and successfully applied in the rhodium-catalyzed enantioselective hydrogenations of a variety of substrates, in which up to 99.9% ee was obtained for all of these kinds of substrates.