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The Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands has been developed. Under the optimized conditions, a wide range of β-keto esters were hydrogenated to afford the corresponding β-hydroxy esters in good to excellent enantioselectivities (up to 95% ee).

Highly diastereo- and enantioselective copper-catalyzed propargylic alkylations of propargylic acetates with morpholine-derived cyclic enamines for the construction of vicinal tertiary stereocenters have been developed. By the employment of a less sterically hindered chiral tridentate P,N,N-ligand, good to excellent diastereo- (up to >98 : 2 dr) and enantioselectivity (up to 99% ee) could be achieved for a wide range of substrates.

The asymmetric hydrogenation of N-arylimines with the chiral phosphine-phosphoramidite ligand, (Sc,Sa)-PEAPhos 2b, has been developed. The results revealed that the presence of the substituents on the 3,3′-positions of the binaphthyl backbone significantly improved the enantioselectivity. The utility of this methodology was demonstrated in the synthesis of the chiral fungicide (R)-metalaxyl.

A copper-catalyzed [3 + 2] cycloaddition of propargylic esters with β-enamino esters under mild reaction conditions for the construction of highly functionalized pyrroles has been developed. By employment of a newly developed tridentate P,N,N-ligand, a variety of fully substituted pyrroles were achieved in good to high yields.

The copper-catalyzed propargylic substitution reaction has become a powerful synthetic method to prepare the compounds containing the propargylic subunit. Compared with the other transition-metals applied in the propargylic substitution, copper has many obvious advantages, such as much more inexpensive, easier to handle, milder reaction condition, and higher selectivity. This digest summarizes the recent development in the copper-catalyzed propargylic substitutions with various nitrogen, carbon, oxygen, and sulfur nucleophiles. In addition, the cycloadditions involving the copper-catalyzed propargylic substitution as the key step are included.

A copper-catalyzed domino cyclization of propargylic alcohols with tosyl isocyanate for the synthesis of oxazolidinones has been developed. Various propargylic alcohols with an aryl or alkyl substituents worked smoothly to afford the corresponding oxazolidinones in moderate to excellent yields.

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.

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.

A series of novel chiral phosphine–imine ligands have been prepared by a two-step transformation from chiral α-phenylethylamine. The resulting chiral ligands were found to be effective for the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenylprop-2-en-1-yl pivalate with dimethyl malonate, in which up to 94% ee and 99% conversions were obtained. The results demonstrate that the chirality resided on the chelate ring of P–Pd–N complex is more effective for the transfer of the stereochemical information by comparison with the result obtained by Hashimoto and coworkers’ phosphine–imine ligand, in which the chirality lay in the outside of P–Pd–N chelate ring. The effect of solvent, base and substitutent in phosphine–imine ligand on this catalytic reaction is also described.

[reaction: see text] A new family of unsymmetrical ferrocenylethylamine-derived monophosphoramidites were synthesized and successfully applied in the Rh-catalyzed enantioselective hydrogenation of a range of enamides and alpha-dehydroamino acid esters, and ee values of up to 99.5% were obtained for both types of substrate. These results suggest that unsymmetrical amine-derived monophosphoramidites can also exhibit excellent enantioselectivity for a broad range of substrates, comparable to or higher than those of the most efficient symmetrical amine-derived monophosphoramidites reported thus far.

[reaction: see text] Excellent enantioselectivities and high turnovers (S/C = 5000) were achieved in the Rh(I)-catalyzed asymmetric hydrogenation of both beta-aryl- and beta-alkyl-beta-(acylamino)acrylates with a new unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligand, and the presence of an N-H proton in the ligand was demonstrated to have a crucial role in the enantioselectivity.

Chiral ferrocene-based phosphine-imine ligands 1-3 and sulfur-imine ligand 4 were applied in the palladium-catalyzed asymmetric allylic alkylation of cycloalkenyl esters. The results revealed that the substitutents in aryl ring, ferrocenylmethyl and benzyliene position strongly affected the enantioselective induction of phosphine-imine ligands, and the most stereoselective ligand was ferrocenylphosphine-imine 1b with a nitro group in the meta-position of phenyl ring. Under the optimized condition, up to 91% (enantiomeric excesses) e.e. of cyclic alkylation product was obtained by the use of 1b. (C) 2004 Elsevier B.V. All rights reserved.

Novel chiral P,N,N-type ligands ( 4 ) derived from ( R )-( S )-PPFNH 2 -R ( 6 ) and 2-pyridinecarboxaldehydes were employed in Ru(II)-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate. Up to 99% yield with 95% e.e. for cis -isomer and 90% e.e. for trans -isomer was obtained on Ru(II)/ 4a .

New chiral ferrocenyldiphosphine ligands (R)-(S)-3 and (R)-(S)-4 were prepared. The ligands were employed in Ru(II) catalyzed asymmetric transfer hydrogenation of ketones to give corresponding secondary alcohols. Up to 99% conversion with 90% e.e. was obtained on Ru(DMSO)(4)Cl-2/4 in transfer hydrogenation of acetophenones with propan-2-ol. (C) 2003 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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.

[reaction: see text] The synthesis and application of a new family of air-stable, highly unsymmetrical ferrocene-based phosphine-phosphoramidites is described. The new ligands exhibit excellent enantioselectivities (over 99% ee) in the Rh-catalyzed asymmetric hydrogenation of enamides, dimethyl itaconate, and methyl (Z)-acetamidocinnamate even with high catalyst turnovers (S/C=10,000). The binaphthyl moiety is crucial for reactivity and enantioselectivity, and its absolute configuration plays a dominant role in determining the chirality of the hydrogenation products.

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.