The increasing demand to produce enantiomerically pure pharmaceuticals, agrochemicals, flavors, and other fine chemicals has advanced the field of asymmetric catalytic technologies.1,2 Among all asymmetric catalytic methods, asymmetric hydrogenation utilizing molecular hydrogen to reduce prochiral olefins, ketones, and imines, have become one of the most efficient methods for constructing chiral compounds.3 The development of homogeneous asymmetric hydrogenation was initiated by Knowles4a and Horner4b in the late 1960s, after the discovery of Wilkinson’s homogeneous hydrogenation catalyst [RhCl(PPh3)3]. By replacing triphenylphosphine of the Wilkinson’s catalystwithresolvedchiralmonophosphines,6Knowles and Horner reported the earliest examples of enantioselective hydrogenation, albeit with poor enantioselectivity. Further exploration by Knowles with an improved monophosphine CAMP provided 88% ee in hydrogenation of dehydroamino acids.7 Later, two breakthroughs were made in asymmetric hydrogenation by Kagan and Knowles, respectively. Kagan reported the first bisphosphine ligand, DIOP, for Rhcatalyzed asymmetric hydrogenation.8 The successful application of DIOP resulted in several significant directions for ligand design in asymmetric hydrogenation. Chelating bisphosphorus ligands could lead to superior enantioselectivity compared to monodentate phosphines. Additionally, P-chiral phosphorus ligands were not necessary for achieving high enantioselectivity, and ligands with backbone chirality could also provide excellent ee’s in asymmetric hydrogenation. Furthermore, C2 symmetry was an important structural feature for developing new efficient chiral ligands. Kagan’s seminal work immediately led to the rapid development of chiral bisphosphorus ligands. Knowles made his significant discovery of a C2-symmetric chelating bisphosphine ligand, DIPAMP.9 Due to its high catalytic efficiency in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids, DIPAMP was quickly employed in the industrial production of L-DOPA.10 The success of practical synthesis of L-DOPA via asymmetric hydrogenation constituted a milestone work and for this work Knowles was awarded the Nobel Prize in 2001.3k This work has enlightened chemists to realize * Corresponding author. 3029 Chem. Rev. 2003, 103, 3029−3069

New Chiral Phosphorus Ligands for Enantioselective Hydrogenation

Supported chiral catalysts on inorganic materials

The new axially dissymmetric diphosphines (R)- and (S)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenyl phosphine) ((R)- and (S)-5a; ‘MeO-BIPHEP’) and the analogues (R)- and (S)-5b and 5c have been synthesized in enantiomerically pure form. These ligands have become readily available by a synthetic scheme which employs, as key steps, an ortho-lithiation/iodination reaction of the (m-methoxyphenyl)diprienylphosphine oxides 8 and a subsequent Ullmann reaction of the resulting iodides 9 to provide the racemic bis(phosphine oxides) 10. The bis(phosphine oxides) 10 subsequently are resolved with (−)-(2R,3R)- and (+)-(2S,3S)-O-2,3-dibenzoyltartaric acid and reduced to diphosphines 5. The Ullmann reaction constitutes a new and efficient route to 2,2′-bis(phosphinoyl)-substituted biphenyl systems. Absolute configurations were established for (R)-5a by X-ray analysis of the derived Pd complex (R,R)-17a, and for 5b and 5c by means of 1H-NMR comparisons of the derived Pd complexes 16 or 17, respectively, and by means of CD comparisons. The MeO-BIPHEP diphosphine 5a proved to be as efficient as the previously described BIPHEMP diphosphine ((6,6′-dimethylbiphenyl-2,2′-diyl)bis(diphenylphosphine)) in enantioselective isomerizations and hydrogenations.

Axially Dissymmetric Diphosphines in the Biphenyl Series: Synthesis of (6,6′‐Dimethoxybiphenyl‐2,2′‐diyl)bis(diphenylphosphine)(‘MeO‐BIPHEP’) and Analogues via an ortho‐Lithiation/Iodination Ullmann‐Reaction Approach

Recent advances in catalytic asymmetric reactions promoted by transition metal complexes

Dendrizymes: Expanded ligands for enantioselective catalysis

Racemisches Bicyclo[2.2.1]hept-5-en-2,3-diylbis(diphenylphosphan-oxid), Norphos, kann mit Hilfe von (−)-Di-O-benzoylweinsaure, (−)-DBW, optisch gespalten werden. Die Rontgenstrukturanalyse des in Ethanol schwerloslichen Diastereomeren (−)-Norphos/(−)-DBW zeigt starke Wasserstoffbrucken zwischen den Carboxylgruppen der DBW und den PO-Gruppierungen. Die Bindung der DBW-Carboxylgruppen an verschiedene Norphos-Einheiten fuhrt zur Ausbildung unendlicher dicht gepackter Ketten. Aus dem internen Vergleich mit (−)-DBW folgt fur (−)-Norphos die absolute Konfiguration (2R, 3R). Die durch SiHCl3-Reduktion von (+)-bzw. (−)- Norphos erhaltenen chelatbildenden Phosphane (+)-bzw. (−)-Norphos ergeben in neutralen und kationischen Rh-Komplexen bei der Hydrierung von α-(Acetylamino)zimtsaure, α-(Acetylamino)acrylsaure und Dopa-Vorstufen unter Normalbedingungen in wenigen Stunden quantitativ Aminosaurederivate mit optischen Ausbeuten zwischen 79 und 97%.



Asymmetric Catalyses, V. Enantioselective Amino Acid Synthesis by Hydrogenation of Prochiral Olefins with Rh-Complexes of the New Optically Active Chelating Phosphane Norphos



Racemic bicyclo[2.2.1]hept-5-en-2,3-diylbis(diphenylphosphane oxide), Norphos, can be resolved with (−)-di-O0-benzoyltartaric acid, (−)-DBW. The X-ray structure analysis of the diastereomer (−)-Norphos/(−)-DBW, which is less soluble in ethanol, exhibits strong hydrogen bonds between the carboxylic groups of DBW and the PO groups. The bonding of the DBW-carboxylic groups to different Norphos units leads to the formation of infinite close-packed chains. From the internal comparison with (−)-DBW the absolute configuration follows as (2R, 3R) for (−)-Norphos. The chelating phosphanes (+)-and (−)-Norphos, obtained by SiHCl3-reduction of (+)-and (−)-Norphos, respectively, afford neutral and cationic Rh-complexes which, with H2 at room temperature and atmospheric pressure within a few hours, give quantitative hydrogenation of α-(acetylamino)cinnamic acid, α-(acetylamino)acrylic acid and Dopa precursors. The optical yields very between 79 and 97%.

Asymmetrische Katalysen, V. Enantioselektive Aminosäuresynthese durch Hydrierung prochiraler Olefine mit Rh-Komplexen des neuen optisch aktiven chelatbildenden Phosphans Norphos

Sechs Zimtsaure- und Acrylsaure-Derivate, die sich nur in einem Substituenten unterscheiden, werden enantioselektiv zu den entsprechenden Phenylalanin- und Alanin-Derivaten hydriert. Als Katalysatoren dienen Mischungen aus [(1,5-COD)RhCl]2 und den optisch aktiven Phosphanen (−)-Norphos, (+)-Prophos, (+)-Diop und (−)-BPPFA. Die Auswertung der Ergebnisse mit der Ruch/Ugi-Theorie zeigt, das man auch bei Kenntnis der λ-Parameter der Substratsubstituenten und der p-Parameter der Katalysatoren die gefundenen Enantioselektivitaten nicht berechnen kann.



Asymmetric Catalyses, 11. Calculation of Enantioselectivities in the Rh-catalyzed Hydrogenation of Amino Acid Precursors with the Ruch/Ugi Model



Six cinnamic acid and acrylic acid derivatives, differing only in one substituent, were enantioselectively hydrogenated to give the corresponding phenylalanine and alanine derivatives. As catalysts mixtures of [(1,5-COD)RhCl]2 with the optically active phosphanes (−)-Norphos, (+)-Prophos, (+)-Diop, and (−)-BPPFA were used. The analysis of the results with the Ruch/Ugi theory shows that, even knowing the λ-parameters of the substrate substituents and the p-parameters of the catalysts, the enantioselectivities found cannot be calculated.

Asymmetrische Katalysen, 11. Vorausberechnung von Enantioselektivitäten bei der Rh‐katalysierten Hydrierung von Aminosäure‐Vorläufern mit dem Ruch/Ugi‐Modell

Amidinato complexes with substituents R at the cyclopentadienyl and R′ in the p-position of the phenyl at the asymmetric C atom were synthesized and characterized. The diastereomers differing in their 1H NMR spectra were partly separated by fractional crystallization. After equilibration with respect to the labile Mo configuration the diastereomer ratio, a measure for the asymmetric induction from the chiral ligand on the formation of the two Mo configurations at equilibrium, was determined by 1H NMR integration. The diastereomer ratio decreases for substituents R′ = F and R = CH3, and increases for R' = OCH3, compared to the unsubstituted compound.

Optisch aktive Übergangsmetall-Komplexe, 84 [1] Substituenten-Effekte in Diastereomerengleichgewichten von quadratisch-pyramidalen Mo-Komplexen / Optically Active Transition Metal Complexes, 84 [1] Substituent Effects in Diastereomer Equilibria of Square-Pyramidal Mo Complexes

Beate Schönhammer

Papers

Asymmetrische Katalysen, V. Enantioselektive Aminosäuresynthese durch Hydrierung prochiraler Olefine mit Rh-Komplexen des neuen optisch aktiven chelatbildenden Phosphans Norphos

Asymmetrische Katalysen, 11. Vorausberechnung von Enantioselektivitäten bei der Rh‐katalysierten Hydrierung von Aminosäure‐Vorläufern mit dem Ruch/Ugi‐Modell

Optisch aktive Übergangsmetall-Komplexe, 84 [1] Substituenten-Effekte in Diastereomerengleichgewichten von quadratisch-pyramidalen Mo-Komplexen / Optically Active Transition Metal Complexes, 84 [1] Substituent Effects in Diastereomer Equilibria of Square-Pyramidal Mo Complexes