Chiral iridium(I) bis(NHC) complexes as catalysts for asymmetric transfer hydrogenation

The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L ‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley & Sons, Ltd.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Highly efficient iridium catalyst for asymmetric transfer hydrogenation of aromatic ketones under base-free conditions

[reaction: see text] Catalytic systems generated in situ from the chiral PNNP ligands with iridium or rhodium hydride complexes exhibited excellent catalytic activity and good enantioselectivity in the asymmetric transfer hydrogenation of aromatic ketones without added base. The best result was obtained in the IrH(CO)(PPh(3))(3)-ligand 2 catalytic system with up to 99% yield and 97% ee.     

Chiral quinolinyl-oxazolines as ligands for copper(I)-catalyzed asymmetric cyclopropanation

Chiral quinolinyl-oxazoline compounds have been synthesized from enantiomerically pure amino alcohols and 8-quinoline-carboxylic acid using a convenient procedure. Asymmetric cyclopropanation of styrene with diazoacetates in the presence of 1 mol% of CuOTf and quinolinyl-oxazolines gave 2-phenylcyclopropane carboxylates in moderate enantiomeric excesses.     

2-Azanorbornyl alcohols: very efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic ketones

2-Azanorbornyl-derived amino alcohols were prepared and evaluated as ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. To improve selectivity and rate, the structure of the ligand was optimized. Acetophenone was reduced using 0.5 mol % catalyst in 40 min in 94% ee. This system was also able to reduce a wide range of aromatic ketones to the corresponding alcohols, while maintaining high enantioselectivities and yields. The effects of catalyst loading and the presence of cosolvents in the reaction vessel were examined, and a linearity study was also done.     

Accelerated asymmetric transfer hydrogenation of aromatic ketones in water

Asymmetric transfer hydrogenation of various simple aromatic ketones by the Ru-TsDPEN catalyst was shown to be feasible in aqueous HCOONa without calling for any catalyst modification, furnishing ee's of up to 95% and significantly faster rates than in the HCOOH-NEt(3) azeotrope.     

Chiral porous hybrid solids for practical heterogeneous asymmetric hydrogenation of aromatic ketones

Chiral porous zirconium phosphonates containing Ru-BINAP-DPEN moieties were synthesized via a molecular building-block approach, and characterized by a variety of techniques including TGA, adsorption isotherms, XRD, SEM, IR, and microanalysis. These hybrid solids were used for enantioselective heterogeneous asymmetric hydrogenation of aromatic ketones with remarkably high ee values of up to 99.2%. These solid catalysts can also be easily recycled and reused for eight times without the loss of activity and enantioselectivity. Ready tunability of such a molecular building-block approach will allow the optimization of these hybrid materials and promise to lead to other practically useful heterogeneous asymmetric catalysts.     

8-Amino-5,6,7,8-tetrahydroquinolines as ligands in iridium(III) catalysts for the reduction of aryl ketones by asymmetric transfer hydrogenation (ATH)

Aqua iridium(III) complexes with 8-amino-5,6,7,8-tetrahydroquinolines CAMPY L1 and its derivatives as chiral ligands proved to be very efficient catalysts for the reduction of a wide range of prochiral aryl ketones, revealing a variety of behaviours in terms of reaction rate and stereoselectivity. As standard substrates, differently substituted acetophenones were studied and good enantioselectivity (86% ee) was achieved in the reduction of 1-(o-tolyl)ethan-1-one 6. Particularly interesting was the ATH reaction in the case of β-amino keto esters, precursors of β-lactams and azetidinones. The best results were obtained with [Cp¹Ir(H₂O)(L1)]SO₄ affording the corresponding diastereomeric alcohols in an (R,S)-configuration with an excellent 99% ee in the reduction of 2-(benzamido methyl)-3-oxo-3-(4-(trifluoromethyl)phenyl)propanoate 12.     

Enantioselective transfer hydrogenation catalyzed by iridium(I) complexes with nitrogen donor ligands

The reduction of prochiral ketones by hydrogen transfer from isopropanol is catalyzed by cationic iridium(I) complexes containing optically active Schiff bases. Optical yields of up to 33% have been obtained.     

Highly efficient Rh(I)-catalyzed asymmetric hydrogenation of enamines using monodente spiro phosphonite ligands

A highly enantioselective hydrogenation of nonfunctionalized enamines has been developed by using rhodium complexes of chiral spiro phosphonite ligands, providing chiral tertiary amines in excellent enantioselectivities.     

Chiral monodentate phosphorus ligands for rhodium-catalyzed asymmetric hydrogenation

This review reports the recent developments in the field of asymmetric hydrogenation in the presence of metal catalysts containing monodentate phosphorus ligands. Besides monophosphines, that have been used at the origin of asymmetric hydrogenation, it mainly includes the use of monophosphites and monophosphoramidites, which when associated to rhodium precursors have recently led to very efficient enantioselective catalytic systems.     

A modular design of ruthenium(II) catalysts with chiral C2-symmetric phosphinite ligands for effective asymmetric transfer hydrogenation of aromatic ketones

Hydrogen-transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity. The new chiral C₂-symmetric ligands N,N′-bis-[(1S)-1-sec-butyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 1 and N,N′-bis-[(1S)-1-phenyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 2 and the corresponding ruthenium complexes 3 and 4 have been prepared and their structures have been elucidated by a combination of multi-nuclear NMR spectroscopy, IR spectroscopy, and elemental analysis. ¹H–³¹P NMR, DEPT, ¹H–¹³C HETCOR, or ¹H–¹H COSY correlation experiments were used to confirm the spectral assignments. The catalytic activity of complexes 3 and 4 in transfer hydrogenation of acetophenone derivatives by iso-PrOH has also been studied. Under optimized conditions, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as excellent catalysts, giving the corresponding chiral alcohols in 99% yield and up to 75% ee. This transfer hydrogenation is characterized by low reversibility under these conditions.     

Efficient Ru(II)-catalyzed asymmetric hydrogenation of simple ketones with C2-symmetric planar chiral metallocenyl phosphinooxazoline ligands

C₂-symmetric metallocenyl planar phosphinooxazoline ligands (2 and 3) have been applied in the Ru(II)-catalyzed asymmetric hydrogenation of simple ketones. This type of ligands enjoys the advantages of dual reaction sites as well as larger steric hindrance than their corresponding C₁-symmetric counterparts. As a result, almost quantitative conversions and excellent enantioselectivities were obtained for a series of simple ketones. Under the optimal reaction conditions, up to 99.7% ee was obtained in many cases. It was also confirmed that hydrogen rather than reaction solvent i-PrOH is at work in the hydrogenation procedure.     

Highly efficient chiral PNNP ligand for asymmetric transfer hydrogenation of aromatic ketones in water

Chiral PNNP ligand II and [IrHCl₂(COD)]₂ were applied for the first time in the asymmetric transfer hydrogenation of aromatic ketones with HCOONa in water, giving the corresponding optical alcohols in high yield and excellent enantioselectivity (up to 99% ee). Particularly, the reduction of propiophenone proceeded smoothly at a substrate to catalyst molar ratio of 8000, without compromising the ee values obtained.     

手性双胺双膦-铱体系催化芳香酮的高对映选择性氢转移氢化

在异丙醇溶液中,从[Ir(COD)Cl]2和C2-对称的手性双胺双膦配体原位制备了手性能-Ir(Ⅰ)配合物,并直接用于催化几种芳香酮的不对称氢转移氢化。结果表明,该配合物是异丙基苯基酮不对称转移氢化的优秀催化剂,当底物酮与催化剂的摩尔比(S/C)为1200:1时,在室温下反应4h后,得到相应的手性芳香醇的转化率和对映选择性分别高达98%和98%ee.     

Manganese catalyzed asymmetric transfer hydrogenation of ketones

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral P_xN_y-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)₅] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP₂N₄ (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.     

Asymmetric transfer hydrogenation of aromatic ketones by Rh(I)/bimorpholine complexes

The asymmetric hydride transfer reduction of aromatic ketones, using a [Rh(cod)Cl]₂ complex as a catalyst and (3S,3′S)-bimorpholine as a chiral ligand, was studied. By varying the amount of ligand, basic co-catalyst and temperature, high yields (>90%) and good enantiomeric excesses of the alcohols (ee up to 83%) were achieved.