Chiral sulfur-containing ligands for iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones

New efficient catalyst systems, coupled with IrCl(COD)PPh₃ and chiral [SNNS]-type ligands, were employed in the asymmetric transfer hydrogenation of aromatic ketones under mild reaction conditions. The corresponding optically active alcohols were obtained in high yield and good to excellent enantioselectivities (up to 96% ee). The chiral Ir(I) complexes with the ligands of [SNNS]-type were also prepared and characterized, which showed good enantioselectivity and high activity. The reactions can be performed in air and the catalytic experiments are greatly simplified.     

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.     

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 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.     

Novel chiral dendritic diphosphine ligands for Rh(I)-catalyzed asymmetric hydrogenation: remarkable structural effects on catalytic properties

[reaction: see text] A series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of pyrphos 2 with Fréchet-type polyether dendron 3. The relationship between the primary structure of the dendrimer and its catalytic properties was established in the Rh-catalyzed asymmetric hydrogenation of alpha-acetamido cinnamic acid 4. A remarkable structural effect on catalytic activity was observed.     

Ruthenium(II)-catalyzed transfer hydrogenation of aldehydes with new water-soluble monotosylated ethylenediamines as ligands

New water-soluble monotosylated ethylenediamines containing quaternary ammonium groups were conveniently synthesized from ethylenediamine. The ruthenium catalysts prepared in situ from ruthenium complex [RuCl₂(p-cymene)]₂ and water-soluble monotosylated ethylenediamine ligands were used in transfer hydrogenation of aldehydes, and excellent conversions and chemoselectivities were achieved with sodium formate as reductant in neat water.     

Palladium(0)-catalyzed Mizoroki-Heck reaction and Rh(I)-catalyzed asymmetric hydrogenation of polymer-supported dehydroalanine system

We have developed a practical route for the synthesis of peptides containing unnatural amino acids. Mizoroki-Heck reaction of polymer-supported dehydroalanine, followed by asymmetric hydrogenation was accomplished using Pd(0) and Rh(I)-DuPHOS catalysts, respectively, leading to 36 dipeptides containing phenylalanine derivatives with high stereocontrol.     

New amidophosphine-phosphinites (tLANOPs) as chiral ligands for asymmetric hydrogenation reactions

The new amidophosphine-phosphinite (AMPP) ligands 4a–g (called tLANOP ligands) derived from the chiral hydroxy amide (R)- or (S)-2-hydroxy-3,3,N-trimethylbutyramide have been prepared in 48–83% yield. The crystal structures of the square planar complexes [(SP-4-3)-Pd((R)-dmphea)((S)-4a)]BF₄ and [Rh((R)-4a)(COD)]BF₄ have allowed the absolute configurations of the ligands to be assigned. In both complexes the 7-membered chelating ring of 4a has virtually the same twist-boat conformation. With this class of ligands the rhodium catalyzed asymmetric hydrogenation of 4-oxoisophorone enol acetate gave (S)-phorenol acetate in up to 71% ee. The iridium catalyzed asymmetric hydrogenation of the cyclic iminium salts 16a and 16b afforded after work-up the corresponding cyclic secondary amine (S)-17 in up to 86% ee, when bulky groups were present on the phenyl substituents on the two phosphorus atoms.     

Carboranylphosphites as new ligands for Rh-catalyzed asymmetric hydrogenation

First representatives of chiral carborane-based phosphite ligands were synthesized. The enantiomeric excess in the Rh-catalyzed hydrogenation of dimethyl itaconate with the use of these ligands reaches 67% in CH₂Cl₂ and 62% in supercritical CO₂, the ee and conversion being strongly dependent on the hydrogen pressure. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 337–340, February, 2008.     

Novel atropisomeric aminophosphine ligands with a bridge across the 5,5′-position of biphenyl for Rh(I)-catalyzed asymmetric hydrogenation

A new type of atropisomeric bisaminophosphine ligands 2 with a bridge across the 5,5′-position of biphenyl has been developed. The axial chirality of this type of ligands can be retained by macro-ring strain produced from 5,5′-linkage of biphenyl even without 6,6′-substituents on biphenyls. The ligand (R)-2a showed high catalytic activities and enantioselectivities (up to 95.3% ee and quantitative yields) for Rh(I)-catalyzed asymmetric hydrogenation of a variety of methyl (Z)-2-acetamido-3-arylacrylates.     

Iridium(I)-catalyzed regio- and enantioselective allylic amidation

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allyl carbonates with soft nitrogen nucleophiles under completely ‘salt-free’ conditions is described. A combination of [Ir(COD)Cl]₂, a chiral phosphoramidite ligand L^∗, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of N-Boc protected α- and β-amino acids as well as (−)-cytoxazone.     

Use of heterogenized dialdimine ligands in asymmetric transfer hydrogenation

Heterogenized dialdimine ligands complexed to iridium were tested in the asymmetric transfer hydrogenation of acetophenone. E.e.s of up to 70% were achieved but the recycling was unsatisfactory. When such ligands were used in asymmetric epoxidation of styrene, a modest e.e. of 15% was achieved.     

Cinchona alkaloid derived ligands in catalytic asymmetric transfer hydrogenation

A collection of chiral quinuclidine ligands, derived from the Cinchona alkaloids quinine and quinidine, has been evaluated in the catalytic asymmetric transfer hydrogenation of aromatic ketones. It was fond that [IrCl(COD)]2 complexes of the diamines QCI-Amine and QCD-Amine gave the most active catalysts, capable of reducing a range of aromatic ketones with excellent conversions and good enantioselectivities (up to 95% ee). These are the best selectivities reported for ligands based on the quinuclidine core in an asymmetric transformation, and advocate that these ligands, commercially available in both pseudo-enantiomeric forms, will find practical use in this and other catalytic processes.     

Evaluation of disaccharide-based ligands for Pd(0)-catalyzed asymmetric allylations

A series of phosphines based on disaccharides containing a d-glucosamine framework were prepared and tested for their abilities as ligands for the palladium(0)-catalyzed asymmetric allylic allylation of racemic 1,3-diphenyl-2-propenyl acetate with various nucleophiles. In contrast to previous results exploiting monosaccharides, the iminophosphines generally afforded higher enantiomeric excesses, up to 99%.     

N-Benzyl-norephedrine derivatives as new,efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones

Significant catalytic activities (up to 600 h⁻¹ at 20°C) and enantiomeric excesses ranging from 56 to 89% for the asymmetric transfer hydrogenation of β-ketoesters, methoxyacetone and 2-acetylpyridine to the corresponding alcohols are achieved in the presence of catalytic combinations of [RuCl₂(η⁶-arene)]₂ and N-substituted derivatives of (1S,2R)-norephedrine such as N-benzyl-norephedrine and N-(4-biphenyl)methyl-norephedrine.     

(-)-Menthol as a source of new N,N-diamine ligands for asymmetric transfer hydrogenation

The synthesis of new chiral N-monotosylated-1,2-diamines based on the (-)-menthol skeleton is presented. The elimination of HCl from neomenthyl chloride obtained from an Appel reaction led to p-menth-3-ene in excellent yield. Further functionalization of the double bond in p-menth-3-ene with chloramine-T gave the corresponding N-tosylaziridines, which upon reaction with sodium azide and subsequent reduction of the azide functional group, formed the 1,2-diamine system. The synthesized chiral ligands proved effective in the asymmetric transfer hydrogenation of aromatic ketones and an endocyclic imine.