Chiral Diphosphine Ligands Research Articles

Asymmetric hydrogenation of ( E)-α,β-bis( N-acylamino)acrylates catalyzed by a rhodium complex with trans-chelating chiral diphosphine ligand

The asymmetric hydrogenation of ( E)-α,β-bis( N-acylamino)acrylates was promoted by a rhodium complex bearing a trans-chelating chiral diphosphine ligand ( R, R)-( S, S)-PrTRAP, providing the corresponding optically active (2 S,3 R)-2,3-bis( N-acylamino)carboxylates with 79–82% ee. The 2,3-bis( N-acylamino)carboxylates isolated were readily hydrolyzed under acid to afford (2 S,3 R)-2,3-diaminocarboxylic acids in 95% yield without epimerization.

A New Palladium(II)-Catalyzed Asymmetric Chlorohydrin Synthesis

The Pd(II)-catalyzed oxidation of ethene in aqueous solution (Wacker reaction) gives exclusively acetaldehyde at low [Cl-] (1.0 M). At high [Cl-] (>2.5 M) and high [CuCl2] (>3 M), formation of ethylene chlorohydrin occurs to an appreciable extent (Scheme 1).1,2 Previous studies in these laboratories have shown that substitution of chloride by pyridine in the coordination sphere of PdCl4 to give PdCl3(pyridine) resulted in the formation of chlorohydrin at [Cl-] as low as 0.2 M.3,4 At this low [Cl-], PdCl4 gives only acetaldehyde at any [CuCl2]. This finding opens up the possibility of an asymmetric chlorohydrin synthesis with R-olefins. Pd(II) catalysts containing chiral auxiliaries should produce optically active products. The logical starting point is the replacement of pyridine with a chiral amine L*. Scheme 2 outlines the general reaction scheme with monodentate chiral amines such as (CH3)2C*NH(CH3)Ph. As shown, the two positional isomers, 2 and 3, arise from the two possible modes of hydroxypalladation. The ratio 2/3 of about 4 for propene and 1-pentene is typical for a number of catalysts. As expected, the optical purity of 2 was low, with ee’s of 10-15%. Catalysts with chiral chelating diphosphines should give much higher optical purities. However, the monometallic Pd(II) complex containing a diphosphine ligand is a neutral species and thus insoluble in the reaction media. The solution to this problem involved two different approaches. One approach used sulfonated chiral ligands while the other involved bimetallic complexes with a bridging diphosphine ligand.6 The structures of the two catalytic systems are shown below. Synthesis of the tetrasulfonated ligand involved treatment of Tol-BINAP with H2SO4 containing 20% SO3 at room temperature for 24 h followed by neutralization with NaOH.7 Recrystallization from methanol provided pure samples. Reaction with K2PdCl4 or PdCl2(PhCN)2 provided the chiral catalyst. 31P NMR measurements confirmed that all the tolyl rings were sulfonated. In these catalysts X ) Cl. Treatment of a solution of [Pd(CH3CN)4]BF4 in CH3CN with 1,3,5-pentanetriones gave the bimetallic triketone complexes. Addition of the chiral diphosphine ligand provided the chiral bimetallic complex. After purification, the products were characterized by elemental analysis and 1H13C and 31P NMR. As initially prepared, X is the CH3CN ligand. However, in the actual reaction mixtures, CH3CN is almost certainly replaced by Cl-. Gas uptake measurements using gas burets monitored the progress of the reactions.8,9 Propene oxidation was monitored by propene consumption. With the other nongaseous olefins the gas was dioxygen. This is possible because the CuCl formed in the first oxidation step to form chlorohydrin readily reacts with dioxygen to give CuCl2. Thus, as with the Wacker reaction, the chlorohydrin synthesis is a net air oxidation.

Asymmetric aldol reaction of 2-cyanopropionates catalysed by trans-chelating chiral diphosphine ligand TRAP–rhodium(I) complex

trans-Chelating chiral diphosphine TRAP ligands bearing P-aromatic groups are effective for RhI-catalysed asymmetric aldol reaction of 2-cyanopropionates with an aldehyde to give the corresponding aldol adduct with up to 93% ee.

Asymmetric deuteration of N-acetyl-( Z)- α, β-dehydrotryptophan-( L)-phenylalanine methyl ester produced by ( L)-tryptophan 2′,3′-oxidase from Chromobacterium violaceum. A new route for stereospecific labelling of peptides

A novel approach to the synthesis of labelled ( 2H, 3H) peptides through the catalytic asymmetric reduction of Δ ZTrp containing peptides, using rhodium complexes with chiral diphosphine ligands as the catalysts, is described. Ac-Δ ZTrp-( L)-Phe-OMe is used as a model substrate to study this new route. The (Z)-α,β-dehydropeptide is produced by ( L)-tryptophan 2′,3′-oxidase from Chromobacterium violaceum in a single step reaction. Diastereomeric excesses up to 98 % have been obtained with ( R, R)-dipamp as ligand in the catalyst. Extremely high stereoselectivities for producing the ( L, L)- or ( D, L)-isomer could be achieved using the appropriate chiral ligands. This method has good potential for stereospecific labelling (deuteration or tritiation) of peptides.

The asymmetric Heck reaction: recent developments and applications of new palladium diphenylphosphinopyrrolidine complexes

The development of the intermolecular and intramolecular asymmetric Heck reactions catalysed by palladium complexes of chiral diphosphine ligands, mainly (R)–BINAP, is reviewed. Recent developments using chiral phosphinamine ligands, including some preliminary results on the application of new diphenylphosphinopyrrolidine ligands to the intermolecular asymmetric Heck, are presented. These ligands show good regioselectivities but moderate enantioselectivities when compared to the phosphinooxazoline ligands. The latter class has extended the range of substrates to which the asymmetric Heck can be applied and exhibit better reactivities, regioselectivities and enantioselectivities when compared to (R)–BINAP. The exploitation of the intramolecular asymmetric Heck reaction in total synthesis is demonstrated through asymmetric approaches to a range of bioactive natural products. Some of the more recent mechanistic investigations of the Heck reaction are also discussed.

Novel C2-symmetric diphosphine ligand with only the planar chirality of ferrocene

The first C 2-symmetric diphosphine ligand possessing only the planar chirality of ferrocene was prepared from 1,1′-bis(diphenylphosphino)-2,2′-bis(oxazolinyl)ferrocene by the transformation of the oxazoline moieties in the molecule and with this new chiral ferrocene diphosphine ligand, up to 92% ee was obtained for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with 2,4-pentanedione.

Immobilized catalysts for enantioselective hydrogenation: The effect of site-isolation

Functionalized PPM (PPM: (2 S,4 S)-4-dihpenylphosphino-2-(diphenylphosphino-methyl) pyrrolidine), a chiral diphosphine ligand, was bound to silica gel with different loadings [mmol ligand/g support] and used as model to detect possible effects of site isolation in the enantioselective hydrogenation of methyl-acetamidecinnamate (MAC) with cationic and with neutral Rh-catalysts and of N-(2-methyl-6-ethylphen-1-yl) methoxymethylmethylketimin (MEI) with an Ir-catalyst. To investigate the influence of high local catalyst concentration in absence of a support, two new bis-PPM ligands with spacers of different length were prepared and tested. The results indicate that site isolation effects occur with two of the catalytic systems used: Whereas immobilized cationic Rh-catalysts are practically not affected, the neutral Rh-catalysts lose most of their activity with increasing catalyst loading. Probably, this is due to the formation of chloride-bridged Rh-dimers which is favored by high catalyst concentration as indicated by experiments with the bis-PPM-ligands. Immobilization has a spectacular effect with the Ir-system. It is known that Ir-complexes in presence of hydrogen can form stable hydrogen-bridged dimers that are catalytically inactive. The fact that the activity (and also productivity) of the immobilized catalysts increases with decreasing catalyst loading indicates, that the formation of these dimers can be prevented by immobilization.

Halogen Exchange in Platinum−Phosphine−Tin(II) Halide Systems. Characterization of the Novel PtI(SnCl3)[(2S,4S)-2,4-bis(diphenylphosphino)pentane] Complex

The investigation of the PtCl2(diphosphine) + SnI2 and PtI2(diphosphine) + SnCl2 systems of catalytic importance (where diphosphines are 2,3-bis(diphenylphosphino)butane and 2,4-bis(diphenylphosphino)pentane) by NMR in solution has been carried out. Novel PtI(SnCl3)(diphosphine) and PtI(SnCl2I)(diphosphine) complexes were formed as a consequence of the halide exchange reaction. The selective formation of PtI(SnCl3)[2,4-bis(diphenylphosphino)pentane] was observed in the reaction of PtCl2[2,4-bis(diphenylphosphino)pentane] and 0.5 SnCl2 and 0.5 SnI2. PtI(SnCl3)[2,4-bis(diphenylphosphino)pentane], the first platinum complex which contains a chiral chelating diphosphine and SnCl3 ligand, was structurally characterized by X-ray diffraction.

New Class of Chiral Diphosphine Ligands for Highly Efficient Transition Metal-Catalyzed Stereoselective Reactions: The Bis(diphenylphosphino) Five-membered Biheteroaryls.

The synthesis and application of three examples of a new class of chiral (C(2)) atropisomeric diphosphines characterized by two interconnected five-membered heteroaromatic rings, with hindered rotation around the interanular bond, are described. Optically pure (+)- and (-)-2,2'-bis(diphenylphosphino)-4,4',6,6'-tetramethyl-3,3'-bibenzo[b]thiophene (tetraMe-bitianp) (1a) and the parent unsubstituted system (+)- and (-)-bitianp (1b) were synthesized. They were found to be optically stable at 100 degrees C and were successfully employed as ligands in the Ru(II)-catalyzed hydrogenation of alpha- and beta-oxo esters to the corresponding alpha- and beta-hydroxy esters and in the hydrogenation of olefinic substrates. The optical and chemical yields were comparable with those reported for the same Ru(II)-binap-catalyzed reactions carried out under the same experimental conditions. The 2,2'-bis(diphenylphosphino)-3,3'-bibenzo[b]furan (1c), the oxygenated analogue of bitianp, was found to be configurationally unstable at room temperature. Complete structural X-ray elucidation of the Pd complexes of 1a-c is reported. The advantages of these biheteroaromatic ligands over the classical biaryl systems are discussed.

Catalytic asymmetric hydrogenation of dimethyl itaconate with trans-chelating chiral diphosphine ligands TRAP-rhodium complexes

Abstract Asymmetric hydrogenation of dimethyl itaconate catalyzed by the trans-chelating chiral diphosphine ( R , R )-( S , S )-EtTRAP-rhodium complex gave ( S )-dimethyl 2-methylsuccinate with 96% ee. Dimethyl 2-isopropylidenesuccinate, a tetrasubstituted olefin substrate, was also hydrogenated with ( R , R )-( S , S )-BuTRAP-rhodium complex in high enantioselectivity (78% ee), but with opposite enantioselection.

Asymmetric Michael reaction of an α-cyano Weinreb amide catalyzed by a rhodium complex with trans-chelating chiral diphosphine PhTRAP

Asymmetric Michael reaction of N-methoxy- N-methyl-2-cyanopropionamide with vinyl ketones or acrolein in the presence of 0.1–1 mol% of a rhodium catalyst prepared in situ from Rh(acac)(CO) 2 and a trans-chelating chiral diphosphine ligand ( S, S)-( R, R)-PhTRAP gave optically active Michael adducts with high enantiomeric excesses (89–94%) in high yields. The adducts with methyl vinyl ketone was transformed into an α-cyano aldehyde and ketones with an quarternary asymmetric carbon center through the reaction with LiAlH 4 or Grignard reagents.

Chemo and Enantioselective Butadiene-functionalized Dienes Cyclodimerization catalyzed by Nickel Complexes

Chiral aminophosphine-phosphinite and diphosphine ligands induce chirality during nickel catalyzed cyclodimerization of conjugated dienic esters with butadiene. The enantiomeric excesses of the cyclodimers are determined by chiral GLC and NMR methods. Graphic

Chemo and enantioselective butadiene-functionalized dienes cyclodimerization catalyzed by nickel complexes

Chiral aminophosphine-phosphinite and diphosphine ligands induce chirality during nickel catalyzed cyclodimerization of conjugated dienic esters with butadiene. The enantiomeric excesses of the cyclodimers are determined by chiral GLC and NMR methods.

(Diphenylphosphino)-biheteroaryls: the first example of a new class of chiral atropisomeric chelating diphosphine ligands for transition metal catalysed stereoselective reactions

Ruthenium(II) dichloride complexes with (+)- and (–)-2,2′-bis(diphenylphosphino)-4,4′,6,6′-tetramethyl-3,3′-bibenzo[b]thiophene (1a), new chiral atropisomeric heterocyclic ligands, reduce α- and β-oxoesters to α- and β-hydroxyesters with an enantiomeric purity comparable, if not higher, to that reported for binap under the same experimental conditions.

Catalytic asymmetric synthesis of peptides on polymer support

A novel approach to the synthesis of peptides through the catalytic asymmetric hydrogenation of dehydrotripeptides linked to the Wang resin, using rhodium complexes with chiral diphosphine ligands as the catalysts, is described.

Asymmetric Michael reaction of α-cyano carboxylates catalyzed by a rhodium complex with trans-chelating chiral diphosphine PhTRAP

Asymmetric Michael reaction of 2-cyanopropionates with vinyl ketones or acrolein in the presence of 0.1–1 mol% of a rhodium catalyst prepared in situ from RhH(CO)(PPh 3) 3 and a trans-chelating chiral diphosphine ligand ( S,S)-( R,R)-PhTRAP in benzene at 3–5°C gave optically active Michael adducts with high enantiomeric excesses (83–93% ee) in high yields. The reaction of 2-cyanopropionate with methacrolein and crotonaldehyde proceeded somewhat slowly, giving diastereomer mixtures in moderate enantioselectivities but in low diastereoselectivities. The reaction of 2-cyanobutyrate and 2-cyano-3-methylbutyrate with acrolein gave corresponding Michael adducts with much lower enantiomeric excesses than that of 2-cyanopropionates. The Michael addition product from acrolein was converted into an optically active α-methyl-α-amino acid.

ChemInform Abstract: Synthesis and Properties of a New Chiral Diphosphine Ligand Bearing a Cyclodextrin‐Based Molecular Recognition Site and Its Palladium(II) Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantiomeric ligands of phosphorus made

Chemists at Harvard University have devised asymmetric syntheses of enantiomeric phosphine ligands, chiral at phosphorus, to make asymmetric reaction catalysts [ J. Am. Chem. Soc , 115, 11000 (1993)]. The Harvard achievement avoids resolutions of racemates, which result in 50Vc of the synthesized material being an unwanted enantiomer. The Harvard chemists note the importance of having suitable chiral phosphine or diphosphine ligands in development of transition-metal catalysts for enantioselective reactions, especially hydrogenation processes. The new method allows chemists to choose the absolute configuration of the product phosphine in advance, and also to decide which of two phosphine enantiomers to synthesize. Moreover, enantiomeric excesses are higher than 97%. And the method is so general that it makes available a wide variety of phosphine ligands, which in turn will lead to even further development of enantioselective catalysts. Organic chemistry professor Elias J. Corey and postdoctoral fellows Zh...

Synthesis and properties of a new chiral diphosphine ligand bearing a cyclodextrin-based molecular recognition site and its palladium(II) complex

A new chiral diphosphine tethered to heptakis(2,6-di-O-methyl)-β-cyclodextrin was synthesized and converted to a water soluble palladium(II) complex. Conductivity and dynamic light scattering measurements and UV-VIS spectra indicated that the palladium complex is aggregated in aqueous solution.

ChemInform Abstract: Catalytic Asymmetric Synthesis with Trans‐Chelating Chiral Diphosphine Ligand TRAP: Rhodium‐Catalyzed Asymmetric Michael Addition of α‐ Cyano Carboxylates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.