The application of a series of (cyclopentadienone)iron tricarbonyl complexes to “borrowing hydrogen” reactions between amines and alcohols was completed in order to assess their catalytic activity. The electronic variation of the aromatic groups flanking the C═O of the cyclopentadienone influenced the efficiency of the reactions; however, in other cases, the Knölker catalyst 1, containing trimethylsilyl groups flanking the cyclopentadienone ketone, gave the best results. In some cases, the change of the ratio of amine to alcohol improves the conversion significantly. The application of iron catalysts to the synthesis of a range of amines, including unsaturated amines, was investigated.

A series of strained alkynes were prepared from 2,2′-dihydroxy-biaryls. Several were characterised by X-ray crystallography, revealing strained C(sp)–C(sp)–C(sp3) bond angles in the range of 163–167°. Their cycloadditions with azides proceed without a catalyst. Functionalised versions of these reagents have potential applications to materials synthesis and bioconjugations.

A series of complexes containing the iron-cyclopentadienone structure were prepared by cyclising bis-propargylic alcohols and their derivatives with iron pentacarbonyl. The resulting complexes were characterised and tested in the catalysis of ketone reduction and alcohol oxidation. The complexes are competent catalysts for ketone reduction and alcohol oxidations.

An iron-tetraphenylcyclopentadienone tricarbonyl complex is demonstrated to act as a precursor of a catalyst for the formation of C–N bonds through a “hydrogen-borrowing” reaction between amines and alcohols.

A series of Ru(II)/arene complexes containing N-alkylated derivatives of TsDPEN were prepared and tested in the asymmetric transfer hydrogenation (ATH) of ketones. The results demonstrated that a wide variety of functionality were tolerated on the basic amine of the TsDPEN ligand, without significantly disrupting the ability of the catalyst to catalyse hydrogen transfer reactions.

•Novel Ru(II)/TsDPEN/iodo complexes have been prepared and characterised.•The catalysts furnish products of high ee in asymmetric reduction reactions.•The iodo complexes are as efficient as the chlorides in transfer hydrogenation.Two new iodide-containing derivatives of the widely-adopted arene/Ru(II)/TsDPEN catalysts have been prepared and fully characterised, including through X-ray crystallography. They have been evaluated as catalysts for the asymmetric reduction of acetophenone under both transfer (ATH) and pressure hydrogenation (AH) conditions. The iodide-containing complexes are equally efficient in the ATH reaction, but less active in the AH reaction compared to the chloride derivatives.Two new Ru(II) complexes have been prepared and evaluated as catalysts for the asymmetric reduction of acetophenone under both transfer and pressure hydrogenation conditions. The complexes are iodide-containing derivatives of the widely-adopted arene/Ru(II)/TsDPEN catalysts commonly used in these transformations.

The asymmetric transfer hydrogenation (ATH) of ketones under aqueous conditions using tethered Ru(II)/η6-arene/diamine catalysts is described, as is the ATH of electron-rich substrates containing amine and methoxy groups on the aromatic rings. Although such substrates are traditionally challenging ones for ATH, the tethered catalysts work very efficiently. In the case of amino-substituted ketones, aqueous conditions give excellent results; however, for methoxy-substituted substrates, the more established formic acid/triethylamine system gives superior results.

The asymmetric transfer hydrogenation of a series of diynones has been achieved in high conversion and enantiomeric induction. When R1 is a phenyl group, a competing alkyne reduction takes place; however, when R1 is an alkyl group, this side-reaction is not observed. The application of the reduction to the total synthesis of the natural product (S)-panaxjapyne A in high enantiomeric excess is described.

A series of novel enantiopure Ru(II) complexes containing a chiral diamine and η6-arene connected by a tethering group have been prepared and were evaluated in the asymmetric reductions of a range of ketones. Changes to the level of steric hindrance and the addition of an electron-withdrawing functionality on the sulfonyl group have a significant effect on the reactivity and enantioselectivity of the catalysts.

An ‘arene exchange’ approach has been successfully applied for the first time to the synthesis of Ru(II)-based ‘tethered’ reduction catalysts directly from their ligands in one step. This provides an alternative method for the formation of known complexes, and a route to a series of novel complexes. The novel complexes are highly active in both asymmetric transfer and pressure hydrogenation of ketones.

The asymmetric transfer hydrogenation of a series of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and 2,2-dimethyl-6-(2-oxoaryl)-1,3-dioxin-4-ones was achieved in high enantiomeric excess using a Ru(II) catalyst. The aryl substrates were most compatible with the methodology and this process facilitated a total synthesis of enantiomerically pure (+)-yashabushitriol.

A series of enantiomerically pure tridentate ligands based on the 1,2-diphenylethane-1,2-diamine structure, containing additional pyridine groups, was prepared and tested in asymmetric transfer hydrogenation of ketones using Ru3(CO)12 as a metal source. Alcohols were formed in up to 93% ee in the best cases, and good results were obtained with ortho-haloarylketones.

The cycloaddition of a chiral ligand containing a terminal alkyne to a soluble polymer containing an azide provides a convenient means for the attachment of an asymmetric transfer hydrogenation catalyst to a soluble polymer support. Using these ligands in complexes with Ru(II), gave good results in terms of conversion and enantioselectivity (up to 95% ee) in ketone reduction reactions.N-[(R,R)-2-(Prop-2-ynyloxyethylamino)-1,2-diphenylethyl]-4-methyl benzenesulfonamideC26H28N2O3See = 100%[α]D35=+5.6 (c 0.22, CHCl3)Source of chirality: Enantiomerically pure diamine.Absolute configuration: (R,R)N-[(R,R)-2-(1-Phenoxymethyl-1H-1,2,3-triazol-4-yl)methoxy ethylamino)-1,2-diphenylethyl]-4-methylbenzenesulfonamideC35H39N5O4See = 100%[α]D32=+6.7 (c 0.115, CHCl3)Source of chirality: Enantiomerically pure diamine.Absolute configuration: (R,R)N-[(R,R)-2-(1-Benzyl-1H-1,2,3-triazol-4-yl)butylamino)-1,2-diphenylethyl]-4-methylbenzene-sulfonamideC34H37N5O2See = 100%[α]D30=+4.7 (c 0.315, CHCl3)Source of chirality: enantiomerically pure diamine.Absolute configuration: (R,R)N-[(R,R)-2-(Hex-5-ynylamino)-1,2-diphenylethyl]-4-methyl BenzenesulfonamideC27H30N2O2See = 100%[α]D24=-26.6 (c 0.38, CHCl3)Source of chirality: enantiomerically pure diamine.Absolute configuration: (R,R)

A systematic study of the asymmetric transfer hydrogenations of functionalized acetylenic ketones and diketones has been completed, together with a total synthesis of (S,S)-(−)-yashabushidiol B. In several cases, excellent enantioselectivities and yields were achieved.

The synthesis of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione 4 from N-benzylglutarimide was achieved in three steps. The asymmetric hydrogenation of 4 gave either the product of partial reduction (10) or full reduction (13), depending on the catalyst which was employed, in high ee in each case. Attempts at asymmetric transfer hydrogenation (ATH) of 4 resulted in formation of a racemic product.

A new type of Ru(II)/TsDPEN catalyst containing an ether-based linking tether has been prepared and shown to exhibit excellent activity in asymmetric transfer hydrogenation reactions of ketones. Related complexes containing a hydroxyl-terminated alkyl chain have also been prepared and tested as asymmetric catalysts. In some cases the activity of the new catalyst type complements that of the closely related alkyl-chain tethered complexes.

A review of recent developments in the use of iron catalysts for asymmetric transformations, including hydrogenations, transfer hydrogenation, hydrosilylation and oxidation reactions.

The preparation of a range of asymmetric iron and ruthenium-cyclone complexes, and their application to the asymmetric reduction of a ketone, are described. The enantioselectivity of ketone reduction is influenced by a single chiral centre in the catalyst, as well as by the planar chirality in the catalyst. This represents the first example of asymmetric ketone reduction using an iron cyclone catalyst.

Ru(II) complexes of TsDPEN containing two alkyl groups on the non-tosylated nitrogen atom are poor catalysts for asymmetric transfer hydrogenation of ketones and imines; this observation provides direct evidence for the importance of the N–H interaction in the transition state for ketone reduction.

A series of (cyclopendienone)iron tricarbonyl complexes were prepared using an intramolecular cyclization strategy. These were applied to the catalysis of the oxidation of alcohols to aldehydes and ketones. When paraformaldehyde was used as the hydrogen acceptor, formate esters were obtained as coproducts and, in several cases, the major products.

This tutorial review describes recent progress in the development of homogeneous catalytic methodology for the direct generation of hydrogen gas from formic acid and alcohols.

A series of kinetic and structural investigations on ruthenium-based catalysts for asymmetric transfer hydrogenation (ATH) of ketones are reported. A method is reported for monitoring the formation of ruthenium hydride species in real time using 1H NMR spectroscopy.

A new inhibitor, containing a linked proline-piperidine structure, for the enzyme prolyl oligopeptidase (POP) has been synthesised and demonstrated to bind covalently with the enzyme at the active site. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing five-membered N-containing heterocyclic rings.The synthesis of a new inhibitor of prolyl oligopeptidase, containing a piperidine ring, together with an X-ray structure of its complex with the enzyme, is described. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing five-membered N-containing heterocyclic rings.

A stable aminal formed stereoselectively from (R,R)-N-tosyl-1,2-diphenyl-1,2-ethylenediamine (TsDPEN) is capable of asymmetric organocatalysis of Diels–Alder and α-amination reactions of aldehydes.

The highly enantioselective addition of acetone to 2-nitrostyrene, using N-diphenylphosphinyl-trans-1,2-diphenylethane-1,2-diamine (PODPEN) as a catalyst, is described.

Arene/Ru(II) complexes of (R,R)-N-alkyl-TsDPEN ligands are effective in the asymmetric transfer hydrogenation of ketones and imines in formic acid/triethylamine solution. The complex derived from the N′-Bn derivative of TsDPEN reduces monocyclic imines in up to 60% ee, whilst the N′-Me derivative of TsDPEN forms a more active catalyst than the non-alkylated analogue and reduces ketones in up to 97% ee.N′-(3,5-Dimethylbenzyl)-N-tosyl-1,2-diphenylethane-1,2-diamineC30H32N2O2SEe = 100%[α]D35=-36.4 (c 0.48, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (R,R)N′-(2,4,6-Trimethylbenzyl)-N-tosyl-1,2-diphenylethane-1,2-diamineC31H34N2O2SEe = 100%[α]D23=-26.4 (c 0.36, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (R,R)N′-(2,4,6-Trimethylbenzyl)-N-tosyl-1,2-diphenylethane-1,2-diamineC30H32N2O4SEe = 100%[α]D23=-39.1 (c 0.42, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (R,R)N′-(4-Methylbenzyl)-N-tosyl-1,2-diphenylethane-1,2-diamineC20H30N2O2SEe = 100%[α]D32=-42.7 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (R,R)N′-(3-Methylbenzyl)-N-tosyl-1,2-diphenylethane-1,2-diamineC20H30N2O2SEe = 100%[α]D32=-35 (c 0.6, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (R,R)Complex 24C36H37ClN2O2SRuEe = 100%[α]D31=-200.9 (c 0.007, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)Complex 25C37H39ClN2O2SRuEe = 100%[α]D30=+116 (c 0.01, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)Complex 26C36H37ClN2O4SRuEe = 100%[α]D31=-211.8 (c 0.005, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)Complex 27C35H35ClN2O2SRuEe = 100%[α]D29=-266.6 (c 0.01, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)Complex 28C37H39ClN2O2SRuEe = 100%[α]D31=-276.5 (c 0.009, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)Complex 18C36H37ClN2O2SRuEe = 100%[α]D21=-208 (c 0.0036, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)Complex 15C36H37ClN2O2SRuEe = 100%[α]D25=-404 (c 0.0023, CHCl3)Source of chirality: enantiomerically pure (R,R)-TsDPENAbsolute configuration: (R,R)1-Ethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolineC13H19NO2Ee = 89%[α]D26=-50.3 (c 0.1, CH2Cl2)Source of chirality: asymmetric reduction of dihydroisoquinolineAbsolute configuration: (S)1-Benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolineC18H21NO2Ee = 89%[α]D30=-8.3 (c 0.1, acetone)Source of chirality: asymmetric reduction of dihydroisoquinolineAbsolute configuration: (S)2-Phenyl-piperidineC11H15NEe = 60%[α]D25=+14.7 (c 0.08, CH2Cl2)Source of chirality: asymmetric reduction of imineAbsolute configuration: (R)2-(4-Methoxyphenyl)-piperidineC12H17NOEe = 57%[α]D31=+11.7 (c 0.32, CH3OH)Source of chirality: asymmetric reduction of imineAbsolute configuration: (R)2-(4-Methylphenyl)-piperidineC12H17NEe = 61%[α]D31=+36.7 (c 0.4, CHCl3)Source of chirality: asymmetric reduction of imineAbsolute configuration: (R)2-(4-Trifluoromethylphenyl)-piperidineC12H14F3NEe = 50%[α]D33=+14.4 (c 0.17, CHCl3)Source of chirality: asymmetric reduction of imineAbsolute configuration: (R)

The first report of an asymmetric transfer hydrogenation, in formic acid/triethylamine, of quinolines is described. Using a Ru(II) catalyst containing a 4-carbon tether, products of up to 73% ee were formed, whilst a Rh(III)-tethered catalyst gave products of up to 94% ee.N-((1R,2R)-2-(4-(3,5-Dimethylcyclohexa-1,4-dienyl)butylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamideC33H40N2O2See = 100%[α]D35=-5.3 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (RR)-TsDPENAbsolute configuration: (1R,2R)2-Methyl-1,2,3,4-tetrahydroquinolineC10H13Nee = 46%[α]D27=+46.7 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)2-Ethyl-1,2,3,4-tetrahydroquinolineC11H15Nee = 41%[α]D28=+35.6 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)2-Propyl-1,2,3,4-tetrahydroquinolineC12H17Nee = 42%[α]D24=+54.1 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)2-Butyl-1,2,3,4-tetrahydroquinolineC13H19Nee = 41%[α]D26=+46.6 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)2-Phenyl-1,2,3,4-tetrahydroquinolineC15H15Nee = 73%[α]D27=-31.3 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (S)2-Phenethyl-1,2,3,4-tetrahydroquinolineC17H19Nee = 50%[α]D25=+45.5 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)2-(3,5-Dimethoxyphenethyl)-1,2,3,4-tetrahydroquinolineC19H23NO2ee = 67%[α]D24=+39.5 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)2-(2-(6-Bromobenzo[d][1,3]dioxol-5-yl)ethyl)-1,2,3,4-tetrahydroquinolineC18H18BrNO2ee = 47%[α]D25=+25.6 (c 0.5, CHCl3)Source of chirality: asymmetric reduction of quinolineAbsolute configuration: (R)

The decomposition of a HCO2H/Et3N azeotrope to a mixture of hydrogen and carbon dioxide may be catalyzed by a number of Ru(III) and Ru(II) complexes with high efficiency at ca. 120 °C. Evidence that suggests that the precatalyst may in each case be a common ruthenium dimer has been obtained through 1H NMR and X-ray crystallographic studies of the complexes formed in situ and of analysis of the gases generated in the reaction using FTIR and gas chromatography methods.

A series of catalysts have been prepared for use in the asymmetric transfer hydrogenation of ketones. The complexes were prepared using a [4 + 2] cycloaddition reaction at a key step in the reaction sequence. This provides a means for the synthesis of catalysts with modifications at specific sites.

We report an optimised synthetic approach to the chiral derivatising agent (5R)-methyl-1-(chloromethyl)-2-pyrrolidinone. In addition, the observation of an unwanted dimerisation product is turned to our advantage by providing a method for the synthesis of a new class of C2-symmetric chiral diphosphine.Ethyl-(2S)-5-oxopyrrolidineC7H11NO3Ee = 100%[α]D22 = −6.8 (c 0.03, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S)[(2S)-5-Oxopyrrolidin-2-yl]methyl-4-methylbenzenesulfonate 4C12H15NO4SEe = 100%[α]D22 = −6.5 (c 0.013, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S)(5R)-5-Methylpyrrolidin-2-one 5C5H9NOEe = 100%[α]D22 = +15.8 (c 0.023, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (5R)(5R)-Methyl-1-(chloromethyl)-2-pyrrolidinoneC6H10NOClEe = 100%[α]D22 = +106.9 (c 0.021, CHCl3)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (5R)(5R)-5-Methyl-1-{[(2R)-2-methyl-5-oxopyrrolidin-1-yl]methylpyrrolidin-2-oneC11H18N2O2Ee = 100%[α]D22 = +207.7 (c 0.48, CHCl3)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (5R,2R)l-(+)-1,1′-Methylenebis[5-oxo-2-pyrrolidinecarboxylic acid]C11H14N2O6Ee = 100%[α]D22 = +104.0(c 0.022, H2O)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)l-(+)-1,1′-Methylenebis[5-oxo-2-pyrrolidinecarboxylic acid ethyl ester]C15H22N2O6Ee = 100%[α]D22 = +52.7 (c 0.0204, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)l-(+)-1,1′-Methylenebis[5-hydroxymethyl-2-pyrrolidinone]C11H18N2O4Ee = 100%[α]D22 = +91.3 (c 0.0145, H2O)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)l-(+)-1,1′-Methylenebis[toluene-4-sulfonic acid (S)-5-oxo-pyrrolidin-2-ylmethyl ester]C25H30N2O4S2Ee = 100%[α]D22 = +52.6 (c 0.0204, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)Methylenebis[5-diphenylphosphino-2-pyrrolidinone]C35H36N2O2P2Ee = 100%[α]D22 = +83.6 (c 0.031, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)

A Rh/tetramethylcyclopentadienyl complex containing a tethered functionality has been demonstrated to give excellent results in the asymmetric transfer hydrogenation of ketones in both aqueous and formic acid/triethylamine media.

The incorporation of a trans-1,2-diaminocyclohexane in place of DPEN provides improvements in enantioselectivity to asymmetric ketone hydrogenation reactions using BrXuPHOS–Ru–diamine catalysts. Substrates containing halogenated aryl rings are particularly compatible with this catalyst, however, α-chlorinated ketones remain resistant to reduction under any conditions.(S)-(−)-1-PhenylethanolC8H10OEe 90%[α]D23=+48.6(c0.10CH2Cl2)Determined by chiral GC analysis(S)-(−)-1-(3′-Trifluoromethylphenyl)ethanolC9H9F3OEe 93%[α]D20=-24.0(c0.24,MeOH)Determined by chiral GC analysis(S)-(−)-1-(4′-Trifluoromethylphenyl)ethanolC9H9F3OEe 90%[α]D22=-22.3(c0.62,MeOH)Determined by chiral GC analysis(S)-(−)-1-(2′-Bromophenyl)ethanolC9H9BrOEe 97%[α]D26=-54.5(c0.2,CHCl3)Determined by chiral GC analysis(S)-(−)-1-(2′-Iodophenyl)ethanolC9H9IOEe 97%[α]D29=-41.3(c0.20,CHCl3)Determined by chiral GC analysis(S)-(−)-1-(4′-Fluorophenyl)ethanolC8H9FOEe 93%[α]D30=-29.3(c0.22,CH3OH)Determined by chiral GC analysis(S)-(−)-1-(4′-Chlorophenyl)ethanolC8H9ClOEe 90%[α]D29=-37.8(c0.30,ether)Determined by chiral GC analysis(S)-(−)-1-(3′-Chlorophenyl)ethanolC8H9ClOEe 90%[α]D31=-24.1(c0.56,CHCl3)Determined by chiral GC analysis(S)-(−)-1-(2′-Chlorophenyl)ethanolC8H9ClOEe 94%[α]D29=-32.9(c0.22,CHCl3)Determined by chiral GC analysis(S)-(−)-1-(2′-Methylphenyl)ethanolC9H12OEe 92%[α]D24=-75.0(c0.15,EtOH)Determined by chiral GC analysis(S)-(−)-1-(2,5-Dimethyl-3-thienyl)ethanolC8H12SOEe 92%[α]D28=-16.4(c0.30,CHCl3)Determined by chiral GC analysis

A one-pot sequence of amine deprotection, intramolecular CN bond formation and subsequent asymmetric reduction may be promoted by a ruthenium catalyst.

A series of investigations have been completed on the use of the bis(diazaphospholidine) ligand ESPHOS in asymmetric hydroformylation. This study serves to confirm the optimum conditions for the use of this ligand. Two further ligands, based on ferrocene and biphenylether backbones, are also reported, but both give inferior results in hydroformylation in comparison with ESPHOS itself. The results from the hydroformylation reactions, and other studies, suggest that the ferrocene and biarylether systems are acting as monodonor ligands, rather than bidentate.GraphicFerriESPHOSC32H36FeN4P2Ee = 100%[α]17D=−96.2 (c 1.0, chloroform)Source of chirality: glutamic acid of (S)-configurationDiPhenESPHOSC34H36FeN4OP2Ee = 100%[α]18D=−397.5 (c 1.0, chloroform)Source of chirality: glutamic acid of (S)-configuration

The synthesis and applications to transfer hydrogenation of three derivatives of the popular TsDPEN are described. The results clearly demonstrate the importance of both disubstitution and the anti arrangement of substituents on this ligand. An explanation for the significance of these results is forwarded.GraphicN-((S)-2-Amino-2-phenyl-ethyl)-4-methyl-benzenesulfonamideC15H18N2O2SEe=100%[α]D20=+85 (c 1.50, CHCl3)Source of chirality: phenylglycinol of R-configurationN-((R)-2-Amino-1-phenyl-ethyl)-4-methyl-benzenesulfonamideC15H18N2O2SEe=100%[α]D20=+85 (c 1.50, CHCl3)Source of chirality: phenylglycinol of R-configurationN-((1S,2R)-2-Hydroxy-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC21H21NO3SEe=100%[α]D19=−29.2 (c 0.55, acetone)Source of chirality: (1R,2S)-2-aminodiphenylethanol(1R,2S)-1,2-Diphenyl-2-(toluene-4-sulfonylamino)-ethyl esterC22H23NO5S2Ee=100%[α]D19=−34.5 (c 0.50, acetone)Source of chirality: (1R,2S)-2-aminodiphenylethanolN-((1S,2R)-2-Azido-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC21H20N4O2SEe=100%[α]D19=−62.8 (c 0.55, acetone)Source of chirality: (1R,2S)-2-aminodiphenylethanolN-((1S,2R)-2-Amino-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC21H22N2O2SEe=100%[α]D=+34.8 (c 0.65, CHCl3)Source of chirality: (1R,2S)-2-aminodiphenylethanol

A range of 1-aryl-2-tetranols, and 1-phenyl-2-indanol, have been generated in high yield and enantiomeric excess from the corresponding racemic ketones, via a dynamic kinetic resolution–transfer hydrogenation process, using Ru(II)-TsDPEN in formic acid/triethylamine (5:2). This provides a potential entry to an asymmetric total synthesis of benzazepines such as Sch 39166.Graphic(1R,2S)-1-Phenyl-2-hydroxy-1,2,3,4-tetrahydronaphthaleneC16H16O[α]D20=−91.75 (c 2.06, CHCl3)Source of chirality: enantioselective transfer hydrogenationAbsolute configuration: 1R,2S(1R,2S)-1-(p-Methoxyphenyl)-2-hydroxy-1,2,3,4-tetrahydronaphthaleneC17H18O2[α]D20=−96.1 (c 3.90, EtOH)Source of chirality: enantioselective transfer hydrogenationAbsolute configuration: 1R,2S(1R,2S)-1-(p-Chlorophenyl)-2-hydroxy-1,2,3,4-tetrahydronaphthaleneC16H15ClO[α]D20=−124.7 (c 1.65, EtOH)Source of chirality: enantioselective transfer hydrogenationAbsolute configuration: 1R,2S(1R,2S)-1-Phenyl-2-hydroxy-1,2,3,4-tetrahydronaphthalene p-toluenesulphonyl esterC23H22O3[α]D20=−80.4 (c 1.03, CHCl3)Source of chirality: enantioselective transfer hydrogenationAbsolute configuration: 1R,2S(1R,2S)-1-Phenylindan-2-olC15H14O[α]D20=−49.67 (c 0.91, CHCl3)Source of chirality: enantioselective transfer hydrogenationAbsolute configuration: 1R,2S

The reduction of a number of α-substituted acetophenones has been achieved using both ruthenium(II)- and rhodium(III)-based asymmetric transfer hydrogenation catalysts employing formic acid as the hydrogen donor.Graphic

The palladium-catalysed reaction of the tert-butyldimethylsilyl ether of a 3-(o-bromophenyl)allylic alcohol with a methyl ketone leads directly to a 1-vinyl-1H-isochromene via a tandem ketone arylation–allylic cyclisation reaction.

The use of electrospray ionisation mass spectrometry for the detection of the intermediate species involved in the ruthenium(II)/amino alcohol reduction of ketones to alcohols is described.

We have designed and prepared a catalyst for the asymmetric reduction of ketones which combines a phosphinamide and a boron-containing heterocyclic ring. The former group acts to direct and activated the borane, whilst the latter provides a well defined position for location of the ketone. The resulting reduction therefore takes place in a well-defined stereochemical environment. Enantiomeric excesses of up to 59%, in a predictable absolute sense, were achieved. Evidence that O- co-ordination of borane is important in the reduction mechanism is also presentedThe synthesis and use of a novel catalyst for the asymmetric reductions of ketones by borane is described. Enantiomeric excesses of up to 59%, in a predictable sense, have been obtained.

A series of strained alkynes were prepared from 2,2′-dihydroxy-biaryls. Several were characterised by X-ray crystallography, revealing strained C(sp)–C(sp)–C(sp3) bond angles in the range of 163–167°. Their cycloadditions with azides proceed without a catalyst. Functionalised versions of these reagents have potential applications to materials synthesis and bioconjugations.

The preparation of a range of asymmetric iron and ruthenium-cyclone complexes, and their application to the asymmetric reduction of a ketone, are described. The enantioselectivity of ketone reduction is influenced by a single chiral centre in the catalyst, as well as by the planar chirality in the catalyst. This represents the first example of asymmetric ketone reduction using an iron cyclone catalyst.

A series of catalysts have been prepared for use in the asymmetric transfer hydrogenation of ketones. The complexes were prepared using a [4 + 2] cycloaddition reaction at a key step in the reaction sequence. This provides a means for the synthesis of catalysts with modifications at specific sites.

Ru(II) complexes of TsDPEN containing two alkyl groups on the non-tosylated nitrogen atom are poor catalysts for asymmetric transfer hydrogenation of ketones and imines; this observation provides direct evidence for the importance of the N–H interaction in the transition state for ketone reduction.

This tutorial review describes recent progress in the development of homogeneous catalytic methodology for the direct generation of hydrogen gas from formic acid and alcohols.

A series of complexes containing the iron-cyclopentadienone structure were prepared by cyclising bis-propargylic alcohols and their derivatives with iron pentacarbonyl. The resulting complexes were characterised and tested in the catalysis of ketone reduction and alcohol oxidation. The complexes are competent catalysts for ketone reduction and alcohol oxidations.

A series of kinetic and structural investigations on ruthenium-based catalysts for asymmetric transfer hydrogenation (ATH) of ketones are reported. A method is reported for monitoring the formation of ruthenium hydride species in real time using 1H NMR spectroscopy.

A review of recent developments in the use of iron catalysts for asymmetric transformations, including hydrogenations, transfer hydrogenation, hydrosilylation and oxidation reactions.

A new type of Ru(II)/TsDPEN catalyst containing an ether-based linking tether has been prepared and shown to exhibit excellent activity in asymmetric transfer hydrogenation reactions of ketones. Related complexes containing a hydroxyl-terminated alkyl chain have also been prepared and tested as asymmetric catalysts. In some cases the activity of the new catalyst type complements that of the closely related alkyl-chain tethered complexes.

The synthesis of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione 4 from N-benzylglutarimide was achieved in three steps. The asymmetric hydrogenation of 4 gave either the product of partial reduction (10) or full reduction (13), depending on the catalyst which was employed, in high ee in each case. Attempts at asymmetric transfer hydrogenation (ATH) of 4 resulted in formation of a racemic product.