Chiral Ferrocene Derivatives Research Articles

Ortho-lithiation of free ferrocenyl alcohols: a new method for the synthesis of planar chiral ferrocene derivatives

An ortho-metalation method for free ferrocenyl alcohols has been developed, which allows preparation of planar chiral ferrocene derivatives with high yields and diastereoselectivities.

Synthesis, Coordination and Catalytic Utility of Novel Phosphanyl–ferrocenecarboxylic Ligands Combining Planar and Central Chirality

AbstractThe chiral ferrocene derivative (R,Rp)‐2‐[1‐(diphenylphosphanyl)ethyl]ferrocenecarboxylic acid (1) is prepared together with selected derivatives resulting from modification at the phosphane moiety [P‐oxide (5) and P‐sulfide (4)] and the carboxyl group {amides bearing benzyl (6) and (R)‐ or (S)‐1‐phenylethyl substituents [(R)‐7 and (S)‐7] at the amide nitrogen atom}. Acid 1 and amide 6 are studied as ligands in rhodium and palladium complexes. Bridge cleavage of the dimer [{Rh(μ‐Cl)Cl(η5‐C5Me5)}2] with 1 gives [RhCl2(η5‐C5Me5)(1‐κP)] (9) containing P‐monodentate 1, which undergoes smooth conversion to the (phosphanylalkyl)ferrocenecarboxylato complex [RhCl(η5‐C5Me5){Fe(η5‐C5H5)(η5‐C5H3‐1‐CH(Me)PPh2‐2‐COO‐κ2O,P}] (10) upon treatment with silica gel or alumina. Yet another O,P‐chelate complex,[Rh{Fe(η5‐C5H5)(η5‐C5H3‐1‐CH(Me)PPh2‐2‐COO‐κ2O,P}(CO)(PCy3)] (11; Cy = cyclohexyl) is obtained directly by an acid‐base reaction between the acetylacetonato complex [Rh(acac)(CO)(PCy3)] and 1. Amide 6 reacts with [{Pd(μ‐Cl)(η3‐C3H5)}2] to give the expected phosphane complex [PdCl(η3‐C3H5)(6‐κP)] (12), while the replacement of the cyclooctadiene (cod) ligand in [PdCl(Me)(cod)] affords the chelate complex [PdCl(Me)(6‐κ2O,P)] (13). All compounds are characterised by spectroscopic methods and the solid‐state structures of 5, 9, 11, 13, (R,Sp)‐2‐[1‐(diphenylphosphoryl)ethyl]‐1‐[N‐(R)‐(1‐phenylethyl)carbamoyl]ferrocene [(R)‐8; phosphane oxide from (R)‐7], and the synthetic precursors (R,Sp)‐1‐bromo‐2‐[1‐(diphenylphosphanyl)ethyl]ferrocene (2) and (R,Sp)‐1‐bromo‐2‐[1‐(diphenylthiophosphoryl)ethyl]ferrocene (3) determined by single‐crystal X‐ray diffraction. The catalytic properties of 1 and the amides are probed in enanatioselective rhodium‐catalysed hydrogenation and palladium‐catalysed asymmetric allylic alkylation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Sulfur‐Containing Chiral Ferrocene Derivatives: Synthesis and Applications

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Synthesis and Structure of Planar Chiral, Bifunctional Aminoboronic Acid Ferrocene Derivatives

N,N‘-Diisopropylferrocenecarboxamide is utilized for an asymmetric, directed metalation approach to several planar chiral bifunctional ferrocene derivatives. Directed metalation using n-butyllithium-(−)-sparteine on N,N‘-diisopropylferrocenecarboxamide can be achieved to give high yields of the corresponding boronic acid; however, it was found that a sequence involving asymmetric directed metalation−bromination, followed by lithium−halogen exchange, was more convenient to access the same derivatives since this allowed straightforward determination of the enantiomeric excess. (pR)-2-[(N,N-Diisopropylamino)methyl]ferrocenylboronic acid and derivatives thereof could be readily accessed with high enantiomeric excess, followed by amide reduction.

Sulfur-Containing Chiral Ferrocene Derivatives: Synthesis and Applications

This account describes the different synthetic approaches used for the preparation of sulfur-containing chiral ferrocenes in which a CFc-S bond is present and the strategies for introducing planar and central chirality. The advantages of using these compounds as ligands for soft metals like palladium and copper are highlighted for several catalytic reactions, including the palladium-catalyzed enantioselective allylic alkylation, epoxidation, and aza-Diels-­Alder reactions.

Lipase/Ruthenium‐Catalyzed Dynamic Kinetic Resolution of β‐Hydroxyalkylferrocene Derivatives.

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Lipase/Ruthenium-Catalyzed Dynamic Kinetic Resolution of β-Hydroxyalkylferrocene Derivatives

National Research Laboratory of Chirotechnology, Department of Chemistry, Division of Molecular and Life Sciences,Pohang University of Science and Technology, Kyungbuk 790-784, KoreaReceived March 11, 2004An efficient dynamic kinetic resolution of racemic β-hydroxyalkylferrocene and 1,1'-bis(β-hydroxyalkyl)-ferrocene derivatives was achieved using lipase/ruthenium-catalyzed transesterification in the presence of anacyl donor. The racemic β-hydroxyalkylferrocene derivatives were successfully transformed to thecorresponding chiral acetates of high optical purities in high yields.Key Words : Dynamic kinetic resolution (DKR), Enzyme/metal bicatalysis, Lipase, β-HydroxyalkylferroceneIntroductionThe chiral ferrocene derivatives have been widely used aschiral ligands in asymmetric synthesis,

Optically Active Phospholanes as Substituents on Ferrocene and Chromium‐Arene Complexes

AbstractAn improved synthesis of (R,R)‐ and (S,S)‐hexane‐2,5‐diol is presented. The (S,S)‐derivative was converted into a cyclic sulfate, which on treatment with NaPH2 in liquid ammonia ultimately gave the secondary (R,R)‐2,5‐dimethylphospholane. This phospholane can be introduced into the side chain of chiral tricarbonylchromium and ferrocene derivatives to give new bidentate ligands of the Josiphos and Daniphos type. Both the ferrocene‐ and tricarbonylchromium‐based diphosphanes have been characterized by X‐ray diffraction analysis. A discussion of their structural features is included. The new ligands were successfully applied to the enantioselective hydrogenation of itaconic acid esters. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Synthesis of Novel Planar Chiral Ferrocene and Cyclopentadienyl Manganese Tricarbonyl Derivatives and Their Use as Chiral Ligands in the Palladium‐Catalyzed Asymmetric Allylic Alkylation.

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Synthesis of novel planar chiral ferrocene and cyclopentadienyl manganese tricarbonyl derivatives and their use as chiral ligands in the palladium-catalyzed asymmetric allylic alkylation

We have shown that cymantrene derivatives are better P,N-chelate ligands for palladium-catalyzed allylic alkylation than ferrocenes, which have a similar pentagonal ligand structure to cymantrene derivatives. In particular, the PPh 3-substituted cymantrene gave a higher enantioselectivity (>98%).

Chiral ferrocene cyanohydrin derivatives—access to novel intermolecularly linked and intramolecularly bridged ferrocene derivatives

By reduction of the cyano group in ( R)-(cyanohydroxymethyl)ferrocene and ( R, R)-1,1′-bis(cyanohydroxymethyl)ferrocene, amines were obtained giving access to several new diamine and diamide bridged chiral ferrocene derivatives. As a representative for an intramolecularly bridged ferrocene compound bearing two chiral centres ( R, R)- 8 was obtained with excellent optical purity.

Novel access to chiral 1,1′-disubstituted ferrocene derivatives via double stereoselective cyanohydrin synthesis exploiting the hydroxynitrile lyase from Hevea brasiliensis

A novel route to chiral ferrocene derivatives involving the application of hydroxynitrile lyase from Hevea brasiliensis has been developed. The method allows the conversion of formylferrocene 1 and 1,1′-diformylferrocene 2 into their corresponding chiral cyanohydrins. ( R)-(Cyanohydroxymethyl)ferrocene 3 and ( R, R)-1,1′-bis(cyanohydroxymethyl)ferrocene 4 were obtained in high yield and stereochemical purity using this method. The full structural characterisation of the latter including the determination of diastereomeric purity and the assignment of the absolute configuration is disclosed.

Separation of planar chiral ferrocene derivatives on β-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization

A series of β-cyclodextrin (β-CD) based chiral stationary phases (CSPs) were synthesized by ring-opening metathesis graft polymerization of various norborn-2-ene (NBE) substituted CDs. Chiral selectors based on endo/ exo-6- O-(norborn-2-ene-5-ylmethoxymethylsilyl)-β-CD, tris( endo/ exo-6- O-norborn-2-ene-5-ylmethoxymethylsilyl)-β-CD, tetrakis( endo/ exo-6- O-norborn-2-ene-5-ylmethoxymethylsilyl)-β-CD, hexakis( endo/ exo-6- O-norborn-2-ene-5-ylmethoxymethylsilyl)-β-CD and tetrakis( endo-6- O-norborn-2-ene-5-carboxyl)-β-CD were grafted onto Nucleosil 300-5 using well-established grafting procedures. CSPs were investigated for their separation capabilities for a series of the planar chiral ferrocene derivatives, rac-ferroceno[2,3 a]inden-1-one ( 1a, 1b), rac-6-(3-hydroxy-3-methylbut-1-yn-1-yl)ferroceno[2,3 a]inden-1-one ( 2a, 2b), rac-ferrocene[2,3 a]indene ( 3a, 3b), rac-endo 1-methoxy-1-allylferroceno[2,3 a]indene ( 4a, 4b) and rac-1,4-dihydroxybutylferrocene ( 5a, 5b). Compounds 1a, 1b and 2a, 2b bearing a carbonyl group were successfully separated on these CSPs, while compounds 3– 5 do not undergo enantioselective interaction under the conditions applied. General aspects of separation as well as mechanistic implementations are discussed.

Behavior of an Optically Active Ferrocene Chiral Shell Located within Phosphorus-Containing Dendrimers

Three families of phosphorus-containing dendrimers having chiral ferrocenic subunits precisely placed at one individual shell within their skeleton are synthesized. The influence of the progressive “burying” of the chiral ferrocene derivatives upon their electrochemical and chiroptical properties is reported. It is shown that both properties depend mainly on the chemical environment of the chiral organometallic centers. However, they differ in the sensitivity to the “burying”; the chiroptical properties do not appear to be sensitive to where the chiral units are positioned within the dendrimer, whereas the electrochemical properties are.

β-Ferrocenyl-β-amino alcohols: a new class of central chiral ferrocene derivatives

An efficient procedure for the enantioselective synthesis of β-ferrocenyl-β-amino alcohols, a new class of central chiral ferrocene derivatives suitable for the elaboration of auxiliaries and ligands for asymmetric synthesis, is described. Key steps of the method are the catalytic asymmetric dihydroxylation of 1-ferrocenyl alkenes and the regio- and stereoselective azide substitution of the hydroxyl group adjacent to the ferrocene moiety. The stereochemistry of the substitution step has been established by X-ray diffraction analysis of a cyclic derivative. The first catalytic enantioselective synthesis of a β-ferrocenyl-β-amino acid derivative is also disclosed.

Chirality sensing of saccharides using a boronic acid-appended chiral ferrocene derivative

A diboronic acid-appended chiral ferrocene derivative ( R )-9 was designed and synthesized. This chiral ferrocene scaffold was obtained by resolution of the diastereomer with a monosaccharide derivative. One can therefore expect that ( R )-9 would show d/ l selectivity for specific monosaccharides. The complex formation of ( R )-9 with various saccharides using the two boronic acid functions was conveniently monitored by a change in the circular dichroism (CD) spectra. The CD spectral change (Δ[ θ]) induced by added monosaccharides was chiroselective: in particular, d/ l-alloses and d/ l-galactoses induced the 8.0- and 7.0-fold difference in the magnitude of the CD spectral change. The association constants for d- and l-saccharides ( K D and K L, respectively) were determined: among them, ( R )-9 showed a significant discrimination ability for mannose ( K L/ K D=2.6) and arabinose ( K L/ K D=1/2.4). The origin of d/ l selectivity was discussed on the basis of computational studies on ( R )-9·saccharide complexes.

Chiral ferrocene derivatives containing a 2,2′-bridged binaphthyl moiety

Ten novel chiral ferrocene derivatives including some of interest as auxiliaries in asymmetric catalysis such as aminophosphines 2a– 2c and aminoalcohols 20 and 21 were selectively prepared in yields of 56–82% either from the corresponding bromoamines 12a, b and 18, respectively, via metal–halogen exchange or from ferrocenylamine 6 via ortho-lithiation. All of them contained the C 2-symmetrical 3,5-dihydro-4 H-dinaphth[2,1-c:1′,2′-e]azepine subunit as the chirality inducing fragment. Relative configurations were determined by crystal structure analyses of 2a and 2b.

ChemInform Abstract: Asymmetric Dihydroxylation Reactions Leading to Novel Chiral Ferrocene Derivatives.

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Asymmetric dihydroxylation reactions leading to novel chiral ferrocene derivatives

Several ferrocenyl alkenes were used as starting materials for asymmetric dihydroxylation reactions. Although they turned out to be unreactive employing Sharpless' standard conditions, by systematic variation of the reaction conditions the desired novel ferrocenyl diols could be obtained in good yields and in enantiomeric excesses up to >99%.

Ferrocene Derivatives Find Use As Chiral Catalysts

In the past few years, there has been a flurry of activity in the design and synthesis of chiral ferrocene derivatives. Aside from their intrinsic interest as a focus of basic research, these ferro...