Disubstituted Ferrocene Research Articles

1,1′-Disubstituted Ferrocenes as Molecular Hinges in Mono- and Bivalent Dopamine Receptor Ligands

On the basis of previous work on dopaminergic partial agonists of type 1 and 2, disubstituted ferrocenes are presented as valuable arene bioisosteres. Because substituents at the distal cyclopentadienyl ring are able to adjust the relative disposition that is required for ligand binding, disubstituted ferrocenes can act as molecular hinges. Taking advantage of click chemistry, the regioselective construction and functionalization of the target molecules is reported. Thus triazole derived appendages were used for the fine-tuning of biological activity and for the attachment of linker units generating bivalent GPCR ligands. Receptor binding was evaluated by radioligand displacement experiments, revealing superaffinity with sub- to single-digit nanomolar K(i) values for particular test compounds. As a neutral antagonist at the dopamine receptors D3 and D4 and a potent partial agonist at the D2 subtype (intrinsic activity = 57%, EC(50) = 2.5 nM), the bifunctional ferrocene 10b revealed a novel and unique activity profile.

Synthesis of Chiral 2‐Phospha[3]ferrocenophanes and their Behaviour as Organocatalysts in [3+2] Cyclization Reactions

AbstractPlanar chiral 2‐phospha[3]ferrocenophanes have been prepared via a stereoselective three‐step synthesis. The key step is the lithiation of the 1,1′‐disubstituted ferrocene 11 bearing (S)‐2‐(methoxymethyl)pyrrolidines as the chiral ortho‐directing groups. The diastereoselectivity of these reactions has been mastered by an appropriate choice of the metallating agent, so as to afford a suitable access to C2‐symmetrical, tetrasubstituted ferrocenes. These compounds have been converted into the enantiomerically pure 2‐phospha[3]‐ferrocenophanes 16, via the corresponding acetates and their reactions with primary phosphines. Phosphines 16 have been used as nucleophilic catalysts in model cyclization reactions. Unlike 2‐phospha[3]‐ferrocenophanes with stereogenic α‐carbons, the planar chiral derivatives 16 proved to be suitable catalysts for these processes. Thus, for instance, phosphine 16c successfully promotes the enantioselective [3+2] annulations of allenes and enones into functionalized cyclopentenes (ees up to 96%). Among others, spirocyclic derivatives have been obtained in good yields and ees in the range 77–85%. The robustness of this catalyst has been demonstrated by recycling experiments.

Novel redox active bifunctional crosslinkers from unsymmetrical 1,1′-disubstituted ferrocenes

The synthesis and electrochemistry of novel redox active bifunctional crosslinkers bearing pendant amine and maleimide groups from unsymmetrical 1,1′-disubstituted ferrocene precursors are reported.

Synthesis, Characterization and Reactivity of Dinuclear and Trinuclear Aluminum‐Bridged Ferrocenophanes

AbstractFerrocene derivatives bearing substituents with aluminum in the 1,1′‐positions, in the absence of donor ligands, possess rather unusual structural features. Starting from various dipyridine adducts of such 1,1′‐disubstituted ferrocene derivatives, it proved possible to trap the pyridine as the adducts R3Al(py) and monitor the formation of dinuclear and trinuclear aluminum‐bridged ferrocenophanes in solution by NMR spectroscopy. For the first time, the dynamic behaviour of such complexes was studied and a complete set of NMR spectroscopic data has been reported. The dinuclear complex [Fe(η5‐C5H4)2]2Al3Et5 was characterized by X‐ray structural analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis and physical properties of ferrocene derivatives. XXI. Crystal structure of a liquid crystalline ferrocene derivative, 1,1'-bis[3-[4-(4-methoxyphenoxycarbonyl)phenoxy]propyloxycarbonyl]ferrocene

The crystal structure of the title 1,1′-disubstituted ferrocene derivative was determined by X-ray diffraction using a single crystal. This compound exhibits a nematic phase only. The X-ray structure analysis revealed that the two substituents lie in the same direction (`U' shape) and the flexible spacer adopts agaucheconformation. These conformations are strongly related to the formation of a rod-like shape, which favors liquid crystalline behavior. In the crystal structure, C—H...π, π–π and T-stacking interactions were observed. It is considered that these interactions play a major role in stabilizing the molecular packing arrangement and the mesomorphism.

Structure of heteroannularly disubstituted ferrocene derivatives containing acetamido group

Methyl 1′-(acetamido)ferrocene-1-carboxylate ( 2), 1′-acetamidoferrocene-1-carboxazide ( 4) and methyl 1′-(1-acetamidoethyl)ferrocene-1-carboxylate ( 6) have been prepared and fully characterized. X-ray single crystal analysis showed that acetamido group in 2 and 4, methoxycarbonyl group in 2 and 6 and azidocarbonyl group in 4 are coplanar with adjacent cyclopentadienyl rings. In compound 6, acetamido group is perpendicular with respect to the plane of the cyclopentadienyl ring. Ferrocene cyclopentadienyl rings in 2 and 6 adopt an eclipsed conformation, while in 4 they deviate only slightly from this conformation. The molecules of 2 and 6 are self-assembled by one N H⋯O intermolecular hydrogen bond into infinite chains, while N H⋯O hydrogen bond in derivative 4 forms centrosymmetric dimer. 1H NMR and IR spectra measured in diluted solutions (nonpolar solvents) showed that acetamido-ester 2 and acetamido-azide 4 existed in a free forms 2A/ 4A, while at higher concentration they have tendency to form intermolecular hydrogen bonds. Solutions of conjugate 6 contained a mixture of conformers stabilized by intramolecular-hydrogen-bond 6B and open form 6A.

Preparation of Di-, Tri-, and Tetra-Substituted Functionalized Ferrocenes via Magnesium Organometallics

Ferrocenyl carboxylic acid derivatives were metalated with TMPMgCl·LiCl, leading after reaction with electrophiles to 1,2-disubstituted ferrocenes. Further metalation of these disubstituted ferrocenes with TMPMgCl·LiCl afforded trisubstituted ferrocenes. A 1,2,3,4-tetrasubstituted ferrocene derivative could also be prepared in this way.

New Molecular Wires with Two Ferrocene Hinges

Conventional molecular wires of the oligophenyleneethynylene (OPE) type are two-dimensional rigid molecules of fixed length. Possible problems concerning π,π stacking and device geometry associated therewith might be overcome by replacement of some of the 1,4-phenylene moieties by 1,1′-disubstituted ferrocene units. These make the wire three-dimensional thereby reducing the likelihood of intermolecular π,π interactions and serve in addition as hinges as a result of the almost free rotation around the Cp-Fe-Cp axis. This feature provides a limited conformational flexibility with the possibility of a length adjustment comparable to a foldable ruler. Here the syntheses and some physical properties of molecular wires containing two ferrocene hinges are described. In a number of cases the Sonogashira coupling reactions used for the coupling of the respective building blocks proceed much faster under microwave irradiation as compared to conventional heating.

Synthesis and Physical Properties of Ferrocene Derivatives (XX): Crystal Structure of a Liquid-Crystalline Ferrocene Derivative, 1,1′-bis [9-[4-(4-methoxyphenoxycarbonyl)phenoxy] nonyloxycarbonyl]Ferrocene

Single-crystal X-ray structure analysis has been performed for symmetrical 1,1′-disubstituted ferrocene derivative. This compound exhibits liquid crystallinity as a function of temperature with nematic and smectic liquid-crystalline phases. The X-ray structure analysis revealed that two substituents existed in the same directions, and as such induced the cis conformation (“U” shape) of the molecule. The molecules in the unit cell are arranged in a bookshelf manner. Within each layer, CH-π intermolecular interaction was observed at the substituents between neighboring molecules. It is considered that this interaction plays a predominant role in stabilizing the crystal packing arrangement and the mesomorphism.

Synthesis, structural characterization and electrochemical study of 1,1′-ferrocenylene labeled amino acids

Unsymmetrical 1,1′-disubstituted ferrocenes bearing an amino acid moiety and a conjugated electron density controlling substituent were synthesized conveniently starting from 1,1′-ferrocenedicarbaldehyde. The novel ferrocene amino acid derivatives were completely characterized from their MS, 1H NMR and 13C NMR spectra. Their electrochemical behavior was studied by cyclic voltammetry. Their formal redox potentials E f were slightly influenced by the nature of the amino acid and mainly by the kind of the ethenyl substituent. Furthermore all the ( Z)-isomers exhibited a slight anodic shift compared with the corresponding ( E)-isomers.

Substitution and ring-opening reactions of an azasubstituted [5]ferrocenophane: preparation of 1,1’-unsymmetrically disubstituted ferrocenes

New synthetic routes to 1,1'-unsymmetrically disubstituted ferrocene ligands bearing a quinoline ring directly linked to the ferrocene unit, along with the synthesis of a new structural motif based on an azasubstituted (5)ferrocenophane which incorporates a dihydroquinoline subunit, are presented.

Synthesis and characterization of porphyrin–ferrocene–fullerene triads

Novel porphyrin–fullerene systems linked by ferrocene and related model compounds were successfully synthesized and characterized. Conformationally flexible 1,1′-disubstituted ferrocene functioned as effective modulator of the conformation between porphyrin and fullerene, as 1H NMR spectra indicated, the porphyrin and C 60 moieties in the triads showed gauche type conformation. The electrochemical and photophysical studies showed that there were considerable interactions between porphyrin and fullerene in the ground state due to intramolecular π-stacking of the these two chromophores, assisted by the ferrocence linker. Fluorescence lifetime measurements indicated there might be two different quenching processes occurring simultaneously (intersystem crossing and electron transfer).

Discovery of a Pseudo β Barrel: Synthesis and Formation by Tiling of Ferrocene Cyclopeptides

Self-assembly of 1,n′-disubstituted ferrocene cyclopeptides leads to the first model of β barrels, a ubiquitous structural motif in proteins. The β-barrel model has eight β strands arranged almost parallel to the axis of the channel with an internal pore diameter of 8 Å.

Syntheses and Physical Properties of Ferrocene Derivatives (XVII) Crystal Structure of a Liquid Crystalline Ferrocene Derivative, 1,1′-bis[5-[4-(4-methoxyphenoxycarbonyl)phenoxy] pentyloxycarbonyl]ferrocene

ABSTRACT The molecular and crystal structures of 1,1′-disubstituted ferrocene derivative, 1,1′-bis[5-[4-(4-methoxyphenoxycarbonyl)phenoxy]pentyloxycarbonyl]ferrocene (bMAF-5) were determined by X-ray diffraction method using a single crystal. This compound is a liquid crystalline one. As generally expected, the molecular feature is “S” shape in which the two substituents are present in the opposite directions. The ‒C5H10 − chain introduced into the molecule as a flexible spacer includes two gauche conformations. The gauche conformation plays an important role to make a rod-like shape, which is favorable to show liquid crystallinity.

A Novel Molecular Structure of a Ferrocene Derivative Containing Mesogenic Group, 1,1′-Bis[2-[4-(4-methoxyphenoxycarbonyl)phenoxy]ethoxycarbonyl]ferrocene

Abstract The molecular and crystal structures of 1,1′-disubstituted ferrocene derivative, 1,1′-bis[2-[4-(4-methoxyphenoxycarbonyl)phenoxy]ethoxycarbonyl]ferrocene (bMAF-2) were determined by X-ray diffraction method using the single crystals. The trans conformation (novel “Z” shape) in which the two substituents existed in the opposite directions was found out newly. The structure was different from the cis conformation (“U” shape) and the trans conformation (“S” shape) reported already. It may be one of the most important reasons why bMAF-2 (“Z” shape) shows no liquid crystallinity that the ratio of the width to length is rather large compared with those of other liquid crystalline homologues (“U” shape and “S” shape).

Novel structure of 1,1'-disubstituted ferrocene derivative

Novel structure of 1,1'-disubstituted ferrocene derivative

Group 11 complexes with unsymmetrical P,S and P,Se disubstituted ferrocene ligands

The reaction of the unsymmetrical ligands 1-diphenylphosphino-1'-(phenylsulfanyl)ferrocene and 1-diphenylphosphino-1'-(phenylselenyl)ferrocene, Fc(EPh)PPh2(E = S, Se), with several group 11 metal derivatives leads to the synthesis of complexes of the type [MX{Fc(EPh)PPh2}](M = Au, X = Cl, C6F5; M = Ag, X = OTf), (OTf = trifluoromethanesulfonate), [M{Fc(EPh)PPh2}2]X (M = Au, X = ClO4; M = Ag, X = OTf), [M(PPh3){Fc(EPh)PPh2}]OTf (M = Au, Ag), [Au2{Fc(SPh)PPh2}2](ClO4)2, [Au(C6F5)2{Fc(SePh)PPh2}]ClO4, [Au(C6F5)3{Fc(EPh)PPh2}], [Au2(C6F5)6{Fc(SePh)PPh2}] or [Cu{Fc(EPh)PPh2}2]PF6(E = S, Se). In these complexes coordination depends upon the metal centre; with gold it takes place predominantly to the phosphorus atom and with silver and copper to both phosphorus and chalcogen atoms. The treatment of some of the gold complexes with other metal centres affords heterometallic derivatives that in some cases are in equilibrium with the homometallic derivatives. Several compounds have been characterized by X-ray diffraction, four pairs of homologous compounds, yet not a single pair is isotypic. In many of them a three dimensional network is formed through secondary bonds such as hydrogen bonds, Au...Cl or Au...Se interactions. The complex [Ag(OTf){Fc(SePh)PPh2}] forms one-dimensional chains through trifluoromethanesulfonate bridging ligands.

Covalent layer-by-layer type modification of electrodes using ferrocene derivatives and crosslinkers

A series of mono-substituted ferrocenes (Fecp 2 R, R = CONHCH 2N(C 2H 4NH 2) 2 ( 4), R = CH 2NHCH 2N(C 2H 4NH 2) 2 ( 5)) and di-substituted ferrocenes (Fe(cp R) 2, R = COF ( 3)) have been prepared, with 4 and 5 representing new compounds. The ferrocenes were grown layer-by-layer on metal oxide electrodes and crosslinked. The underlying principle of synthesis is based on repetitive and fast amide forming reactions between trimesic acid chloride ( 2) or Fe(cp COF) 2 ( 3) and tris(2-aminoethyl)amine ( 6), or one of the amine-substituted ferrocenes 4 or 5 on a 3-aminopropyl triethoxysilane (APS) ( 1) modified ITO, FTO or ATO electrode. Linear growth of the films electroactivity with the number of cascade steps is observed for up to 12 cascade steps yielding 1.1 × 10 −8 ferrocene centers/cm 2 on a flat ITO electrode, whereas 3 cascade steps yield 2.2 × 10 −7 ferrocene centers/cm 2 on a mesoporeous ATO electrode. In case of the ATO electrode, the inner walls of the mesopores exhibiting a very large surface are completely modified in the procedure. Beside this large coulometry fast electron transfer kinetics, high stability and low optical density in both oxidation states is observed. The electrodes were checked for their potential use as optically transparent counter electrodes in electrochromic devices.

Crystal Structure of a Liquid Crystalline Ferrocene Derivative, 1,1′-bis[10-[4-(4-methoxyphenoxycarbonyl)phenoxy]decyloxycarbonyl]ferrocene

Abstract The molecular and crystal structures of 1,1′-disubstituted ferrocene derivative, 1,1′-bis[10-[4-(4-methoxyphenoxycarbonyl)phenoxy]decyloxycarbonyl]ferrocene (bMAF-10) were determined by X-ray diffraction method using the single crystals. The structural molecular feature was the cis conformation (“U” shape) in which the two substituents existed in the same directions, but not the trans conformation (“S” shape) expected in general.

Asymmetric catalysis with chiral ferrocene ligands.

Chiral ferrocene ligands have been widely used in asymmetric catalysis. The advantages of using ferrocene as a scaffold for chiral ligands are described, particularly those regarding planar chirality, rigid bulkiness, and ease of derivatization. The role of planar chirality in 1,2- and 1,1'-disubstituted ferrocene systems is discussed. By using a bulky ferrocene fragment, novel ferrocene ligands were designed, and high enantioselectivity and regioselectivity were achieved in the allylic substitution reaction of monosubstituted allyl substrates. Using the tunable electronic properties of a diphosphine-oxazoline ferrocenyl ligand, the regioselectivity of the intermolecular asymmetric Heck reaction was also examined.