Chiral Ferrocenyl Research Articles

Synthesis, Crystal Structure of Chiral Ferrocenyl Amino Alcohols, and Its Use for Asymmetric Transfer Hydrogenation

Two chiral ferrocenyl amino alcohols (IIIa and IIIb) have been synthesized for the iridium catalyzed asymmetric transfer hydrogenation of aromatic ketones. The structures of two chiral ferrocenyl amino alcohols have been determined by single crystal X-ray diffraction (CIF files CCDC nos. 1056737 (IIIa) and 1056734 (IIIb)). The results show that the activity and enantioselectivity of the chiral iridium catalyst are very sensitive to the substrate structure. Ir(I)-catalyzed asymmetric transfer hydrogenation of acetophenone resulted in moderate to good yield and lower enantioselectivity; asymmetric transfer hydrogenation of proopiophenone and 2-benzoylpyridine resulted in lower yield and lower enantioselectivity; as for 4-benzoylpyridine, good results have been achieved.

Ir-catalyzed asymmetric hydrogenation of simple ketones with chiral ferrocenyl P,N,N-ligands

The Ir-catalyzed asymmetric hydrogenation of simple aromatic ketones with chiral ferrocenyl P,N,N-ligands has been developed. Under the optimized conditions, a wide range of ketones were hydrogenated to afford the corresponding chiral alcohols in good to excellent enantioselectivities (up to 98% ee).

Diastereoselective synthesis, structure and reactivity studies of ferrocenyloxazoline gold(i) and gold(ii) complexes

In the last few decades, gold complexes have demonstrated huge potential for soft Lewis acid catalysis. Despite the intensive research on Au complexes and planar chiral metallacycles, enantiopure ferrocenylgold complexes have - surprisingly - not been reported until the studies presented in this article. Herein, we report the asymmetric synthesis of planar chiral ferrocenyl Au(i) complexes. These dinuclear species form helically chiral ten-membered (NCCCAu)2 rings stabilized by aurophilic interactions. In supramolecular solid state structures, linear, zigzag or helical Au(i) wires with regular AuAu separations were observed. The dissolved dinuclear entities could be oxidized by Au(i) to unique ferrocenyl Au(ii) complexes featuring short Au(ii)-Au(ii) bonds, while the ferrocene core remained intact. However, our initial studies revealed the issue of configurational lability of the ferrocenyl Au(ii) complexes in terms of the element of planar chirality in the presence of the gold source, (Me2S)AuCl. This was successfully addressed by a systematic study implementing permanent σ-donor ortho-protecting groups such as methyl and trimethylsilyl, which impede an epimerization event. Oxidation of the dinuclear Au(i) complexes was also accomplished by oxidative addition reactions with halogenated solvents, preferably CHCl3. Additional reactivity studies revealed that dinuclear Au(ii) dihalide complexes are also formed with reactive alkylhalides such as iodomethane, benzylbromide and benzyliodide. Interestingly, the whole spectral range of colors (violet, blue, green, yellow, and red) is covered by the title complexes depending on the Au oxidation state and the anionic ligands in the Au(ii) complexes. This appears to be quite unusual for ferrocenes, which typically adopt orange to red colors in a non-oxidized state.

Chiral phosphinites as efficient ligands for enantioselective Ru(II), Rh(I) and Ir(III)-catalyzed transfer hydrogenation reactions

Metal-catalyzed enantioselective transfer reduction of ketones to enantiomerically enriched chiral alcohols has recently attracted attention. Therefore, a series of methyl alkyl or alkyl/aryl ketones have been reduced by using Ru(II), Rh(I) and Ir(III) catalysts based on C 2-symmetric chiral ferrocenyl phosphinite ligands. The corresponding optically active secondary alcohols were obtained in excellent conversions and moderate-to-good enantioselectivities. The best results were obtained with an iridium catalyst, giving up to 98% conversion and 80% ee.

Silver-catalyzed diastereo- and enantioselective Michael additions of 2-oxazoline- and 2-thiazoline-4-carboxylate to nitroalkenes

The silver/ThioClickFerrophos (a chiral ferrocenyl P,S-ligand)-catalyzed Michael additions of 2-oxazoline- and thiazoline-4-carboxylate to nitroalkenes were highly anti-selective and enantioselective and produced the corresponding adducts in high yields.

Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands

The Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands has been developed, providing the corresponding β-hydroxy esters in good to excellent enantioselectivities.

A new ferrocenyl bisphosphorus ligand for the asymmetric hydrogenation of α-methylene-γ-keto-carboxylic acids.

Upon incorporation of a noncovalent ion pair interaction, a new chiral ferrocenyl bisphosphorus ligand t-Bu-Wudaphos was developed. t-Bu-Wudaphos can be easily synthesized with very high diastereoselectivity as a highly air stable solid. The new ligand exhibited excellent reactivities and enantioselectivities in the asymmetric hydrogenation of α-methylene-γ-keto-carboxylic acids via an ion pair noncovalent interaction (up to >99% conversion, >99% ee).

Sterically Hindered Chiral Ferrocenyl P,N,N-Ligands for Highly Diastereo-/Enantioselective Ir-Catalyzed Hydrogenation of α-Alkyl-β-ketoesters via Dynamic Kinetic Resolution.

A new class of sterically hindered chiral ferrocenyl P,N,N-ligands have been prepared through a two-step transformation from (Sc,Rp)-PPFNH2, in which a new (R)-stereogenic center at the pyridinylmethyl position was generated in high diastereoselectivity. With these newly developed P,N,N-ligands, Ir-catalyzed asymmetric hydrogenation of various α-alkyl-substituted β-aryl-β-ketoesters via dynamic kinetic resolution has been realized in high diastereo- and enantioselectivities for the first time, which led to a variety of optically active anti-β-hydroxyesters in up to 99% ee. The study indicated that the additional stereocenter at the pyridinylmethyl position of these ligands is crucial to realize this hydrogenation.

Synthesis of MeO-PEG2000-supported chiral ferrocenyl oxazoline carbinol ligand and its application in asymmetric catalysis

A simple method for the synthesis of a MeO-PEG-supported chiral ferrocenyl oxazoline carbinol ligand has been developed. The chiral ligand was successfully applied to the catalytic asymmetric addition of diethylzinc to aryl aldehydes, affording secondary alcohols in high yields and with excellent enantioselectivities (up to 94% ee). The chiral ligand can be recovered and reused twice with no apparent loss of catalyst efficiency.

ChemInform Abstract: Chiral Ferrocenyl P,N‐Ligands for Palladium‐Catalyzed Asymmetric Formal [3 + 2] Cycloaddition of Propargylic Esters with β‐Ketoesters: Access to Functionalized Chiral 2,3‐Dihydrofurans.

A highly enantioselective palladium-catalyzed [3 + 2] cycloaddition of propargylic esters with β-ketoesters has been realized by employing a newly developed chiral ferrocene/benzimidazole-based P,N-ligand. This protocol features a good tolerance of functional groups in both propargylic esters and β-ketoesters, thereby delivering a variety of highly functionalized chiral 2,3-dihydrofurans bearing an exocyclic double bond at the 3-position in good yields and with high enantioselectivities (up to 98% ee).

ChemInform Abstract: Palladium‐Catalyzed Asymmetric Hydrosilylation of Styrene and Its Derivatives with Chiral Phosphoramidite Ligands Containing Chiral Ferrocenyl Amine.

AbstractAsymmetric hydrosilylation of styrene and its derivatives (I) is accomplished using a palladium catalyst with the title ligand.

ChemInform Abstract: Chiral Ferrocenyl P,S‐Ligands for Highly Efficient Copper‐Catalyzed Asymmetric [3 + 2] Cycloaddition of Azomethine Ylides

Abstractwith various electron‐deficient olefins giving pyrrole‐type cycloadducts in high endo‐selectivities and excellent enantioselectivities

Enantioselective Synthesis of Ferrocene‐ or Cymantrene‐Fused Planar‐Chiral Phospholes

Planar‐chiral ferrocene‐fused phosphole (S)‐1a was prepared in an enantiomerically pure form by enantioselective transformation. The synthesis was started with Kagan's chiral ferrocenyl acetal (–)‐2a, and bromo and (Z)‐2‐bromovinyl substituents were introduced at the 1‐ and 2‐positions of the ferrocene platform in (S)‐6a with controlling its planar chirality. The double Li/Br exchange on (S)‐6a followed by the reaction with PhPBr2 provided (S)‐1a in excellent yield. The structure of (S)‐1a was determined by X‐ray crystallography. Planar‐chiral cymantrene‐fused phosphole (S)‐1b was also prepared by an analogous asymmetric transformation starting with Jaouen's chiral cymantrenyl acetal (+)‐2b.

(+)-trans-Chlorido-{2-[(Rp)-2-(methyl-sulfan-yl)ferro-cen-yl]-2,5,6,7-tetra-hydro-pyrrolo-[1,2-c]imidazol-3-yl-idene}bis(tri-phenyl-phosphane-κP)palladium(II) hexa-fluorido-phosphate di-chloro-form disolvate.

The title solvated complex, [FePd(C5H5)(C12H13N2S)Cl(C18H15P)2]PF6·2CHCl3, bearing a chiral ferrocenyl pyrrolo-imidazolyl-idene N-heterocyclic carbene (NHC) ligand, was synthesized by oxidative addition of a chloro-imidazolium salt to Pd(PPh3)4. The PdII ion is coordinated in a slightly distorted square-planar coordination geometry, with the Cl atom trans to the coordinating C atom of the pyrrolo-imidazolyl-idene ligand. The complex features a pendant thio-ether group that is not involved in coordination to Pd. In the crystal, weak C-H⋯F and C-H⋯π inter-actions connect the components of the structure, forming chains propagating along [1-10]. The fused pyrrolidine ring is in an envelope conformation, and the flap atom was refined as disordered over two sets of sites, with occupancies of 0.77 (4) and 0.23 (4).

A Family of Chiral Ferrocenyl Diols: Modular Synthesis, Solid-State Characterization, and Application in Asymmetric Organocatalysis.

Readily available chiral diol scaffolds are useful as sources of chirality for asymmetric synthesis, however, few such scaffolds are readily available in enantiopure form. Reported herein is a cheap and modular synthesis of a novel family of chiral ferrocenyl diols in excellent yields with excellent enantio- and diastereoselectivity (>99 % ee and 99 % de). These diols possess not only planar and central chirality, but also axial chirality around the central iron atom. Characterization of these diols by X-ray crystallography revealed intra- and intermolecular hydrogen-bond networks depending on substitution at the carbinol positions. The potential of these diols as catalysts was subsequently demonstrated in an asymmetric hetero-Diels-Alder reaction which provided cycloadducts in up to 84 % yield with ee values ranging from -92 to +72 %.

A Family of Chiral Ferrocenyl Diols: Modular Synthesis, Solid‐State Characterization, and Application in Asymmetric Organocatalysis

AbstractReadily available chiral diol scaffolds are useful as sources of chirality for asymmetric synthesis, however, few such scaffolds are readily available in enantiopure form. Reported herein is a cheap and modular synthesis of a novel family of chiral ferrocenyl diols in excellent yields with excellent enantio‐ and diastereoselectivity (>99 % ee and 99 % de). These diols possess not only planar and central chirality, but also axial chirality around the central iron atom. Characterization of these diols by X‐ray crystallography revealed intra‐ and intermolecular hydrogen‐bond networks depending on substitution at the carbinol positions. The potential of these diols as catalysts was subsequently demonstrated in an asymmetric hetero‐Diels–Alder reaction which provided cycloadducts in up to 84 % yield with ee values ranging from −92 to +72 %.

Chiral Ferrocenyl P,N-Ligands for Palladium-Catalyzed Asymmetric Formal [3 + 2] Cycloaddition of Propargylic Esters with β-Ketoesters: Access to Functionalized Chiral 2,3-Dihydrofurans.

A highly enantioselective palladium-catalyzed [3 + 2] cycloaddition of propargylic esters with β-ketoesters has been realized by employing a newly developed chiral ferrocene/benzimidazole-based P,N-ligand. This protocol features a good tolerance of functional groups in both propargylic esters and β-ketoesters, thereby delivering a variety of highly functionalized chiral 2,3-dihydrofurans bearing an exocyclic double bond at the 3-position in good yields and with high enantioselectivities (up to 98% ee).

Palladium‐catalyzed Asymmetric Hydrosilylation of Styrene and Its Derivatives with Chiral Phosphoramidite Ligands Containing Chiral Ferrocenyl Amine

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Ruthenium-Catalyzed Enantioselective Hydrogenation of Ferrocenyl Ketones: A Synthetic Method for Chiral Ferrocenyl Alcohols.

Highly effective asymmetric hydrogenation of various ferrocenyl ketones, including aliphatic ferrocenyl ketones as well as the more challenging aryl ferrocenyl ketones, was realized in the presence of a Ru/diphosphine/diamine bifunctional catalytic system. Excellent enantioselectivities (up to 99.8% ee) and activities (S/C = 5000) could be obtained. These asymmetric hydrogenations provided a convenient and efficient synthetic method for chiral ferrocenyl alcohols, which are key intermediates for a variety of chiral ferrocenyl ligands and resolving reagents.

ChemInform Abstract: The Design, Synthesis and Application of Imidazolium‐Tagged Ferrocenyl Oxazoline Phosphine Ligands for the Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Nitroalkenes: Ion Effect for Enhancing the Reactivity, Stereoselectivity and Recyclability.

AbstractA series of chiral ferrocenyl oxazoline phosphine ligands is prepared one of which proves valuable for the preparation of substituted pyrrolidine derivatives in high yields, with high to excellent diastereoselectivities and excellent enantioselectivities.