Planar Chiral Ligands Research Articles

Synthesis of planar chiral ferrocenes via enantioselective remote C-H activation.

Planar chiral ferrocenes are widely studied structures in asymmetric catalysis, materials science and medicinal chemistry. Although synthetic methods for 1,2-disubstituted planar chiral ferrocenes are well known, methods for the direct construction of 1,3-disubstituted planar chiral ferrocenes remain elusive. Here we report a modular platform for the construction of planar chirality in 1,3-disubstituted ferrocenes/ruthenocenes via an enantioselective relay remote C-H activation strategy. This method demonstrates a mechanism for remote enantiocontrol via enantiodetermining initial C‒H activation at the C2 position, enabled by a chiral mono-N-protected natural amino-acid ligand, and subsequent relay to the remote C3 position by a bridgehead-substituted norbornene mediator. A wide variety of 1,3-disubstituted planar chiral metallocenes are prepared with high enantioselectivity (96‒99% e.e.). The reaction shows good functional-group tolerance and high step-economy, and aryl iodides/bromides are compatible as coupling partners. The resulting metallocenes can be readily derivatized to yield planar chiral ligands and catalysts for asymmetric catalysis as well as building blocks for other applications.

Temperature-Controlled Divergent Asymmetric Synthesis of Indole-Based Medium-Sized Heterocycles through Palladium Catalysis

The divergent construction of chiral medium-sized rings is an essential but challenging task in organic synthesis. Herein, we report a temperature-controlled catalytic system for the divergent, enantioselective synthesis of different types of medium-sized rings starting from the same substrate set. Enabled by a planar chiral bisphosphine ligand, the palladium-catalyzed (5 + 4) and formal (5 + 2) annulations of cyclic aza-dienes and vinylethylene carbonates proceeded smoothly to afford a broad spectrum of indole-based medium-sized heterocycles in excellent yields with outstanding enantioselectivities. Those products could be further diversified through various functional group transformations. Moreover, mechanistic studies, including control experiments and DFT calculations, shed light on understanding the observed regio- and enantioselectivities of palladium-catalyzed (5 + n) cyclization.

Design and synthesis of a new family of planar and central chiral ferrocenyl phosphine ligands.

A family of planar chiral indene-fused ferrocenes were prepared through an intramolecular asymmetric C-H arylation in excellent yields (up to 99%) with excellent enantioselectivities (up to 99% ee). They were thereafter successfully transformed to chiral ferrocenyl phosphines, featuring both planar and central chiralities, in good yields (up to 83%) and excellent diastereoselectivities (up to 99% de) through highly diastereoselective phosphination. This protocol offers a general method for planar and central chiral ferrocenyl phosphines. The potential applications of the newly developed ligands were demonstrated by a Pd-catalyzed enantioselective allylic alkylation reaction, in which high enantioselectivity (92% ee) and good yield (89%) were obtained.

Synthesis and Evaluation of Novel Planar‐Chiral Monophosphine Ligands Bearing Ferrocene‐Triazole Backbones

We prepared novel planar chiral monophosphine ligands bearing ferrocene-triazole backbones. These ligands were produced in a series of steps that included triazole synthesis by diastereoselective azidation and Huisgen cycloaddition of (S)-Ugi's amine, followed by methylation and phosphine introduction. This method was applicable to the preparation of various analogues due to the wide substrate scope of the Huisgen cycloaddition reaction. These ligands showed good catalytic activity in Suzuki–Miyaura coupling reactions, especially those involving bulky substrates. Furthermore, the optically active versions of these ligands were used in the asymmetric Suzuki–Miyaura coupling reaction to produce the axial chiral binaphthyl compound with moderate enantioselectivity. The ligand developed in this study is the first triazole-type biaryl- monophosphine ligand that can be used in asymmetric reactions, and it is expected to be a new tool for the accessing chiral compounds.

Rhodium catalysts derived from a fluorinated phanephos ligand are highly active catalysts for direct asymmetric reductive amination of secondary amines

Abstract An asymmetric hydrogenation of enamines is efficiently catalysed by rhodium complexed with a fluorinated version of the planar chiral paracyclophane-diphosphine ligand, Phanephos. This catalyst was shown to be very active, with examples operating at just 0.1 mol% of catalyst. This catalyst was then successfully adapted to Direct Asymmetric Reductive Amination, leading to the formation of several tertiary amines with moderate ee, if activated ketone/amine partners are used.

Controlling Regioselectivity in Palladium-Catalyzed C-H Activation/Aryl-Aryl Coupling of 4-Phenylamino[2.2]paracyclophane.

Selective activation/functionalization of C−H bonds has emerged as an atom‐ and step‐economical process at the forefront of modern synthetic chemistry. This work reports palladium‐catalyzed exclusively para‐selective C−H activation/aryl–aryl bond formation with a preference over N‐arylation under the Buchwald–Hartwig amination reaction of 4‐phenylamino[2.2]paracyclophane. This innovative synthetic strategy allows a facile preparation of [2.2]paracyclophane derivatives featuring disparate para‐substitutions at C‐4 and C‐7 positions in a highly selective manner, gives access to a series of potential candidates for [2.2]paracyclophane‐derived new planar chiral ligands. The unprecedented behavior in reactivity and preferential selectivity of C−C coupling over C−N bond formation via C−H activation is unique to the [2.2]paracyclophane scaffold compared to the non‐cyclophane analogue under the same reaction conditions. Selective C−H activation/aryl–aryl bond formation and sequential C−N coupling product formation is evidenced unambiguously by X‐ray crystallography.

Synthesis of a Mechanically Planar Chiral Rotaxane Ligand for Enantioselective Catalysis

SummaryRotaxanes are interlocked molecules in which a molecular ring is trapped on a dumbbell-shaped axle because of its inability to escape over the bulky end groups, resulting in a so-called mechanical bond. Interlocked molecules have mainly been studied as components of molecular machines, but the crowded, flexible environment created by threading one molecule through another has also been explored in catalysis and sensing. However, so far, the applications of one of the most intriguing properties of interlocked molecules, their ability to display stereogenic units that do not rely on the stereochemistry of their covalent subunits, termed “mechanical chirality,” have yet to be properly explored, and prototypical demonstration of the applications of mechanically chiral rotaxanes remain scarce. Here, we describe a mechanically planar chiral rotaxane-based Au complex that mediates a cyclopropanation reaction with stereoselectivities that are comparable with the best conventional covalent catalyst reported for this reaction.

Development of Planar Chiral Five-Membered Cyclic (Amino)(ferrocenylene)carbene Ligand and Its Iridium Dicarbonyl Complex

AbstractA five-membered cyclic (amino)(ferrocenylene)carbene (CAFeC) ligand was developed as the counterpart of existing seven- and six-membered planar chiral CAFeC ligands to enrich the series. The novel CAFeC was subjected to carbene trapping experiments with sulfur and an iridium complex. The resulting sulfur adduct and Ir dicarbonyl complex were fully characterized by X-ray diffraction analysis, high-resolution mass spectrometry, and multinuclear NMR spectroscopy. The Tolman electronic parameter (TEP) of the Ir dicarbonyl complex revealed that the donor strength of the new CAFeC is high, as expected.

Copper-Mediated Diastereoselective C–H Thiolation of Ferrocenes

The first copper-mediated diastereoselective C–H thiolation of ferrocenes has been developed. A chiral oxazoline directing group with tert-butyl substituent is essential to the high diastereoselectivity ratio and the suppression of overreaction of monothiolated products. This reaction tolerated various functional groups on arylthiols, implying its potential application in N,S-bidentate planar chiral ligands.

Stereoselective and Stereospecific Reactions of Cobalt Sandwich Complexes: Synthesis of a New Class of Single Enantiomer Bulky Planar Chiral P-N and P-P Ligands.

Starting from (η5 -acetylcyclopentadienyl)(η4 -tetraphenylcyclobutadiene)cobalt(I), highly enantioselective (99 % ee) (S)-CBS catalysed ketone reduction followed by stereospecific alcohol-azide exchange, azide reduction and dimethyllation gave (R)-(η5 -α-N,N-dimethylaminoethylcyclopentadienyl)(η4 -tetraphenylcyclobutadiene) cobalt(I) (Arthurs' amine). This underwent highly diastereoselective cyclopalladation to give di-μ-acetate-bis-(R)-[(η5 -(Sp )-2-(α-N,N-dimethylaminoethyl)cyclopentadienyl, 1-C, N)(η4 -tetraphenylcyclobutadiene)cobalt(I)]dipalladium, and highly diastereoselective lithiation to give (R)-(η5 -(Sp )-1-(α-N,N-dimethylaminoethyl)-2-(diphenylphosphino)cyclopentadienyl)(η4 -tetraphenylcyclobutadiene)cobalt(I) (PPCA) following the addition as electrophile of chlorodiphenylphosphine. This PN-ligand was converted into (R)-(η5 -(Sp )-1-(α-dicyclohexylphosphinoethyl)-2-(diphenylphosphino)cyclopentadienyl)(η4 -tetraphenylcyclobutadiene)cobalt(I), a PP-ligand (Rossiphos), by stereospecific amine-phosphine exchange using HPCy2 . These air-stable P-N and P-P complexes are the first examples of a new class of bulky planar chiral ligands for application in asymmetric catalysis.

Planar chiral [2.2]paracyclophanes: from synthetic curiosity to applications in asymmetric synthesis and materials.

Planar chiral [2.2]paracyclophane-based ligands and employment of such enantiopure representative ligands to facilitate selective transformation of prochiral or racemic substances into enantiopure products are rarely explored compared to the complex chiral scaffolds such as ferrocenes. This tutorial discusses recent findings and inspiring progress in design, synthetic tunability and applications of planar chiral [2.2]paracyclophane systems as a practical class of catalysts for asymmetric synthesis. Here, we summarize a series of planar chiral [2.2]paracyclophanes that are becoming an important new tool-box in asymmetric synthesis, employed in a variety of synthetic venues such as new chiral ligands and catalysts for stereo-controlled and enantioselective addition of alkyl, alkenyl, alkynyl and aryl zinc reagents to aliphatic and aromatic aldehydes, ketones, imines and many more. Besides, planar chiral [2.2]paracyclophanes are useful synthons, from a material perspective, can be incorporated into conjugated polymeric systems for chiroptical and optoelectronic properties, find broad applications in bio- and materials science, for instance, gold-based cytostatics, surface-mounted chiral MOF thin films for selective adsorption or in functionalized parylene polymer coatings, to name a few. This is an up-to-date tutorial review, written exclusively on planar chiral [2.2]paracyclophane chemistry, covering key aspects of synthesis, structures, properties, applications and future directions of chiral polymeric assemblies and novel biomaterials built with [2.2]paracyclophanes.

Synthesis, Coordination and Catalytic Tests of New Chiral ferrocenyl P,N ligands

Many efforts have been devoted to the development of asymmetric catalysis because of the significant use of chiral compounds as intermediates of pharmaceuticals and advanced materials.[1] Amongst many ligands which have been tested, planar chiral ferrocenes ligands constitutes a privileged family of ligands for enantioselective catalysis.[2] We will disclose in this communication the synthesis of a new chiral N-(p-toluenesulfonyl)-containing ferrocenyl ligands and its coordination chemistry with Ru, Ir and Rh precursors yielding in some cases chiral at metal complexes. [3] Moreover, DFT calculations in order to better understand the nature and stabilities of these complexes will be presented. Additionally, preliminary evaluation of the different complexes as catalysts for the asymmetric transfer hydrogenation of ketones will also be disclosed.

ChemInform Abstract: The Design and Synthesis of Planar Chiral Ligands and Their Application to Asymmetric Catalysis

AbstractReview: [49 refs.

Sterically Demanding Planar Chiral P,N Ligands by Diastereoselective Ortho Lithiation of Pentaphenylferrocenyloxazolines and Their Application to Palladium-Catalyzed Substitutions with Cyclic Allylic Acetates

Functionalized 1′,2′,3′,4′,5′-pentaphenylferrocenes are known as valuable ligands and catalysts. Planar chiral derivatives—e.g. Fu’s pentaphenylferrocene fused pyridines or palladacycles developed in our group—have previously been described to be very efficient asymmetric catalysts for a number of applications. Nevertheless, protocols for diastereoselective ortho lithiations of 1′,2′,3′,4′,5′-pentaphenylferrocenes are still unknown. Such protocols could significantly increase the arsenal of accessible planar chiral pentaphenylferrocenes. In this full paper, we describe such diastereoselective ortho lithiations of pentaphenylferrocenyloxazolines. Both possible diastereomers can be produced in almost diastereomerically pure form depending on the choice of a Lewis base additive, which is required in the lithiation step for a sufficient reactivity. This development was utilized to prepare a set of planar chiral pentaphenylferrocene-based phosphino-oxazoline ligands. The latter were investigated in Pd-catalyzed allylic substitution reactions with cyclic allylic acetates to allow for a first comparison with related planar chiral ligands and provided good enantioselectivity with this challenging substrate class.

The Design and Synthesis of Planar Chiral Ligands and Their Application to Asymmetric Catalysis

Ferrocene- and ruthenocene-based planar chiral ligands have been developed and used in transition-metal-catalyzed asymmetric allylic substitutions, asymmetric hydrogenations, and asymmetric conjugate addition reactions. The most common ferrocene ligands, which have bis(oxazoline) substituents on the cyclopentadiene rings, have been modified to create new planar chiral C 2-symmetric ligands, some of which have shown excellent potential in the aforementioned reactions. A series of planar chiral ruthenocene ligands have also been developed and their activities differ from those of their ferrocene counterparts. 1 Introduction 2 The Design and Synthesis of Planar Chiral Ligands 2.1 Ferrocene-Based Ligands 2.2 Ruthenocene-Based Ligands 3 Applications of Planar Chiral Ligands in Asymmetric Reactions 3.1 Asymmetric Allylic Alkylation 3.2 Asymmetric Allylic Amination 3.3 Asymmetric Allylic Alkylation with Enamines as Nucleophiles 3.4 Asymmetric Alkylation of Aryl Aldehydes 3.5 Asymmetric Hydrogenation 3.6 1,4-Asymmetric Conjugation Reactions 4 Summary

Iridium and rhodium complexes with the planar chiral thioether ligands in asymmetric hydrogenation of ketones and imines

Rhodium complexes with the planar chiral phosphinoferrocenyl thioether ligands [Rh(P,SR)(diene)X] (R = Me, But, Ph, Bn, diene is cyclooctadiene (COD) or norbornadiene (NBD), X = Cl, BF4) catalyze hydrogenation of ketones, imines, and heteroaromatic compounds; in the case of acetophenone, the enantioselectivity reached 60% ee. Similar iridium complexes demonstrate a good activity in the hydrogenation of imines, the maximal enantioselectivity in the case of N-phenyl-N-(1-phenylethylidene)amine was about 40% ee.

Asymmetric NH Insertion Reaction Cooperatively Catalyzed by Rhodium and Chiral Spiro Phosphoric Acids

Nitrogen-containing organic compounds, such as a-amino acids and alkaloids, are important biologically active compounds, thus the development of efficient and enantioselective methods for the construction of carbon–nitrogen bonds is a fundamental goal in modern organic synthesis. Transitionmetal-catalyzed carbene insertion into N H bonds is one of the most efficient methods to construct carbon–nitrogen bonds and the development of asymmetric versions of the N H insertion reaction has attracted considerable attention. In initial studies, chiral dirhodium catalysts were tested in intramolecular and intermolecular N H insertion reactions, however, only low to modest enantioselectivities (< 50% ee) were achieved. Since these reports, other transition metals including copper and silver have been used as catalysts, and gave enantioselectivities up to 48% ee. Recently, we reported a highly enantioselective N H insertion reaction (up to 98% ee) using a copper complex with chiral spiro bisoxazoline ligands. Subsequently, two other types of chiral copper catalysts have been developed, one with a planar chiral bipyridine ligand and the other with a binolderivative ligand, and both of these catalysts give high enantioselectivities in N H insertion reactions. Although progress on copper-catalyzed asymmetric N H insertion reactions has been substantial, they still have serious limitations. For instance, all the copper-catalyzed N H insertion reactions require high catalyst loading (5– 10 mol%) for satisfactory yields and enantioselectivities, thus more-efficient chiral catalysts are highly desirable. Because the activity of dirhodium(II) catalysts is usually superior to that of copper catalysts in nonenantioselective N H insertion reactions, the possibility of using dirhodium catalysts to achieve highly enantioselective N H insertion reactions is an intriguing one. Recently, Saito et al. reported that dirhodium(II) carboxylates and cinchona alkaloids cooperatively catalyze the asymmetric N H insertion reactions of a-diazo-a-arylacetates with anilines. The combined catalysts exhibit excellent reactivity but only modest enantioselectivity (up to 71% ee). It is generally accepted that the rhodium-catalyzed N H insertion most likely proceeds via an ylide intermediate (Scheme 1A). We speculated that the subsequent protontransfer step could be facilitated by a chiral phosphoric acid species via a seven-membered-ring transition state, and that, consequently, chiral induction could be accomplished in this step (Scheme 1B). The groups of Yu and Platz have reported that either water or alcohols can assist proton transfer in O H insertion reactions, as indicated by density functional theory calculations and ultrafast time-resolved IR spectroscopy studies. These studies stimulated our interest in exploring asymmetric N H insertion in the presence of a proton-transfer catalyst. As part of our ongoing work on the development of asymmetric carbene insertion reactions, we report herein the asymmetric N H insertion reaction cooperatively catalyzed by dirhodium(II) carboxylates and chiral spiro phosphoric acids (SPAs). Excellent reactivity and high enantioselectivity (up to 95% ee) were achieved in the presence of as little as 0.1 mol% of catalyst. In our initial study, we carried out the insertion of methyl a-diazo-a-phenylacetate (3a) into the N H bond of tert-butyl carbamate (BocNH2) in CHCl3 at 25 8C using 1 mol% of [Rh2(OAc)4] and 10 mol% of chiral SPAs 1 as the catalysts (Table 1). SPAs 1 were prepared by a simple condensation of P(O)Cl3 with 6,6’-disubstituted-1,1’-spirobiindane-7,7’-diols 2, followed by hydrolysis (Scheme 2). Diols 2 were synthesized from spinol (1,1’-spirobiindane-7,7’-diol), as described previously. In the presence of (R)-1a, the N H insertion reaction proceeded within 5 minutes to afford the insertion product in excellent yield with 11% ee (Table 1, entry 2). Control experiments showed that the SPAs alone did not promote the insertion reaction. A range of SPAs with various substituents at the 6 and 6’ positions were evaluated (Table 1, entries 3–9). All the tested SPAs afforded high yields in the N H insertion reaction. SPA (R)-1h, which bears a 6,6’-di(naphth-2-yl) group, afforded the Scheme 1. Proposed mechanism for chiral phosphoric acid induced asymmetric N H insertion.

ChemInform Abstract: Palladium‐Catalyzed Asymmetric Hydrosilylation of 1,3‐Dienes

AbstractReview: 41 refs.

New cyclopentadienylethylphosphane chelate complexes with unsymmetrical phosphane substitution

The syntheses, characterization, and some reactions of (phosphanylethyl)cyclopentadienyl chelate complexes of cobalt, rhodium, iridium, nickel, and chromium with unsymmetrical substitution at the phosphorus atom are described. The ligand systems were prepared by nucleophilic ring opening of spiro[2.4]hepta-4,6-diene with lithium tert-butylphenylphosphide or lithium tert-butylcyclohexylphosphide. The anionic ligands give the respective chelate complexes by treatment with metal halide reagents. In three cases it was possible to obtain X-ray crystal structure analyses. The cobalt chelate complex undergoes oxidative addition with a dihydrosilane, the reaction results in the formation of products with three stereogenic centers at phosphorus, cobalt, and silicon, which show dynamic behavior as indicated by VTNMR. The rhodium chelate complex undergoes oxidative addition of iodomethane with diastereoselective formation of the respective Rh(III) chelate. While diastereoselectivity caused by a planar chiral indenyl ligand or by a stereogenic carbon center in the chelate backbone has earlier been observed, this is the first case of a stereoinduction by the stereogenic phosphorus ligand. Activation energies for the rotation of cobalt and rhodium chelates have also been determined by VTNMR.

Synthesis of new planar chiral [2.2]paracyclophane Schiff base ligands and their application in the asymmetric Henry reaction

A series of new planar and central chiral ligands based on [2.2]paracyclophane backbones were designed and prepared from enantiomerically pure 4-amino-13-bromo[2.2]paracyclophane and commercially available chiral amino alcohols. Their application in a copper-catalyzed asymmetric Henry reaction resulted in secondary alcohols with high yield and excellent selectivity for active aldehydes (up to 94% ee). This is a successful example of employing planar chiral [2.2]paracyclophane ligands in copper-catalyzed reaction.