Chiral Bipyridine Research Articles

Coplanar Atropochiral 5H‐Cyclopenta[2,1‐b:3,4‐b']dipyridine Ligands: Synthesis and Applications in Asymmetric Ring‐Opening Reaction

Bipyridines represent a class of ligands renowned for their versatility and efficacy in numerous transition metal‐catalyzed reactions. Chiral bipyridine ligands are noted for their distinctive reactivity and stereoselectivity. In this work, we have designed and synthesized a class of bipyridine ligands endowed with an axially chiral scaffold. These ligands feature: (a) a precisely aligned coplanar bipyridine framework that is beneficial for metal chelation; (b) a spacious environment around the metal‐bipyridine complexes, capable of hosting substrates with substantial steric bulk; (c) a chiral pocket induced by the axially chiral architecture. These atropochiral planar bipyridine ligands were successfully applied in copper‐catalyzed ring‐opening reactions of cyclic diaryliodoniums with bulky secondary amines, achieving high efficiency and stereoselectivity that were unsuccessful in our previous efforts.

Coplanar Atropochiral 5H-Cyclopenta[2,1-b:3,4-b']dipyridine Ligands: Synthesis and Applications in Asymmetric Ring-Opening Reaction.

Bipyridines represent a class of ligands renowned for their versatility and efficacy in numerous transition metal-catalyzed reactions. Chiral bipyridine ligands are noted for their distinctive reactivity and stereoselectivity. In this work, we have designed and synthesized a class of bipyridine ligands endowed with an axially chiral scaffold. These ligands feature: (a) a precisely aligned coplanar bipyridine framework that is beneficial for metal chelation; (b) a spacious environment around the metal-bipyridine complexes, capable of hosting substrates with substantial steric bulk; (c) a chiral pocket induced by the axially chiral architecture. These atropochiral planar bipyridine ligands were successfully applied in copper-catalyzed ring-opening reactions of cyclic diaryliodoniums with bulky secondary amines, achieving high efficiency and stereoselectivity that were unsuccessful in our previous efforts.

Umpolung α-regioselective 1,3-dipolar cycloaddition and internal recycle of byproduct as two key strategies: access to diverse chiral bipyridines

Herein, the first example of umpolung α-regioselective 1,3-dipolar cycloaddition of optically pure perhydroindole-2-carboxylic acid 1a with pyridinecarboxaldehydes 2 is described.

Front Cover: Chiral Bipyridine Ligand with Flexible Molecular Recognition Site: Development and Application to Copper‐Catalyzed Asymmetric Borylation of α,β‐Unsaturated Ketones (ChemCatChem 2/2022)

The Front Cover shows a conceptual art of a novel chiral bipyridine ligand with a flexible hydrogen-bond donor that plays “Harmony” of metal catalysis and multiple non-covalent interactions. In their Communication, R. Tsutsumi et al. applied the newly designed chiral bipyridine ligand to copper-catalyzed asymmetric borylation of α,β-unsaturated ketones. The reaction afforded the corresponding borylated products in high yields with high enantioselectivities through the cooperative action of copper center and hydrogen bonds. Preliminary studies of the functional group-selective transformation revealed that the present chiral bipyridine ligand has the potential of a high-level control of both chemoselectivity and stereoselectivity. More information can be found in the Communication by R. Tsutsumi et al.

Chiral Bipyridine Ligand with Flexible Molecular Recognition Site: Development and Application to Copper‐Catalyzed Asymmetric Borylation of α,β‐Unsaturated Ketones

AbstractA novel chiral bipyridine ligand bearing a flexible side chain with a molecular recognition site enables precise stereocontrol through the cooperative action of metal center and hydrogen bonds. This new chiral ligand was applied to the copper‐catalyzed asymmetric borylation of α,β‐unsaturated carbonyl compounds. The reaction afforded the corresponding borylated products in good yields with high enantioselectivities. Preliminary studies of the functional group‐selective transformation revealed that the newly designed chiral bipyridine ligand has the potential to control chemo‐ and site selectivity in addition to stereoselectivity.

Highly Enantioselective Ring‐Opening of meso‐Epoxides with O‐ and N‐Nucleophiles Catalyzed by a Chiral Sc(III)/bipyridine Complex

AbstractThe ring‐opening of epoxides is a synthetically significant process widely applied in all kinds of chemistry. Herein, we report the catalytic and highly enantioselective variant of this reaction exploiting our recent endeavors to design and synthesize chiral bipyridine type ligands. A Sc‐complex with a newly developed bipyridine ligand exhibited high reactivity and stereocontrol in the desymmetrization of meso‐epoxides with various alcohols. The respective enantiomerically enriched 1,2‐alkoxyalcohols were obtained with e.r. values of up to 99.5:0.5 for various alcohols regardless of their nature (benzyl, alkyl, cycloalkyl, allyl, propargyl, etc.). We attempted ring‐opening of meso‐epoxides with anilines as well; however, it proceeded with lower enantioselectivity and was strongly depended on the electronic effect of substituents attached to the aromatic ring.

Synthesis and Molecular Structure of a Chiral Bipyridine-Menthol Ether

This paper presents the synthesis and structural characterization of 6,6′-bis[(1R,2S,5R)-isomenthoxy]-2,2′-bipyridine obtained by homocoupling of chiral pyridyl-ether 2-bromo-6-[(1R,2S,5R)-isomenthoxy]-pyridine. The two-step synthetic procedure afforded chiral bipyridine in a good yield and the structure of the compound is determined by X-ray diffraction. It crystallizes in a non-centrosymmetric chiral crystal structure type (P2, a = 10.7543(8) A, b = 8.4488(6) A, c = 15.8964(10) A, β = 104.035(7)°, V = 1401.24(17) A3, Z = 2). Moreover, the compound is characterized by FTIR, high resolution mass spectrometry and its complexation capacity to transition metals is studied by UV-Vis spectroscopy.

Synthesis and molecular structure of a chiral bipyridine-menthol ether

This paper presents the synthesis and structural characterization of 6,6'-bis[(1R,2S,5R)-isomenthoxy]-2,2'-bipyridine obtained by homocoupling of chiral pyridyl-ether 2-bromo-6-[(1R,2S,5R)-isomenthoxy]-pyridine. The two-step synthetic procedure afforded chiral bipyridine in a good yield and the structure of the compound is determined by X-ray diffraction. It crystallizes in a non-centrosymmetric chiral crystal structure type (P21, a = 10.7543(8) Å, b = 8.4488(6) Å, c = 15.8964(10) Å, β = 104.035(7)°, V = 1401.24(17) Å3, Z = 2). Moreover, the compound is characterized by FTIR, high resolution mass spectrometry and its complexation capacity to transition metals is studied by UV-Vis spectroscopy.

Z‐bpy, a New C2‐Symmetric Bipyridine Ligand and Its Application in Enantioselective Copper(I)‐Catalyzed Cyclopropanation of Olefins

Summary of main observation and conclusionA rigid C2‐symmetric chiral bipyridine ligand Z‐bpy with a triptycene‐like backbone was designed and synthesized from simple chemicals in a scalable route. Using this new ligand, copper(I) catalyzed cyclopropanation of styrenes with commercial ethyl diazoacetate produced various corresponding cyclopropanes in high yields, diastereoselectivity and enantioselectivity up to 97% ee.

Stereoselective Synthesis of Atropisomeric Bipyridine N,N'-Dioxides by Oxidative Coupling.

Bipyridine N,N'-dioxide is a structural fragment found in many bioactive compounds. Furthermore, chiral analogues secured their place as powerful Lewis base catalysts. The scope of the existing methods for the synthesis of atropisomeric bipyridine N,N'-dioxides is limited. Herein, we present a practical, highly chemo- and stereoselective method for oxidative dimerization of chiral pyridine N-oxides using O2 as a terminal oxidant. A series of 13 axially chiral bipyridine N,N'-dioxides were synthesized in up to 75% yield.

Helical Supramolecular Porphyrin Assemblies

Supramolecular polymers are a class of molecular assemblies, which are held together by non-covalent interactions. Reversible nature of supramolecular polymers results in unique properties such as self-healing and stimuli-responsivity. Therefore, supramolecular polymers have attracted a great deal of interest in material science. A bisporphyrin molecule, where two porphyrin rings are connected with a pyridyl linkage, demonstrates a unique head-to-head homodimeric associationthat is directed through a donor-acceptor interaction and a stacking interaction. A brand-new supramolecular polymer was fabricated by employing this unique supramolecular complex. The two bisporphyrin units needed to be connected with the butadiyne linkage to give rise to a homoditopic tetrakisporphyrin monomer 1. The formation of the self-complementary dimeric bisporphyrin at each end of 1 resulted in the supramolecular helical polymer. In this presentation, we will report the development of the chiral supramolecular polymer that is produced by cross-linking of the supramolecular helical polymer with a chiral bispyridine 2. Figure 1

Synthesis of new bipyridine N,N′-dioxides and their application in asymmetric allylation of benzaldehyde and aldol addition to acetophenone

Two methods for the synthesis of new axially chiral bipyridine N,N′-dioxides based on catalytic [2+2+2] cyclotrimerization of diynes with nitriles were developed. The N,N′-dioxides were used as catalysts in enantioselective allylation of benzaldehyde with allyltrichlorosilane and aldol reaction of trichlorosilyl ketene acetal of methyl acetate with acetophenone.

Structure and photoluminescence of Zn(II) and Сd(II) complexes with chiral bis-pyridine containing fragments of natural (–)-α-pinene

Complexes ZnLCl2 (I) and [CdLCl2] n (IV), where L is chiral bis-pyridine containing fragments of natural monoterpenoide (–)-α-pinene are synthesized. Single crystals of [ZnLCl2]·CH2Cl2 (II), [ZnLCl2]·i-PrOH (III), and IV compounds are grown. The crystal structures of II and III are composed of mononuclear ZnLCl2 complex molecules and solvate CH2Cl2 and i-PrOH molecules; the coordination polyhedron of the zinc atom Cl2N2 is a distorted tetrahedron. According to the single crystal XRD data, complex IV is a 1D coordination polymer; the coordination core CdN2Cl4 is a distorted octahedron and Cl atoms are bridging ligands. In the structures of II, III, and IV the L molecule functions as a bidentate chelate ligand. In the solid phase, complexes I and IV exhibit photoluminescence in the visible range (λmax 505 nm and 460 nm respectively). The band intensity in the photoluminescence spectra of I and IV complexes considerably exceeds the band intensity in the spectrum of free L.

ChemInform Abstract: An Insoluble Copper(II) Acetylacetonate—Chiral Bipyridine Complex that Catalyzes Asymmetric Silyl Conjugate Addition in Water.

Acicular purplish crystals were obtained from Cu(acac)2 and a chiral bipyridine ligand. Although the crystals were not soluble, they nevertheless catalyzed asymmetric silyl conjugate addition of lipophilic substrates in water. Indeed, the reactions proceeded efficiently only in water; they did not proceed well either in organic solvents or in mixed water/organic solvents in which the catalyst/substrates were soluble. This is in pronounced contrast to conventional organic reactions wherein the catalyst/substrates tend to be in solution. Several advantages of the chiral Cu(II) catalysis in water over previously reported catalyst systems have been demonstrated. Water is expected to play a prominent role in constructing and stabilizing sterically confined transition states and accelerating subsequent protonation to achieve high yields and enantioselectivities.

Copper-catalyzed enantioselective C-H functionalization of indoles with an axially chiral bipyridine ligand.

Using copper complexes with an axially chiral bipyridine ligand C4-ACBP as the catalyst, an enantioselective functionalization of indoles with diazo compounds was developed with up to 95% ee. This protocol paves the way for further applications of these ligands.

An Insoluble Copper(II) Acetylacetonate-Chiral Bipyridine Complex that Catalyzes Asymmetric Silyl Conjugate Addition in Water.

Acicular purplish crystals were obtained from Cu(acac)2 and a chiral bipyridine ligand. Although the crystals were not soluble, they nevertheless catalyzed asymmetric silyl conjugate addition of lipophilic substrates in water. Indeed, the reactions proceeded efficiently only in water; they did not proceed well either in organic solvents or in mixed water/organic solvents in which the catalyst/substrates were soluble. This is in pronounced contrast to conventional organic reactions wherein the catalyst/substrates tend to be in solution. Several advantages of the chiral Cu(II) catalysis in water over previously reported catalyst systems have been demonstrated. Water is expected to play a prominent role in constructing and stabilizing sterically confined transition states and accelerating subsequent protonation to achieve high yields and enantioselectivities.

ChemInform Abstract: Conformationally Rigid Chiral Bicyclic Skeleton‐Tethered Bipyridine N,N′‐Dioxide as Organocatalyst: Asymmetric Ring Opening of meso‐Epoxides.

AbstractA new conformationally rigid chiral bipyridine N,N′‐dioxide derivative is synthesized.

Prospects for the Computational Design of Bipyridine N,N′-Dioxide Catalysts for Asymmetric Propargylation Reactions

Stereoselectivities were predicted for the allylation of benzaldehyde using allyltrichlorosilanes catalyzed by 18 axially chiral bipyridine N,N′-dioxides. This was facilitated by the computational toolkit AARON (Automated Alkylation Reaction Optimizer for N-oxides), which automates the optimization of all of the required transition-state structures for such reactions. Overall, we were able to predict the sense of stereoinduction for all 18 of the catalysts, with predicted ee’s in reasonable agreement with experiment for 15 of the 18 catalysts. Curiously, we find that ee’s predicted from relative energy barriers are more reliable than those based on either relative enthalpy or free energy barriers. The ability to correctly predict the stereoselectivities for these allylation catalysts in an automated fashion portends the computational screening of potential organocatalysts for this and related reactions. By studying a large number of allylation catalysts, we were also able to gain new insight into the origin of stereoselectivity in these reactions, extending our previous model for bipyridine N-oxide-catalyzed alkylation reactions (Organic Letters 2012, 14, 5310). Finally, we assessed the potential performance of these bipyridine N,N′-dioxide catalysts for the propargylation of benzaldehyde using allenyltrichlorosilanes, finding that two of these catalysts should provide reasonable stereoselectivities for this transformation. Most importantly, we show that bipyridine N,N′-dioxides constitute an ideal scaffold for the development of asymmetric propargylation catalysts and, along with AARON, should enable the rational design of such catalysts purely through computation.

Iron(II)‐Derived Lewis Acid/Surfactant Combined Catalysis for the Enantioselective Mukaiyama Aldol Reaction in Pure Water

AbstractThe catalytic asymmetric Mukaiyama aldol reaction in pure water was performed by using a combination of iron(II) dodecyl sulfate, a chiral bipyridine ligand, and benzoic acid. By using the obtained iron(II)‐derived Lewis acid/surfactant combined catalyst, the desired products were afforded in good yields with high diastereo‐ and enantioselectivities.

ChemInform Abstract: Highly Enantioselective Iron(II)‐Catalyzed Opening Reaction of Aromatic meso‐Epoxides with Indoles.

AbstractUnprecedented high enantioselectivities are obtained in the ring opening of cis‐stilbene oxide (II) with indoles (I) using iron perchlorate and a chiral bipyridine ligand as catalyst system.