Pybox Ligand Research Articles

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids: Construction of Oxindoles Bearing Quaternary Carbons

We have developed a nickel- nickel/bisphosphine-catalyzed stereoconvergent cross-coupling reaction of epoxides with alkenylboronic acids. Racemic spiroepoxyoxindoles were converted to chiral homoal...

Enantioselective Cu(I)-Catalyzed Cycloaddition of Prochiral Diazides with Terminal or 1-Iodoalkynes.

We report an unprecedented highly enantioselective desymmetric Cu(I)-catalyzed 1,3-dipolar cycloaddition of diazides with terminal alkynes and 1-iodoalkynes, affording tertiary alcohols bearing a 1,2,3-triazole moiety in high yield and excellent ee value. PYBOX ligands with a C4 shielding group once again show the promising ability to achieve higher enantioselectivity.

Cover Feature: Lanthanum‐Catalyzed Enantioselective Trifluoromethylation by Using an Electrophilic Hypervalent Iodine Reagent (Chem. Eur. J. 35/2019)

La La Ligand! Lanthanum(III) complexes incorporating enantiopure PyBOX ligands are suitable catalysts for the enantioselective trifluoromethylation of β-oxo esters in the presence of hypervalent iodine Togni reagent. DFT calculations reveal that the enantioselectivity of the reaction stems from the rigid coordination pattern around the metallic center that results in the efficient blockage of one of the prochiral faces of the intermediate LaIII enolate. More information can be found in the Communication by F. P. Cossío, A. Vallribera, et al. on page 8214.

Iron(III)/Copper(II)-Cocatalyzed Cycloaddition/[3,3]-Rearrangement/N-O Bond Cleavage To Prepare Polysubstituted Pyrrolizines from N-Vinyl-α,β-Unsaturated Nitrones and Activated Alkynes.

An efficient one-pot synthesis of polysubstituted pyrrolizines from N-vinyl- α,β-unsaturated nitrones and activated alkynes through iron(III)/copper(II)-cocatalyzed [3 + 2] cycloaddition/[3,3]-rearrangement and sequential N-O bond cleavage was developed. The reaction first underwent [3 + 2] cycloaddition and [3,3]-rearrangement to afford nine-membered N-heterocycles, and then a controlled N-O bond cleavage of nine-membered rings by iron(III)/copper(II) cocatalysts delivered pyrrolizine scaffolds. A kinetic resolution of nine-membered ring compounds was achieved for the first time by using copper(II) acetate combined with a chiral PyBox ligand.

Synthesis of zinc(II) complex-containing thermo-responsive copolymer based on activated ester functionalization and its catalysis application

In this study, we report the synthesis of pybox zinc(II) complex-containing thermo-responsive copolymer through activated ester strategy and their application in Knoevenagel condensation as an efficient and recoverable catalyst. First, a series of thermo-responsive copolymers P(MASI-co-DEGMMA-co-OEGMMA300) of activated ester monomer N-methacryloxysuccinimide (MASI), ethylene glycol methyl ether methacrylate (DEGMMA) and oligo(ethylene glycol) methacrylate (OEGMMA300) were synthesized through free-radical copolymerization using azodiisobutyronitrile (AIBN) as an initiator in solution polymerization. The lower critical solution temperature (LCST) of the P(MASI-co-DEGMMA-co-OEGMMA300) copolymers was controlled by adjusting the mole fractions of the monomers. The synthesized copolymers were well characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), infrared spectrum (FTIR) and gel permeation chromatography (GPC). Then, pybox ligand with a terminal amino group was introduced into P(MASI-co-DEGMMA-co-OEGMMA300) based on activated ester functionalization, and further coordinate with ZnCl2 to afford a pybox zinc(II) complex-containing thermo-responsive copolymer. The zinc complex-containing polymer displayed excellent catalytic activities for Knoevenagel condensation reaction in water at room temperature, and it can be easily recovered by centrifugation at a higher temperature, above the LCST of the copolymer after reaction. The recovered catalyst can be reused at least five cycles without obvious decrease in catalytic activity.

Nickel‐Catalyzed Enantioconvergent Borylation of Racemic Secondary Benzylic Electrophiles

AbstractNickel‐catalyzed cross‐coupling has emerged as the most versatile approach to date for achieving enantioconvergent carbon–carbon bond formation using racemic alkyl halides as electrophiles. In contrast, there have not yet been reports of the application of chiral nickel catalysts to the corresponding reactions with heteroatom nucleophiles to produce carbon–heteroatom bonds with good enantioselectivity. Herein, we establish that a chiral nickel/pybox catalyst can borylate racemic secondary benzylic chlorides to provide enantioenriched benzylic boronic esters, a highly useful family of compounds in organic synthesis. The method displays good functional group compatibility (e.g., being unimpeded by the presence of an indole, a ketone, a tertiary amine, or an unactivated alkyl bromide), and both of the catalyst components (NiCl2⋅glyme and the pybox ligand) are commercially available.

Nickel-Catalyzed Enantioconvergent Borylation of Racemic Secondary Benzylic Electrophiles.

Nickel-catalyzed cross-coupling has emerged as the most versatile approach to date for achieving enantioconvergent carbon-carbon bond formation using racemic alkyl halides as electrophiles. In contrast, there have not yet been reports of the application of chiral nickel catalysts to the corresponding reactions with heteroatom nucleophiles to produce carbon-heteroatom bonds with good enantioselectivity. Herein, we establish that a chiral nickel/pybox catalyst can borylate racemic secondary benzylic chlorides to provide enantioenriched benzylic boronic esters, a highly useful family of compounds in organic synthesis. The method displays good functional group compatibility (e.g., being unimpeded by the presence of an indole, a ketone, a tertiary amine, or an unactivated alkyl bromide), and both of the catalyst components (NiCl2 ⋅glyme and the pybox ligand) are commercially available.

Titanium and vanadium catalysts with oxazoline ligands for ethylene-norbornene (co)polymerization

A series of catalysts, (Py-ox)TiCl4, (Py-box)TiCl4, (Py-ox)VCl3, (Py-box)VCl3, SIL/(Py-ox)VCl3, SIL/(Py-box)VCl3, with 2-(1,3-oxazolin-2-yl)pyridine (Py-ox) and 2,6-bis(1,3-oxazolin-2-yl)pyridine (Py-box) ligands, silica support modified by 1-[3-(triethoxysilyl)propyl]pyridinium ethylchloroaluminate ionic liquid (SIL), activated by AlEt2Cl, AlEtCl2, and methylaluminoxane (MMAO) were studied in ethylene polymerization and ethylene-norbornene copolymerization. Single-crystal X-ray diffraction is given for both Py-ox and Py-box. The complexation was confirmed by NMR and ESI-MS methods. All complexes were found to be active in ethylene polymerization with better performance of the vanadium catalysts. Properties of polyethylene (PE) obtained using these catalysts are characterized by the molecular weight (Mw) within the range of 1.5–2.4 × 106 g/mol, narrow molecular weight distribution (1.9 < Mw/Mn < 2.9), melting temperature (131 < Tm < 144 °C), and crystallinity degree (42 < X < 81%). The sup.ported SIL/(Py-box)VCl3 catalyst activated by AlEt2Cl shows the best activity in ethylene polymerization (8120 kg PE/molV h) and copolymerization with norbornene (7135 kg Cop/molV h). The vanadium systems show high norbornene (NB) incorporation within the range of 17–40 mol% at low NB concentration (0.5–1.5 mol/L). Copolymer is characterized by Mw from 107 to 960 × 103 g/mol and narrow Mw/Mn (1.6–2.6). Glass transition temperature (Tg up to 61 °C) depends linearly on the amount of comonomer incorporated.

Copper-Catalyzed Stereo- and Enantioselective 1,4-Protosilylation of α,β-Unsaturated Ketimines To Synthesize Functionalized Allylsilanes

Copper-catalyzed conjugate protosilylation reaction of α,β-unsaturated sulfonyl ketimines has been developed. The corresponding E- and Z-stereoselective functionalized allylsilane products were obtained in good yields respectively via tuning the ligands used in the reactions. Furthermore, the highly enantioselective (E)-β-tosylamine-substituted allylsilanes were also achieved in the presence of chiral Pybox ligand. And the corresponding products could be easily transformed into other useful synthons.

Efficient Synthesis of N-Alkylated 4-Pyridones by Copper-Catalyzed Intermolecular Asymmetric Propargylic Amination.

Copper-catalyzed intermolecular asymmetric propargylic amination with 4-hydroxypyridines has been realized for the first time. In the presence of Cu complex derived from Pybox ligand, the N-propargylated 4-pyridones were obtained under mild reaction conditions with up to 99 % yield and 95 % ee. The Pybox ligand bearing a 4-F-phenyl substituent plays a key role for the high enantioselectivity. The products can be easily transformed to the core structure of quinolizidine alkaloids.

Lanthanum-pyBOX complexes as catalysts for the enantioselective conjugate addition of malonate esters to β,γ-unsaturated α-ketimino esters

In this paper, we report the application of chiral complexes of La(III) with pyBOX ligands as Lewis acid catalysts in the conjugate addition of malonic esters to N-tosyl imines derived from β,γ-unsaturated α-keto esters to give the corresponding chiral α,β-dehydroamino esters. pyBOX complexes with La(III), Yb(III), Sc(III), and In(III) triflates were assessed in this reaction but only La(III) showed good activity and enantioselectivity, while Yb(III) provided the expected product with low yield and stereoselectivity, and the Sc(III) and In(III) complexes were completely inactive. The complex of La(OTf)3 with the diphenyl-pyBOX ligand prepared in situ provided the best results and allowed obtaining chiral α,β-dehydroamino esters 3 with excellent yields, E:Z diastereomeric ratios (29:71–99:1) and high enantiomeric excesses (20–95%). The reaction could be applied to imines having a substituted aromatic ring or a heterocycle attached to the double bond, although the presence of electron-withdrawing groups on the aromatic ring was detrimental for stereoselectivity. The reaction products were obtained with the S configuration at the stereogenic center and the Z configuration at the enamine double bond as determined by NOESY experiments and X-ray analysis. Based on the experimental results a stereochemical model involving a nine-coordinate La(III) species has been proposed.

The Asymmetric Friedel‐Crafts Reaction of Indoles with Arylidenemalonates Catalyzed by MgI2/PyBox Complexes

AbstractA mild and efficient catalytic enantioselective addition of indoles to dimethyl arylidenemalonates using MgI2 and PyBOX ligands bearing halogen substituents has been elaborated. The reactions were conducted in DCM at low temperature generally providing high yields (up to 99%), while enantioselectivity was shown to be strongly dependent on the nature of substituents in arylidenemalonate and indole reaching 83% ee. The reactivity of arylidenemalonates under described conditions was found to be enough different from that in copper‐catalyzed Friedel‐Crafts alkylation.

Chiroptical methods in a wide wavelength range for obtaining Ln3+ complexes with circularly polarized luminescence of practical interest.

We studied enantiopure chiral trivalent lanthanide (Ln3+ = La3+, Sm3+, Eu3+, Gd3+, Tm3+, and Yb3+) complexes with two fluorinated achiral tris(β-diketonate) ligands (HFA = hexafluoroacetylacetonate and TTA = 2-thenoyltrifluoroacetonate), incorporating a chiral bis(oxazolinyl)pyridine (PyBox) unit as a neutral ancillary ligand, by the combined use of optical and chiroptical methods, ranging from UV to IR both in absorption and circular dichroism (CD), and including circularly polarized luminescence (CPL). Ultimately, all the spectroscopic information is integrated into a total and a chiroptical super-spectrum, which allows one to characterize a multidimensional chemical space, spanned by the different Ln3+ ions, the acidity and steric demand of the diketone and the chirality of the PyBox ligand. In all cases, the Ln3+ ions endow the systems with peculiar chiroptical properties, either allied to f-f transitions or induced by the metal onto the ligand. In more detail, we found that Sm3+ complexes display interesting CPL features, which partly superimpose and partly integrate the more common Eu3+ properties. Especially, in the context of security tags, the pair Sm/Eu may be a winning choice for chiroptical barcoding.

Cover Picture: Secondary Phosphine Oxide Preligands for Palladium-Catalyzed C-H (Hetero)Arylations: Efficient Access to Pybox Ligands (Adv. Synth. Catal. 18/2017)

Cover Picture: Secondary Phosphine Oxide Preligands for Palladium-Catalyzed C-H (Hetero)Arylations: Efficient Access to Pybox Ligands (Adv. Synth. Catal. 18/2017)

Asymmetric Synthesis of 3‐Allyloxindoles and 3‐Allenyloxindoles by Scandium(III)‐Catalyzed Claisen Rearrangement Reactions

Scandium‐catalyzed asymmetric Claisen rearrangement reactions of 2‐allyloxyindoles and 2‐propargyloxyindoles provide a novel approach to diverse 3‐allyloxindoles and 3‐allenyloxindoles in excellent yields (up to 99%) and enantioselectivity (up to 99% ee) under mild reaction conditions. The scandium catalyst was derived from Sc(OTf)3 and Pybox ligand.

Secondary Phosphine Oxide Preligands for Palladium‐Catalyzed C–H (Hetero)Arylations: Efficient Access to Pybox Ligands

AbstractC–H arylations of oxazolines were accomplished with a well‐defined palladium catalyst derived from a secondary bisdiamantyl phosphine oxide. The single‐component secondary phosphine oxide (SPO)‐palladium complex enabled C–H activations with aryl bromides and challenging aryl chlorides in the absence of directing groups, setting the stage for the step‐economical synthesis of pybox ligands under racemization‐free reaction conditions.magnified image

Lewis Acid Catalyzed [3+3] Annulation of Donor–Acceptor Cyclopropanes with γ‐Hydroxyenones: Access to Highly Functionalized Tetrahydropyrans

Donor–acceptor cyclopropanes were engaged in a [3+3]‐annulation reaction with γ‐hydroxyenones. Sc(OTf)3 was found to be the best catalyst, and 2,4,4,5‐tetrasubstituted tetrahydropyran products were obtained in good yields under mild reaction conditions. The generality of the reaction permitted the synthesis of tetrasubstituted tetrahydropyrans bearing aryl, alkyl, and heteroaromatic groups. A catalytic asymmetric variant of this process was also studied preliminary with a chiral PyBOX ligand.

An asymmetric vinylogous Mukaiyama-Michael reaction of α,β-unsaturated 2-acyl imidazoles catalyzed by chiral Sc(iii)- or Er(iii)-pybox complexes.

A highly diastereo- and enantioselective vinylogous Mukaiyama-Michael reaction of silyloxyfurans with α,β-unsaturated 2-acyl imidazoles catalyzed by either chiral Sc(iii) or Er(iii) complexes of a pybox ligand has been reported. The enantioenriched γ-butenolides formed in the reaction were further transformed into highly functionalized γ-lactones found as important structural frameworks in a wide range of biologically active natural products.

Synthesis and characterization of metallo-supramolecular polymers from thiophene-based unimers bearing pybox ligands

A series of novel metallo-supramolecular polymers was prepared, based on 2,6-bis(2-oxazolinyl)pyridine chelating groups bridged with thiophene, bithiophene and thienothiophene as a linker, beginning from commercially available (chelidamic) acid.

Late Stage Azidation of Complex Molecules.

Selective functionalization of complex scaffolds is a promising approach to alter the pharmacological profiles of natural products and their derivatives. We report the site-selective azidation of benzylic and aliphatic C–H bonds in complex molecules catalyzed by the combination of Fe(OAc)2 and a PyBox ligand. The same system also catalyzes the trifluoromethyl azidation of olefins to form derivatives of natural products containing both fluorine atoms and azides. In general, both reactions tolerate a wide range of functional groups and occur with predictable regioselectivity. Azides obtained by functionalization of C–H and C=C bonds were converted to the corresponding amines, amides, and triazoles, thus providing a wide variety of nitrogen-containing complex molecules.