Oxazoline Ligands Research Articles

Ir–Biaryl phosphite–oxazoline catalyst libraries: a breakthrough in the asymmetric hydrogenation of challenging olefins

This work describes our progress in the successful development of phosphite/phosphinite–oxazoline ligands for the Ir-catalyzed asymmetric hydrogenation of challenging olefins.

Asymmetric catalysis with a chiral-at-osmium complex.

The first example of a chiral osmium catalyst is reported in which the overall chirality originates exclusively from a stereogenic metal center (metal-centered chirality) with all coordinating ligands being achiral. The non-C2-symmetric chiral-at-metal complex contains two cyclometalated 7-methyl-1,7-phenanthrolinium heterocycles which can be described as two chelating pyridylidene remote N-heterocyclic carbene (rNHC) ligands. The octahedral coordination sphere is completed with one CO and one acetonitrile ligand. A monodentate chiral oxazoline ligand is used as a chiral auxiliary ligand to obtain enantiomerically pure chiral-at-osmium complexes (>99 : 1 e.r.). Finally, it is demonstrated that the developed chiral-at-osmium complex is suitable for ring-closing enantioselective C(sp3)-H aminations, including the first example of catalytic enantioselective cyclizations of azidoformates to chiral 2-oxazolidinones.

Chiral Bis(oxazoline) Ligands as C2-Symmetric Chiral Auxiliaries for the Synthesis of Enantiomerically Pure Bis-Cyclometalated Rhodium(III) Complexes

The synthesis of enantiomerically pure bis-cyclometalated rhodium(III) complexes using chiral bis(oxazoline) ligands as C2-symmetric chiral auxiliaries is described. Bis(oxazolines) are versatile chiral ligands for asymmetric catalysis but have not been applied to the resolution of racemic mixtures of transition-metal complexes. Due to their C2 symmetry, chiral bis(oxazolines) are particularly useful for the synthesis of nonracemic transition-metal complexes with lower symmetry, and this is demonstrated with the synthesis of an enantiomerically pure rhodium(III) complex containing two different cyclometalated ligands.

Mechanistic Investigation of Enantioconvergent Kumada Reactions of Racemic α-Bromoketones Catalyzed by a Nickel/Bis(oxazoline) Complex.

In recent years, a wide array of methods for achieving nickel-catalyzed substitution reactions of alkyl electrophiles by organometallic nucleophiles, including enantioconvergent processes, have been described; however, experiment-focused mechanistic studies of such couplings have been comparatively scarce. The most detailed mechanistic investigations to date have examined catalysts that bear tridentate ligands and, with one exception, processes that are not enantioselective; studies of catalysts based on bidentate ligands could be anticipated to be more challenging, due to difficulty in isolating proposed intermediates as a result of instability arising from coordinative unsaturation. In this investigation, we explore the mechanism of enantioconvergent Kumada reactions of racemic α-bromoketones catalyzed by a nickel complex that bears a bidentate chiral bis(oxazoline) ligand. Utilizing an array of mechanistic tools (including isolation and reactivity studies of three of the four proposed nickel-containing intermediates, as well as interrogation via EPR spectroscopy, UV-vis spectroscopy, radical probes, and DFT calculations), we provide support for a pathway in which carbon-carbon bond formation proceeds via a radical-chain process wherein a nickel(I) complex serves as the chain-carrying radical and an organonickel(II) complex is the predominant resting state of the catalyst. Computations indicate that the coupling of this organonickel(II) complex with an organic radical is the stereochemistry-determining step of the reaction.

Chiral Cyclometalated Oxazoline Gold(III) Complex-Catalyzed Asymmetric Carboalkoxylation of Alkynes

Asymmetric catalysis by using novel chiral O,O'-chelated 4,4'-biphenol cyclometalated oxazoline gold(III) complexes has been developed. A high yield (≤89%) and a high enantioselectivity (≤90% ee) were achieved in asymmetric carboalkoxylation of alkynes. Enantioselectivity could be significantly improved from 19% to 90% ee by increasing the steric size of the substituent on the chiral oxazoline ligand. Catalytically active AuIII species and the origin of chiral induction are proposed.

Palladium-Catalyzed Amide-Directed Enantioselective Carboboration of Unactivated Alkenes Using a Chiral Monodentate Oxazoline Ligand

A Pd-catalyzed carboxamide-directed enantioselective 1,2-carboboration reaction of unactivated alkenes with C–H nucleophiles and B2Pin2 has been developed using a second generation of chiral monode...

PdII/Novel Chiral Cinchona Alkaloid Oxazoline‐Catalyzed Enantioselective Oxidative Cyclization of Aromatic Alkenyl Amides

A highly enantioselective PdII‐catalyzed aza‐Wacker oxidation tandem cyclization of aromatic nitrogen‐containing dienes has been achieved in the presence of novel chiral cinchona alkaloid oxazoline ligands for the first time, affording chiral dihydroindole nitrogen‐containing polycyclic compounds with good yields (up to 83 %), high diastereoselectivities (> 95:5 dr), and excellent enantioselectivities (up to 97 % ee).

Spiro indane-based phosphine–oxazoline ligands for palladium-catalyzed asymmetric arylation of cyclic N-sulfonyl imines

Palladium complexes of indane-based phosphine–oxazoline ligands with a spirocarbon stereogenic center were examined for asymmetric addition of arylboronic acids to cyclic N-sulfonyl imines. Excellent reaction activities (up to 99% yield) and enantioselectivities (up to 99% ee) were obtained with a broad scope of substrate.

Synthesis of Tridentate Chiral Spiro Aminophosphine−Oxazoline Ligands and Application to Asymmetric Hydrogenation of α‐Keto Amides

AbstractA new type of tridentate chiral spiro aminophosphine−oxazoline ligands (SpiroOAP) have been synthesized through four steps. The SpiroOAP ligands are highly efficient for the asymmetric hydrogenation of α‐keto amides, providing a variety of synthetically useful α‐hydroxy amides with excellent enantioselectivity (up to 98% ee) and turnover numbers (up to 10,000).magnified image

Cobalt-Catalyzed Asymmetric Hydrogenation of Vinylsilanes with a Phosphine–Pyridine–Oxazoline Ligand: Synthesis of Optically Active Organosilanes and Silacycles

The asymmetric hydrogenation of vinylsilanes catalyzed by a new C1-symmetric phosphine–pyridine–oxazoline cobalt complex is described. The method provides an efficient approach to chiral tertiary s...

Asymmetric construction of atropisomeric biaryls via a redox neutral cross-coupling strategy

Atropisomerically enriched biaryl frameworks are ubiquitous in many fields of chemistry. Enantioselective aryl–aryl cross-coupling provides the most straightforward entry to atropisomeric biaryls, with remarkable application potential in the field of chemical science. However, their development is hindered due to the lack of convenient and pragmatic protocols. Here, we report a method for the asymmetric synthesis of a myriad of 2-amino-2′-hydroxy-1,1′-binaphthyl (NOBIN) and 1,1’-binaphthyl-2,2’-diamine (BINAM) derivatives in excellent yields and enantioselectivities via a redox-neutral cross-coupling protocol. Two complementary systems were devised employing a chiral phosphoric acid–salt complex or Ni(OTf)2/chiral bis(oxazoline) ligand catalytic system for accessing atropisomeric NOBIN and BINAM derivatives, respectively. This work provides an alternative avenue to enantioenriched biaryls, and provides the capability to explore the synthetic and catalytic potentials of NOBIN- and BINAM-based frameworks. Axially chiral biaryls have proven to have a wide variety of uses—perhaps most importantly as ligands in asymmetric catalysis—but their synthesis remains challenging. Here, Bin Tan and colleagues report a redox-neutral aryl–aryl coupling, providing a direct route to N,N and N,O axially chiral biaryls in high yields and enantioselectivities.

Directed, Palladium(II)-Catalyzed Enantioselective anti-Carboboration of Alkenyl Carbonyl Compounds

A substrate-directed enantioselective anti-carboboration reaction of alkenes has been developed, wherein a carbon-based nucleophile and a boron moiety are installed across the C=C bond through a 5-membered palladacycle intermediate. A preliminary result also shows it is possible to extend this reaction to alkenes that are more distal from the directing group and react via a 6-membered palladacycle. The reaction is promoted by a palladium(II) catalyst and a monodentate oxazoline ligand. A range of enantioenriched secondary alkylboronate products were obtained with moderate to high enantioselectivity that could be further upgraded by recrystallization. This work represents an efficient method to synthesize versatile and valuable alkylboronate building blocks. Building on an earlier mechanistic proposal by Peng, He, and Chen, a revised model is proposed to account for the stereoconvergent nature of this transformation.

Desymmetrization by Asymmetric Copper-Catalyzed Intramolecular C-H Insertion Reactions of α-Diazo-β-oxosulfones.

Effective desymmetrization in copper-catalyzed intramolecular C-H insertion reactions of α-diazo-β-oxosulfones in the formation of fused thiopyran dioxides is described for the first time. The use of a copper-bis(oxazoline)-NaBARF catalyst complex system leads to formation of the major thiopyran dioxide stereoisomer with up to 98:2 dr and up to 98% ee. The effect of varying the bis(oxazoline) ligand, copper salt, and site of C-H insertion on both diastereo- and enantioselectivities of these intramolecular C-H insertion reactions has been investigated. Similarly, desymmetrization in the formation of a fused cyclopentanone proceeds with up to 64% ee. These results represent the highest enantioselectivity reported to date in a copper-mediated desymmetrization through C-H insertion.

Palladium‐Catalyzed Asymmetric Dihydroxylation of 1,3‐Dienes with Catechols

Summary of main observation and conclusionA palladium‐catalyzed asymmetric dihydroxylation of 1,3‐dienes with catechols is developed using chiral pyridinebis(oxazoline) ligands. Various chiral 2‐substituted 1,4‐benzodioxanes could be synthesized with moderate to high yields and enantioselectivities from readily available starting materials. The reaction is proposed to proceed through a cascade Wacker‐type hydroxypalladation/asymmetric allylation process.

Scalable Synthesis of N‐Acetylated α‐Amino Acid‐Derived Oxazoline Ligands

A scalable cost‐effective synthesis of promising α‐amino acid‐derived oxazoline ligands has been developed. The advantage of the reported procedures is the use of crystallization for the purification of key intermediates and final products. The ligands obtained have recently demonstrated remarkable enantioselectivity in Pd (II) catalyzed C─H activation reactions. Hence, more rational synthetic route presented here will contribute to this rapidly growing field of chemistry.

An autonomous self-optimizing flow machine for the synthesis of pyridine–oxazoline (PyOX) ligands

A continuous flow synthesis of PyOX ligands has been developed using an autonomous self-optimizing flow reactor.

Catalyst-Controlled Regioselective Acylation of β-Ketoesters with α-Diazo Ketones Induced by Visible Light.

A catalyst-controlled acylation reaction of β-ketoesters was developed for the first time by combining visible-light photoactivation with Lewis acid or base catalysis. By employing a NiCl2·glyme complex with a bis(oxazoline) ligand as the Lewis acid catalyst, C-acylation products are exclusively achieved, while utilizing pyridine or DABCO as the Lewis base catalyst affords O-acylation products with complete regioselectivity. A range of β-ketoesters with satisfactory structural diversity were suitable for this transformation, demonstrating the functional group compatibility of the method, which was attributed to the mild reaction conditions. This success is heavily built upon the visible-light-induced Wolff rearrangement and the unique catalytic activation modes, and thus, this work significantly expands the applications of ketene chemistry.

Iron-Catalyzed Suzuki–Miyaura Cross-Coupling Reactions between Alkyl Halides and Unactivated Arylboronic Esters

An iron-catalyzed cross-coupling reaction between alkyl halides and arylboronic esters was developed that does not involve activation of the boronic ester with alkyllithium reagents nor requires magnesium additives. A combination of experimental and theoretical investigations revealed that lithium amide bases coupled with iron complexes containing deprotonated cyanobis(oxazoline) ligands were best to obtain high yields (up to 89%) in catalytic cross-coupling reactions. Mechanistic investigations implicate carbon-centered radical intermediates and highlight the critical importance of avoiding conditions that lead to iron aggregates. The new iron-catalyzed Suzuki-Miyaura reaction was applied toward the shortest reported synthesis of the pharmaceutical Cinacalcet.

Development of Novel Chloramphenicol Scaffold‐Based Chiral Hydroxyl Oxazoline Ligands and Their Application to the Asymmetric Alkynylation of Isatins

AbstractThe synthesis of new chloramphenicol base‐derived chiral hydroxyl oxazoline ligands, and their use in the first Zn(OTf)2‐catalyzed enantioselective alkynylation of isatins are described. This transformation features mild reaction conditions, a remarkably broad substrate scope, and excellent functional group tolerance, affording the corresponding tertiary propargylic alcohols in high yields and with high enantioselectivities. The application of chiral hydroxyl oxazolines as ligands in Zn(II)‐catalyzed asymmetric alkynylation reactions is unprecedented.magnified image

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.