Oxazoline Ligands Research Articles

Asymmetric copper-catalyzed Diels–Alder reaction revisited: control of the structure of bis(oxazoline) ligands

Synthesis of 1,4-bis(oxazoline) ligands bearing a bicyclo[2,2,2]backbone derived from 9,10-dihydro-9,10-ethanoanthacene trans-dicarboxylic acid was revisited. Starting from l- or d-amino alcohols and either (S,S) or (R,R)-dihydroethano trans-dicarboxylic acid, a complete series of ligands was evaluated in the copper-catalyzed Diels–Alder reaction. The most efficient ligands with a phenyl substituent on the oxazoline ring afforded enantiomeric excess up to 98%. This is different from previous results indicating that the best enantioselectivity involved a diastereomeric ligand with the meso-backbone.

Chiral oxazoline ligands containing a 1,2,4-triazine ring and their application in the Cu-catalyzed asymmetric Henry reaction

Eleven members of new ligand class incorporating a chiral oxazoline and a 1,2,4-triazine ring have been synthesized via Pd-catalyzed amination reaction of 3-halo-1,2,4-triazines with 2-(o-aminophenyl)oxazolines. Buchwald–Hartwig amination of 3-halo-1,2,4-triazines was investigated to establish the best conditions for synthesis of the title ligands. Catalytic activity of the new ligands was evaluated in the asymmetric Henry reaction of nitromethane with a variety of aromatic and aliphatic aldehydes. The β-hydroxy nitroalkanes were obtained in high yields (up to 95%), and moderate-to-good enantioselectivity (up to 82% ee).

Carbenoid insertions into benzylic C–H bonds with heterogeneous copper catalysts

The copper complexes with bis(oxazoline) or azabis(oxazoline) ligands, once supported on laponite clay by electrostatic interactions, are able to catalyze the insertion of carbenoids in benzylic C–H bonds. In contrast with rhodium catalysts, they are more active with tertiary than with secondary bonds, through a similar mechanism as shown by Hammet correlation. Enantioselectivities are only moderate, with values up to 50% ee. The immobilized catalysts are partially recoverable and the best results are obtained in the case of reactions with high chemoselectivity.

DFT Study of a 5‐endo‐trig‐Type Cyclization of 3‐Alkenoic Acids by Using Pd–Spiro‐bis(isoxazoline) as Catalyst: Importance of the Rigid Spiro Framework for Both Selectivity and Reactivity

The reaction pathway of an enantioselective 5-endo-trig-type cyclization of 3-alkenoic acids catalyzed by a chiral palladium-spiro-bis(isoxazoline) complex, Pd-SPRIX, has been studied by density functional theory calculations. The most plausible pathway involves intramolecular nucleophilic attack of the carboxylate moiety on the C=C double bond activated by Pd-SPRIX and β-H elimination from the resulting organopalladium intermediate. The enantioselectivity was determined in the cyclization step through the formation of a π-olefin complex, in which one of the two enantiofaces of the olefin moiety was selected. The β-H elimination occurs via a seven-membered cyclic structure in which the acetate ligand plays a key role in lowering the activation barrier of the transition state. In the elimination step, the SPRIX ligand was found to behave as a monodentate ligand due to the hemilability of one of the isoxazoline units thereby facilitating the elimination. Natural population analysis of this pathway showed that the more weakly electron-donating SPRIX ligand, compared with the bis(oxazoline) ligand, BOX, facilitated the formation of the π-olefin complex intermediate, leading to a smaller overall activation energy and a higher reactivity of the Pd-SPRIX catalyst.

π-Stacking interactions at the service of [Cu]-bis(oxazoline) recycling

Anthracene- and pyrene-tagged bis(oxazoline) ligands have been prepared and immobilized on charcoal, fullerene, and single-walled carbon nanotubes through π–π interactions. The corresponding copper complexes have been evaluated for their propensity to promote heterogeneous asymmetric Henry and ene reactions. The best results, in terms of activity, selectivity, and stability toward the recycling procedure have been obtained with the pyrene/SWCNT system, as the first example demonstrating the usefulness of such reversible interactions for the asymmetric formation of new C–C bonds.

Expanded Scope of the Asymmetric Hydrogenation of Minimally Functionalized Olefins Catalyzed by Iridium Complexes with Phosphite–Thiazoline Ligands

AbstractWe have replaced the oxazoline group with a thiazoline moiety in one of the most successful of the phosphite–oxazoline ligand families for the Ir‐catalyzed hydrogenation of minimally functionalized olefins. A small but structurally important library of Ir phosphite–thiazoline precatalysts (Ir‐L1–L2 a–e) has been developed by changing the substituents/configurations at the biaryl phosphite group. We found that the replacement of the oxazoline with a thiazoline moiety in the ligand design is beneficial in terms of substrate scope.

Simple and cheap steric and electronic characterization of the reactivity of Ru(II) complexes containing oxazoline ligands as epoxidation catalysts

The reactivity of a new family of complexes with general formula [RuIV(T)(R-D)(O)]2+ (T=trispyrazolylmethane (tpm); D=N-(1-hydroxy-3-methylbutan-(2S)-(−)-2-yl)-(4S)-(−)-4-isopropyl-4,5-dihydrooxazole-2-carbimidate, R=Bz (1); iPr (2)) has been analyzed. There is a significant difference in regioselectivity between the two catalysts in the epoxidation of 4-vinylcyclohexene; 1 leads to the regioselective oxidation at the ring alkene position, whereas 2 leads to the oxidation at the terminal position. Although computational calculations indicate small energy differences, both the geometry through steric maps and the electronic parameters of the reactants via conceptual DFT, or charges via NPA, explain the reactivity differences found for the catalysts depending on the substituents of the oxazoline ligands.

Chemoselective Oxidation of Polyols with Chiral Palladium Catalysts

Chiral palladium-based catalysts derived from pyridinyl oxazoline (pyOx) ligands catalyze the oxidation of alcohols, including 1,2-diols, triols, and tetraols, with high regio- and chemoselectivity. Screening of various chiral oxazoline-derived ligands for the oxidation of a model diol, 1,2-propanediol (1,2-PD), revealed that the nature of the ligand had a significant influence on the activity and chemoselectivity for oxidation of vicinal diols. The PyOx ligands containing an α-methyl substituent were the most active for the oxidation of 1,2-PD using benzoquinone as the terminal oxidant. Oxidation of vicinal diols and polyols occurs selectively at the secondary alcohol to afford α-hydroxy ketones in isolated yields of 62–87%. Chemoselective oxidation of meso-erythritol with the chiral [(S)-(α-Me(tert-Bu)PyOx)Pd(OAc)]2[OTf]2 afforded (S)-erthyrulose in 62% yield and 24% ee.

Chiral Octahedral Phosphano–Oxazoline Iridium(III) Complexes as Catalysts in Asymmetric Cycloaddition Reactions

The synthesis and characterization of cationic iridium(III) aqua complexes of the formula [IrH(H2O)(PN*)(PP)][SbF6]2 (PN* = chiral phosphano–oxazoline ligand; PP = diphosphane) as well as that of the OPOF2-containing complex [IrH(OPOF2)(PNiPr)(dppp)][SbF6] (10) are reported. The X-ray molecular structures of [IrH(H2O)(PNInd)(dppe)][SbF6]2 (1), [IrH(H2O)(PNInd)(dppen)][SbF6]2 (2), and 10a have been determined. Dichloromethane solutions of these aqua complexes efficiently catalyze the enantioselective 1,3-dipolar cycloaddition of the nitrone N-benzylidenephenylamine N-oxide to methacrolein and Diels–Alder reactions between cyclopentadiene and trans-β-nitrostyrenes. In the first case, the catalytic reaction occurs with excellent endo selectivity and ee up to 85%; the Diels–Alder reaction occurs rapidly at room temperature with good endo:exo selectivity and ee up to 90%. The dipolar cycloaddition intermediates [IrH(methacrolein)(PNInd)(PP)][SbF6]2 (PP = (S,S)-chiraphos (11), (R)-prophos (12)) have been charac...

Diastereoselective Synthesis of Chiral Octahedral Iridium(III) Phosphano–Oxazoline Complexes

Reaction of the dimer [Ir(μ-Cl)(η2-coe)2]2 (coe = cyclooctene) with chiral phosphano–oxazoline ligands (PN*) renders neutral mononuclear iridium(I) complexes of the formula [IrCl(η2-coe)(PN*)] (1, 2), which in turn are oxidized to the corresponding iridium(III) hydride species [IrCl2H(η2-coe)(PN*)] (3, 4) by treatment with aqueous HCl. The latter react with diphosphanes (PP) in the presence of NaSbF6 to afford cationic complexes of stoichiometry [IrClH(PN*)(PP)][SbF6] (5–16). The fluorophenyldiphosphane-containing compounds [IrClH(PN*)(dfppe)][SbF6] (15, 16) evolve to the corresponding Ir(I) species [Ir(PN*)(dfppe)][SbF6] (17, 18) by HCl loss. The new compounds have been fully characterized by analytical and spectroscopic means, including the molecular structure determination of [IrCl2H(η2-coe)(PNInd)] (3), [IrClH(PNInd)(dppen)][SbF6] (6a,b), [IrClH(PNInd)(dppp)][SbF6] (7a), [IrClH(PNiPr)(dppp)][SbF6] (13a), [IrClH(PNInd)(dfppe)][SbF6] (15), [Ir(PNInd)(dfppe)][SbF6] (17), and [Ir(PNiPr)(dfppe)][SbF6] (18)...

ChemInform Abstract: Palladium(II)‐Catalyzed Enantioselective Arylation of α‐Imino Esters.

AbstractIt is found that Pd(OAc)2 in combination with the oxazoline ligand BOX efficiently promote the asymmetric coupling of α‐imino esters with a number of arylboronic acids yielding arylglycine esters in good to high enantioselectivity.

Copper(II)-Catalyzed Enantioselective Fluorination of β-Keto Esters Using Chiral Spiro Oxazoline Ligands

Highly enantioselective fluorination of α-alkyl-β-keto esters was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)2 and chiral spiro oxazoline ligands. The fluorination proceeded in a highly enantioselective manner both when cyclic and acyclic substrates were applied to the reaction. Fluorination of α-alkyl­malonates was also performed to afford the corresponding products in good enantioselectivity.

Asymmetric benzoylation of hydrobenzoin by copper(ii) bis(oxazoline) anchored onto ordered mesoporous silicas and their carbon replicas

A copper(II) complex with a commercial chiral bis(oxazoline) was anchored onto ordered mesoporous silica materials and their respective carbon replicas. The amount of transition metal complex loaded onto the mesostructured solids was determined by ICP-AES and the materials were also characterized by elemental analysis, FTIR, TG/DSC and isotherms of N2 adsorption at −196 °C. For the first time the asymmetric benzoylation of a 1,2-diol was performed in the heterogeneous phase by using an anchored commercial bis(oxazoline) ligand. The effect of the type of mesoporous material on the catalytic parameters, as well as on the reutilization of catalysts in several catalytic cycles, was checked. All the composites prepared were active, selective and enantioselective in this asymmetric organic transformation. Using the two ordered mesoporous silicas as supports good selectivities, with comparable yields and TONs to the homogeneous phase reaction, were obtained. Furthermore these two heterogeneous catalysts are more stable upon reuse than the corresponding ordered carbon replica materials. One of the former heterogeneous catalysts, with mesoporous silica as a support, could be further reused for 4 consecutive cycles without significant loss of selectivity, the TON or enantioselectivity.

New Application Progress of Chiral Bis(oxazoline) Ligands in Asymmetric Catalysis

The recent progress of bis(oxazoline) ligands applications in asymmetric catalysis is reviewed, in particular the

Enantio- and diastereoselective palladium catalysed arylative and vinylative allene carbocyclisation cascades

The enantioselective synthesis of heavily decorated spirolactams has been accomplished via an arylative or vinylative allene carbocyclisation cascade. Mediated by silver phosphate, a range of allene-linked pro-nucleophiles and aryl or vinyl iodides were reacted in the presence of catalytic Pd(OAc)2 and chiral bis(oxazoline) ligands to afford the spirolactam products in good yields and high enantio- and diastereoselectivities.

Aromatic C–H coupling with hindered arylboronic acids by Pd/Fe dual catalysts

An aerobic oxidative coupling of arenes/alkenes with arylboronic acids (C–H/C–B coupling) using catalytic Pd(II)–sulfoxide–oxazoline (sox) ligand and iron–phthalocyanine (FePc) has been developed. This dual catalyst system enables the synthesis of sterically hindered heterobiaryls and styrene derivatives under air without stoichiometric co-oxidants. Additionally, this chemistry demonstrated an advance toward an enantioselective biaryl coupling through C–H functionalization.

Catalytic Epoxidations with Pyridinebis(oxazoline)–Methyltrioxorhenium Complexes and Nitrogen‐Containing Catalyst Systems

The epoxidation of olefins with methyltrioxorhenium (MTO) in the presence of various chiral oxazolines and pyridinebis(oxazoline) ligands as well as achiral N-ligands has been investigated. By applying 1-octene as a model system, reaction conditions were optimized, and high yields and good chemoselectivity (>90 %) were achieved. By applying other aromatic and aliphatic olefins, similar chemoselectivities and up to 19 % enantioselectivity were obtained.

ChemInform Abstract: The Synthesis of Phosphine Oxide‐Linked Bis(oxazoline) Ligands and Their Application in Asymmetric Allylic Alkylation.

Abstract The phosphine oxide-linked bis(oxazoline) ligands were designed and synthesized in two ways. One is the coupling of Grignard reagent derived from 2-(2-bromophenyl)oxazoline with phenylphosphonic dichloride, another route is the condensation of bis(2-formylphenyl)(phenyl)phosphine oxide with chiral amino alcohols followed by NBS oxidation. These new bis(oxazoline) ligands were applied in Pd-catalyzed asymmetric allylic alkylation reactions and good yields and enantioselectivities were obtained with diphenyl substituted ligand (up to 95% ee).

Enantioselective Cyclopropanation of Indoles: Construction of All-Carbon Quaternary Stereocenters

The first enantioselective copper-catalyzed cyclopropanation of N-acyl indoles is described. Using carbohydrate-based bis(oxazoline) ligands (glucoBox), the products were obtained in up to 72% ee. Cyclopropanation of N-Boc 3-methyl indole yielded a product with an all-carbon quaternary stereocenter, which is a valuable building block for the synthesis of indole alkaloids: Deprotection and rearrangement gave a tricyclic hemiaminal ester in 96% ee, which was subsequently employed as a key intermediate for the synthesis of (-)-desoxyeseroline.

ChemInform Abstract: Highly Enantioselective Asymmetric Hydrogenation of (E)‐β,β‐Disubstituted α,β‐Unsaturated Weinreb Amides Catalyzed by Ir(I) Complexes of SpinPhox Ligands.

The Ir(I) complexes of chiral spiro phosphino–oxazoline ligands (SpinPhox) have demonstrated good to excellent enantioselectivity in the asymmetric hydrogenation (AH) of a variety of (E)-β,β-disubstituted α,β-unsaturated N-methoxy-N-methylamides, affording the corresponding optically active Weinreb amides with up to 97% ee.