Oxazoline Ligands Research Articles

A study of chiral oxazoline ligands with a 1,2,4-triazine and other six-membered aza-heteroaromatic rings and their application in Cu-catalysed asymmetric nitroaldol reactions

Enantiomerically pure oxazoline ligands with variously substituted 1,2,4-triazine rings have been synthesized using the Pd-catalysed cross-coupling amination of 3-halo-1,2,4-triazines. The catalytic efficiency of the ligands was studied in the asymmetric Henry reaction of nitromethane with several aldehydes. The appropriate β-nitro alcohols were formed in good yields (up to 93%) and with up to 78% ee. The impact of the substitution of the 1,2,4-triazine ring on the nitroaldol reaction is discussed. In order to investigate the influence of the 1,2,4-triazine ring on the catalytic activity of the ligands, ligands where the 1,2,4-triazine ring was replaced by a pyridine, pyrimidine, pyrazine or pyridine N-oxide ring were synthesized and applied to asymmetric nitroaldol reactions.

Chiral Palladium(II) and Nickel(II) Complexes with C2-Symmetrical Tridentate Bis(oxazoline) Ligands: Synthesis, Characterization, and Catalytic Norbornene Polymerization

A series of chiral palladium(II) and nickel(II) complexes bearing a C2-symmetric monoanionic tridentate bis(oxazoline) ligand, (R2-(S,S)-BOZ)M(X) (1–6: R = CH(CH3)2, M = Pd, X = OAc (1); R = CH(CH3)2, M = Pd, X = Cl (2); R = Ph, M = Pd, X = Cl (3); R = Ph, M = Ni, X = Cl (4); R = CH(CH3)2, M = Ni, X = Cl (5); R = CH(CH3)2, M = Pd, X = OTf (6)), have been synthesized and structurally characterized. The experimental results demonstrate that such chiral palladium(II) and nickel(II) complexes bearing C2-symmetric tridentate ligands in which the monoanionic group is located inside are effective for norbornene polymerization. In the presence of various cocatalysts such as MAO, MMAO, and activator/AlR3, these chiral palladium(II) complexes exhibit much higher activities of up to 4.8 × 108 g of PNB (mol of Pd)−1 h–1 for the vinylic polymerization of norbornene, affording insoluble polynorbornenes with high packing density. In contrast, the chiral nickel(II) complexes show relatively low activities of ca. 4.5 × 107 g of PNB (mol of Ni)−1 h–1 and produce both insoluble polynorbornenes and soluble high-molecular-weight polynorbornenes with moderate molecular weight distributions.

Electrostatic immobilization of bis(oxazoline)-copper complexes on mesoporous crystalline materials: Cation exchange vs. incipient wetness methods

Chiral copper complexes with bis(oxazoline) and azabis(oxazoline) ligands have been immobilized by non-covalent interactions on mesoporous materials. The presence of negative charges achieved by the isomorphous substitution of silicon by aluminium is required to retain the complexes on the support. Cation-exchange was found to be not as efficient as observed with layered clays, and produce catalysts which lose their chiral ligand and give low enantioselectivity. A method employing incipient wetness produces more stable catalysts, whose activity varies to some extent according to the structure of the mesoporous material on which it is supported, and the nature of the chiral ligand.

Epoxidation of alkenes and oxidation of sulfides catalyzed by a new binuclear vanadium bis-oxazoline complex

Bis(oxazoline) ligand, [2,2′-(1,3-phenylene)bis(oxazole-4,2-diyl)]-dimethanol, derived from dicyanobenzene was applied as ligand for complexation with vanadium. The catalyst was characterized by FT-IR, UV–Vis, 1H NMR spectroscopic methods, CHNS, ICP and thermal analyses, and magnetic susceptibility. The catalytic activity of this complex was then studied in the epoxidation of alkenes with TBHP (tert-butyl hydroperoxide), in acetonitrile. The effect of reaction parameters such as kind of solvent and oxygen donors was studied in the epoxidation of cyclooctene. The catalytic activity of this catalyst was also investigated in the oxidation of sulfides with H2O2 in ethanol and the corresponding sulfoxides and sulfones were produced.

A novel iron complex containing an N,O-type bidentate oxazoline ligand: Synthesis, X-ray studies, DFT calculations and catalytic activity

A five-coordinated Fe(III) complex with the distorted trigonal bipyramidal configuration was synthesized by reactions of FeCl3⋅6H2O and 2-(2′-hydroxyphenyl)oxazoline (Hphox) as a bidentate ON donor oxazoline ligand. Complex [Fe(phox)2Cl] was fully characterized, including by single-crystal X-ray structure analysis. DFT calculations were accompanied with experimental results in order to obtain a deeper insight into the electronic structure and vibrational normal modes of complex. Oxidation of sulfides to sulfoxides in one-step was conducted by this complex as catalyst using urea hydrogen peroxide (UHP) in mixture of CH2Cl2/CH3OH (1:1) under air at room temperature. The results show that using this system in oxidation of sulfides, sulfoxides are obtained as the main products, together with variable amounts of sulfones (⩽13%), depending on the nature of the substrate.

ChemInform Abstract: Electronic Effects of Aryl‐Substituted Bis(oxazoline) Ligands on the Outcome of Asymmetric Copper‐Catalyzed C—H Insertion and Aromatic Addition Reactions.

ChemInform Abstract: Electronic Effects of Aryl‐Substituted Bis(oxazoline) Ligands on the Outcome of Asymmetric Copper‐Catalyzed C—H Insertion and Aromatic Addition Reactions.

ChemInform Abstract: A Computational Mechanistic Study of an Unprecedented Heck‐Type Relay Reaction: Insight into the Origins of Regio‐ and Enantioselectivities.

Density functional theory (DFT) calculations (B3LYP and M06) have been utilized to study a newly reported Heck-type reaction that uses an allylic or alkenyl alcohol as substrate and palladium as catalyst in the form of a chelate with a chiral pyridine oxazoline (PyrOx) ligand. The reaction not only controls the regio- and enantioselectivities of arylation of the C═C bond, but also forms the carbonyl functionality up to four bonds away from the aryl substituent via tandem C═C bond migration and enol-to-keto conversion. Computations performed on representative reaction systems allow us to propose a detailed mechanism with several key steps. Initial oxidation of palladium(0) by aryldiazonium generates active arylpalladium(II) species that bind the C═C bond of an allylic or alkenyl alcohol. The activated C═C bond inserts into the palladium-aryl moiety to attain aryl substitution and a chiral carbon center, and the resulting complex undergoes β-hydride elimination to give a new C═C bond that can repeat the insertion/elimination process to move down the carbon chain to form an enol that tautomerizes to a highly stable carbonyl final product. The calculations reveal that the C═C bond migratory insertion step determines both the regioselectivity and the enantioselectivity of arylation, with the former arising mainly from the electronic effect of the hydroxyl group on the charge distribution over the C═C bond and the latter originating from a combination of steric repulsion, trans influence, and C-H/π dispersion interactions.

Recent Applications of C 1-Symmetric Bis(oxazoline)-Containing Ligands in Asymmetric Catalysis

Bis(oxazolines) are a well-known class of ligands in the area of asymmetric catalysis. Most of these ligands are C 2-symmetric due to the synthetic route employed for their synthesis. This review article summarizes the recent progress of the closely related, but relatively unexplored, C 1-symmetric bis(oxazoline) ligands and compares and contrasts the two where applicable. 1 Introduction 2 Bis(oxazolines) 2.1 Bis(oxazolines) with Differentially Substituted Oxazolines 2.2 Bis(oxazolines) with Asymmetrically Substituted Linking Unit 2.3 Bis(oxazolines) with Differentially Substituted Oxazolines and Asymmetrically Substituted Linking Unit 3 Conclusion

New Chiral Palladacycles from an Unprecedented Cyclopalladation of Cyclobutadiene-Bound Phenyl Groups of Cobalt Sandwich Compounds

Reaction of in situ generated {η5-[MeOC(O)]C5H4}Co(PPh3)2 with methyl 3-phenyl-2-propynoate followed by diphenylacetylene in refluxing toluene resulted in the formation of the cobalt sandwich compound {η5-[MeOC(O)]C5H4}Co{η4-C4Ph3[C(O)OMe]} (1), having methyl ester units on both the cyclopentadienyl (Cp) and cyclobutadiene (Cb) rings. Hydrolysis of the ester groups using aqueous KOH resulted in the dicarboxylic acid {η5-C5H4[C(O)OH]}Co{η4-C4Ph3[C(O)OH]} (2). The dicarboxylic acid 2 was converted to the novel bis(oxazolinyl) derivative [η5-(4-iPr-2-Ox)C5H4]Co[η4-C4Ph3(4-iPr-2-Ox)] (3; Ox = oxazolinyl) by its reaction with oxalyl chloride, (S)-2-amino-3-methyl-1-butanol, triethylamine, and mesyl chloride. Reaction of the chiral bis(oxazoline) ligand 3 with Pd(OAc)2 in acetic acid at 60 °C resulted in the formation of the novel chiral palladacycle 4, resulting from an unprecedented cyclopalladation involving one of the cyclobutadiene-bound phenyl groups. Palladacycle 4 has two trans-oriented oxazolinyl units...

Oxidation of alkenes and sulfides catalyzed by a new binuclear molybdenum bis-oxazoline complex

A novel bis(oxazoline) ligand derived from 1,3-dicyanobenzene was prepared and applied as a ligand for the preparation of a new binuclear molybdenyl complex. This ligand was characterized by UV–Vis, mass, 1H NMR, and FT-IR spectroscopic methods, thermal and elemental analysis and X-ray diffraction. The molybdenum complex was prepared by the reaction of this ligand with MoO2(acac)2. The catalyst was also characterized by FT-IR, UV–Vis, and ICP spectroscopy, elemental and thermal analysis. This catalytic system was efficiently used for the oxidation of alkenes and sulfides in the presence of TBHP. The effect of different solvents and kind of oxygen donor was also studied in the oxidation reactions.

A Computational Mechanistic Study of an Unprecedented Heck-Type Relay Reaction: Insight into the Origins of Regio- and Enantioselectivities

Density functional theory (DFT) calculations (B3LYP and M06) have been utilized to study a newly reported Heck-type reaction that uses an allylic or alkenyl alcohol as substrate and palladium as catalyst in the form of a chelate with a chiral pyridine oxazoline (PyrOx) ligand. The reaction not only controls the regio- and enantioselectivities of arylation of the C═C bond, but also forms the carbonyl functionality up to four bonds away from the aryl substituent via tandem C═C bond migration and enol-to-keto conversion. Computations performed on representative reaction systems allow us to propose a detailed mechanism with several key steps. Initial oxidation of palladium(0) by aryldiazonium generates active arylpalladium(II) species that bind the C═C bond of an allylic or alkenyl alcohol. The activated C═C bond inserts into the palladium-aryl moiety to attain aryl substitution and a chiral carbon center, and the resulting complex undergoes β-hydride elimination to give a new C═C bond that can repeat the insertion/elimination process to move down the carbon chain to form an enol that tautomerizes to a highly stable carbonyl final product. The calculations reveal that the C═C bond migratory insertion step determines both the regioselectivity and the enantioselectivity of arylation, with the former arising mainly from the electronic effect of the hydroxyl group on the charge distribution over the C═C bond and the latter originating from a combination of steric repulsion, trans influence, and C-H/π dispersion interactions.

N-Heterocyclic carbene (NHC) palladium(II) complexes bearing chiral oxazoline ligands and their catalytic activities in allylic alkylation reactions

NHC--Pd(II) complexes bearing a chiral oxazoline ligand (IIIa--f) were synthesized by cleavage of dimeric palladium complexes with the oxazoline ligand. They were fully characterized by 1H and 13C NMR and elemental analyses. The catalytic activity of the complexes (IIIa--f) in allylic alkylation reactions was evaluated. The complex IIIa was found to be the most active catalyst. Very low ee values indicate that the oxazoline is dissociated from the active catalytic species.

Bis(oxazoline)-copper catalyzed enantioselective hydrophosphonylation of aldehydes

A highly enantioselective copper-catalyzed hydrophosphonylation of aldehydes in the presence of bis(oxazoline) ligand is presented.

Asymmetric cobalt catalysts for hydroboration of 1,1-disubstituted alkenes

Chiral iminopyridine oxazoline (IPO) ligands were designed, synthesized and utilized for the first cobalt-catalyzed highly regio- and enantioselective anti-Markovnikov hydroboration of 1,1-disubstituted aryl alkenes. These novel IPO ligands will likely be of high value for asymmetric transformations with first-row transition metals.

Asymmetric benzoylation and Henry reaction using reusable polytopic bis(oxazoline) ligands and copper(ii)

Multitopic bis(oxazoline)-based chiral ligands are associated with copper to generate catalysts for the asymmetric benzoylation of meso-hydrobenzoin, the kinetic resolution of rac-hydrobenzoin and the asymmetric Henry reaction.

Chiral multidentate oxazoline ligands based on cyclophosphazene cores: synthesis, characterization and complexation studies

Chiral oxazoline based bi and hexadentate ligands built on cyclophosphazene cores have been synthesized and characterized. (NPPh2)2[NP(m-OC6H4C(O)OCH3)2] (1) was prepared by the reaction of gem-(NPPh2)2(NPCl2) with methyl-3-hydroxy benzoate in the presence of Cs2CO3. Compound 1 was converted to the dicarboxylic acid (NPPh2)2[NP(m-OC6H4C(O)OH)2] (2) by base promoted hydrolysis with KO(t-Bu). The dicarboxylic acid 2 on reaction with oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol, triethylamine and mesyl chloride was converted to the C2-symmetric phosphazene based chiral bisoxazoline ligand (NPPh2)2[NP{m-OC6H4(4-iPr-2-Ox)}2] (3) (Ox = oxazolinyl). A similar C2-symmetric bisoxazoline derivative having an oxazoline group attached to the para position of the phenyl ring was also synthesized starting from (NPPh2)2[NP(p-OC6H4C(O)OCH3)2] (4) which was first converted to the dicarboxylic acid (NPPh2)2[NP(p-OC6H4C(O)OH)2] (5) and finally to (NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (6) and (NPPh2)2[NP{p-OC6H4(4-Ph-2-Ox)}2] (7) under similar reaction conditions. Reaction of 6 with Pd(OAc)2 in acetic acid at room temperature and with PdCl2(C6H5CN)2 in refluxing benzene resulted in chiral palladium complexes Pd(OAc)2(NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (8) and PdCl2(NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (9), respectively. The utility of these palladium complexes as chiral catalysts for the asymmetric rearrangement of trichloroacetimidates to trichloroacetamides has been explored. The hexa(methylbenzoate) derivative of cyclophosphazene [PN(OC6H4COOCH3)2]3 (10) on treatment with KO(t-Bu) and H2O gave the hexacarboxylic acid derivative [PN(OC6H4COOH)2]3 (11), which on treatment with oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol/(S)-(+)-2-phenylglycinol, triethylamine and mesyl chloride was converted to the C3-symmetric cyclophosphazene based chiral hexaoxazoline ligands [PN{OC6H4(4-iPr-2-Ox)}2]3 (12) and [PN{OC6H4(4-Ph-2-Ox)}2]3 (13). The bis(phebox) derivative of the cyclophosphazene was prepared starting from (NPPh2)2[NP{OC6H3(COOCH3)2}2] (14), by the reaction of gem-Ph4P3N3Cl2 with dimethyl 5-hydroxyisophthalate in the presence of Cs2CO3. Compound 14 was converted to the tetracarboxylic acid (NPPh2)2[NP{OC6H3(COOH)2}2] (15) by base promoted hydrolysis with KO(t-Bu). The tetracarboxylic acid 15 on reaction with oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol/(S)-(+)-2-phenylglycinol, triethylamine and mesyl chloride was converted to the bis(phebox) substituted tetraphenylcyclophosphazene derivatives (NPPh2)2[NP{OC6H3(4-iPr-2-Ox)2}2] (16)/(NPPh2)2[NP{OC6H3(4-Ph-2-Ox)2}2] (17). A similar tetra(phebox) derivative was synthesized from (NPPh2)[NP{OC6H3(COOCH3)2}2]2 (18) which was first converted to (NPPh2)[NP{OC6H3(COOH)2}2]2 (19) and further converted to the tetra(phebox) derivative (NPPh2) [NP{OC6H3(4-Ph-2-Ox)2}2]2 (20). All new compounds were characterized by IR, NMR [(1)H, (13)C{(1)H} and (31)P{(1)H}] and HRMS studies. Compounds 1, 2, 4, 5, 7, 14 and 18 have also been structurally characterized.

ChemInform Abstract: Asymmetric Copper‐Catalyzed Diels—Alder Reaction Revisited: Control of the Structure of Bis(oxazoline) Ligands.

AbstractBisoxazolines bearing an ethanoanthracene backbone are reinvestigated as ligands in Cu‐catalyzed Diels—Alder reactions.

ChemInform Abstract: Carbenoid Insertions into Benzylic C—H Bonds with Heterogeneous Copper Catalysts.

AbstractCopper complexes with azabis(oxazoline) or bis(oxazoline) ligands, once supported on laponite clay by electrostatic interactions, are able to catalyze the insertion of carbenoids in benzylic C—H bonds.

ChemInform Abstract: Chiral Oxazoline Ligands Containing a 1,2,4‐Triazine Ring and Their Application in the Cu‐Catalyzed Asymmetric Henry Reaction.

Abstract 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).

Electronic effects of aryl-substituted bis(oxazoline) ligands on the outcome of asymmetric copper-catalysed C–H insertion and aromatic addition reactions

The effect of the modification of bis(oxazoline) ligands on the outcome of copper-catalysed C–H insertion and aromatic addition reactions is described. In general, these reactions display minimum sensitivity in terms of enantiocontrol to variation of the electronic properties of the aryl moiety of the ligand however, some influence is observed for C–H insertions employing naphthyl-substituted bis(oxazolines) and for aromatic addition reactions of biphenyl diazo ketone substrates. The synthesis of the modified bis(oxazolines), which include four novel structures, is also described.