Selective Ring-opening Reaction Research Articles

Palladium-Catalyzed Ring-Opening Reaction of Cyclopropenones with Vinyl Epoxides.

We report herein the Pd-catalyzed selective ring-opening reaction of cyclopropenones with vinyl epoxides. By using a commercially available Pd2(dba)3·CHCl3-BINAP catalyst, a wide range of conjugated alkadienyl carboxylates could be accessed in good yield and excellent regioselectivity. The new application of zwitterionic π-allyl palladium intermediates has been demonstrated in organic synthesis.

Synthesis of Titanium Complexes Supported by Carbinolamide- and Amide-Containing Ligands Derived from Ti(NMe2)4-Mediated Selective Amidations of Carbonyl Groups.

An efficient strategy for the syntheses of a series of titanium complexes has been developed. This protocol features the employment of Ti(NMe2)4 both as the metal center to trigger the deprotonation of the ligands and as an amine source to proceed the amidation reactions of carbonyl functionalities of the ligands. Treatment of Ti(NMe2)4 with a ligand HL1 (HL1 = 2,2'-(((2-hydroxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) results in the formation of Ti(L1')(NMe2) (1) (H3L1' = N1-(2-((2-(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxybenzyl)amino)ethyl)-N2,N2-dimethylphthalamide). One important feature regarding the synthesis of 1 is the occurrence of the in situ metal-ligand reaction between Ti(NMe2)4 and HL1, leading to the simultaneous formations of carbinolamide and amide scaffolds. Another prominent feature in terms of the preparation of 1 is the achievement of the selective ring-opening reaction of one of the two phthalimide units of the HL1 ligand, affording carbinolamide and amide functionalities within one ligand set. The developed methodology characterizes an ample substrate scope. The selective amidation reactions of the carbonyl groups have been realized for a series of analogous ligands HL2-HL7. Density functional theory calculations were employed to disclose the mechanisms for the formation of 1-7, and the details for the selective ring-opening reactions of the phthalimide unit were uncovered.

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions.

The selective ring-opening reaction of fluoroalkylidene-oxetanes was directed by the presence of the fluorine atom, enabling a two-step access to tetrasubstituted fluoroalkenes with excellent geometry control. Despite its small van der Waals radii electronic, rather than steric influences of the fluorine atom governed the ring-opening reaction with bromide ions, even in the presence of bulky substituents.

Dibora[10]annulenes: Construction, Properties, and Their Ring-Opening Reactions.

The selective construction of various dibora[10]annulenes through mild boron-tin exchange reactions is reported. Dibora[10]annulenes exhibit optical and electrochemical properties of value for future sensing applications. Controlled addition of the Lewis base pyridine to dibora[10]annulenes instigates a selective ring-opening reaction. This work explores a new area of boron chemistry that represents the first step in the potential formation of dibora[10]annulene-derived polymers.

Preparation of a highly efficient Pt/USY catalyst for hydrogenation and selective ring-opening reaction of tetralin

Ultrastable Y zeolite (USY)-supported Pt catalyst was prepared by gas-bubbling-assisted membrane reduction. The influence of reaction conditions and the metal and acid sites of catalysts on the catalytic performance of catalyst in hydrogenation and selective ring opening of tetralin, 1,2,3,4-tetrahydronaphthalene (THN), was studied. It was found that the optimal reaction conditions were at a temperature of 280 °C, hydrogen pressure of 4 MPa, liquid hourly space velocity of 2 h−1 and H2/THN ratio of 750. Under these optimal conditions, a high conversion of almost 100% was achieved on the 0.3Pt/USY catalyst. XRD patterns and TEM images revealed that Pt particles were highly dispersed on the USY, favorable to the hydrogenation reaction of tetralin. Ammonia temperature-programmed desorption and Py-IR results indicated that the introduction of Pt can reduce the acid sites of USY, particularly the strong acid sites of USY. Thus, the hydrocracking reaction can be suppressed.

Rational synthesis of silylated Beta zeolites and selective ring opening of 1-methylnaphthalene over the NiW-supported catalysts

Heavy oil has been by-produced from refinery and petrochemical processes, and its use as low-value fuels has been restricted by stricter environmental regulations due to heavy molecules, multi-ring aromatics, and high sulfur content. In a bi-functional catalyst system of metal and zeolitic acid, balancing metallic (from metal element) and acidic function (from zeolite elements) is essential for harnessing the selective ring opening (SRO) reaction with the aim of upgrading the heavy oil. Here, we report a synthetic strategy to control the acid site distribution of Beta zeolite through the silylation reaction with tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate (TEOS), and tetrabutyl orthosilicate (TBOS) as silylation agents. As the size of alkyl chain group in the silylation agents gets larger, the silylation agents were suppressed to spread into the channels and thus the formation of SiO2 layer was intentionally occurred on the external surface of the zeolite. Resulting from the selectively deposited SiO2 layer, NiW metals supported on each silylated Beta zeolite altered the metal distribution and further the balance of metallic and acidic function. NiW catalyst supported on TBOS-silylated Beta zeolite exhibited the best catalytic performance toward the SRO reaction of 1-methylnaphthalene in a fix-bed reaction system, proving the optimal balance of metallic and acidic functions. We expect that this study will benefit the control over the selective silylation reaction in order to optimize the balance of metallic and acidic functions in the bi-functional catalysts, and, hence, to promote properly aromatic saturation (hydrogenation) and ring opening (hydrocracking) for selective ring opening products.

Selective Ring-Opening of N-Alkyl Pyrrolidines with Chloroformates to 4-Chlorobutyl Carbamates.

Our study shows that among aza-heterocycles of various ring sizes, including aziridines, azetidines, pyrrolidines, and piperidines, only N-alkyl pyrrolidines undergo competitive reaction pathways with chloroformates to yield N-dealkylated pyrrolidines and 4-chlorobutyl carbamates. The pathway taken depends on the substituent on the nitrogen, i.e., ring-opening with methyl and ethyl substituents and dealkylation with a benzyl substituent. Computational calculations support the substituent-dependent product formation by showing the energy difference between the transition states of both reaction pathways. Selective ring-opening reactions of N-methyl and N-ethyl pyrrolidine derivatives with chloroformates were utilized to prepare various 4-chlorobutyl carbamate derivatives as valuable 1,4-bifunctional compounds.

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)-Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures.

Cobalt(II)-based metalloradical catalysis (MRC) has been successfully applied for effective construction of the highly strained 2-sulfonyl-1,3-diazabicyclo[3.1.0]hexane structures in high yields through intramolecular radical aziridination of allylic sulfamoyl azides. The resulting [3.1.0] bicyclic aziridines prove to be versatile synthons for the preparation of a diverse range of 1,2- and 1,3-diamine derivatives by selective ring-opening reactions. As a demonstration of its application for target synthesis, the metalloradical intramolecular aziridination reaction has been incorporated as a key step for efficient synthesis of a potent neurokinin 1 (NK1 ) antagonist in 60 % overall yield.

The Effect of K and Acidity of NiW-Loaded HY Zeolite Catalyst for Selective Ring Opening of 1-Methylnaphthalene.

Bi-functional catalysts were prepared using HY zeolites with various SiO2/Al2O3 ratios for acidic function, NiW for metallic function, and K for acidity control. 1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in heavy oil, and its selective ring opening reaction was investigated using the prepared bi-functional catalysts with different levels of acidity in a fixed bed reactor system. In NiW/HY catalysts without K addition, the acidity decreased with the SiO2/Al2O3 mole ratio of the HY zeolite. Ni1.1W1.1/HY(12) catalyst showed the highest acidity but slightly lower yields for the selective ring opening than Ni1.1W1.1/HY(30) catalyst. The acidity of the catalyst seemed to play an important role as the active site for the selective ring opening of 1-methylnaphthalene but there should be some optimum catalyst acidity for the reaction. Catalyst acidity could be controlled between Ni1.1W1.1/HY(12) and Ni1.1W1.1/HY(30) by adding a moderate amount of K to Ni1.1W1.1/HY(12) catalyst. K0.3Ni1.1W1.1/HY(12) catalyst should have the optimum acidity for the selective ring opening. The addition of a moderate amount of K to the NiW/HY catalyst must improve the catalytic performance due to the optimization of catalyst acidity.

Selective Ring Opening of 1-Methylnaphthalene Over NiW-Supported Catalyst Using Dealuminated Beta Zeolite.

Nanoporous Beta zeolite was dealuminated by weak acid treatment for reducing the acidity. Bi-functional catalysts were prepared using commercial Beta zeolites and the dealuminated zeolites for acidic function, NiW for metallic function. 1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in heavy oil, and its selective ring opening reaction has been investigated using the prepared bi-functional catalysts with different acidity in fixed bed reaction system. The dealuminated Beta zeolites, which crystal structure and nanoporosity were maintained, showed the higher SiO2/Al2O3 ratio and smaller acidity than their original zeolite. NiW-supported catalyst using the dealuminated Beta zeolite with SiO2/Al203 mole ratio of 55 showed the highest performance for the selective ring opening. The acidity of catalyst seemed to play an important role as active sites for the selective ring opening of 1-methylnaphthalene but there should be some optimum catalyst acidity for the reaction. The acidity of Beta zeolite could be controlled by the acid treatment and the catalyst with the optimum acidity for the selective ring opening could be prepared.

Scandium triflate-catalyzed selective ring opening and rearrangement reaction of spiro-epoxyoxindole and carbonyl compounds

Scandium triflate-catalyzed reactions between spiro-epoxyoxindole and carbonyl compounds have been disclosed. Furthermore, an unprecedented rearrangement takes place to yield alkylidene oxindoles when aromatic aldehydes are used as carbonyl components.

Theoretical Studies of Ring-Opening Reactions of Phenylcyclobutabenzenol and Its Reactions with Alkynes Catalyzed by Rhodium Complexes

DFT calculations have been carried out to study the Rh-catalyzed site selective ring-opening reactions of phenylcyclobutabenzenol (1a). Our calculations supported that the mechanism involves β-carbon elimination in a rhodium(I) phenylcyclobutabenzenolato complex followed by alcoholysis. The favorable β-carbon elimination involves the cleavage of the C(sp(2))-C(sp(3))(OH)(Ph) bond in 1a, which determines the site selectivity. The mechanism and regioselectivity of the related Rh-catalyzed insertion reaction of the asymmetric alkyne MeC≡CPh with phenylcyclobutabenzenol (1a) was also investigated. The key step involves the alkyne insertion into the Rh-C σ bond of a species resulting from the favorable β-carbon elimination in the rhodium(I) phenylcyclobutabenzenolato complex. The favorable insertion couples the metal-bonded carbon with the methyl-substituted carbon of MeC≡CPh.

Determination of critical micelle concentration of dendritic surfactant synthesized via a selective ring-opening addition reaction

An azetidine-2,4-dione was applied to synthesize dendrons with four carbons in the end ([G-0.5]-C4 and [G-1]-C4) via a selective ring-opening addition reaction, which was subsequently extended to obtain a dendritic surfactant ([G-1]-C4 surfactant) by acidification. The dendrons were characterized by Fourier transform infrared (FT-IR), 1H nuclear magnetic resonance (1H NMR), elemental analyzer (EA), and fast atom bombardment mass spectrometry (FAB MS). The dendritic surfactant, with a cationic head and branched hydrophobic C4 tails, was dissolved in 2wt.% dimethyl sulfoxide (DMSO) aqueous solution for the determination of critical micelle concentration (CMC) by fluorescence and electrical conductivity measurements. The resulted CMC values were very close within measurements, ca. 0.013–0.05mM. Transmission electron microscopy (TEM) and zeta potential measurement also provided an evidence of micelle formation and shape. Moreover, anionic dyes were adsorbed onto the micelles successfully to confirm the positive charge of [G-1]-C4 surfactant.

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

tert-Butyl cinnamates are aziridinated with high trans-selectivity by an N–N ylide generated in situ from N-methylmorpholine and O-diphenylphosphinyl hydroxylamine. The resulting N-unfunctionalised aziridines are shown to be versatile synthetic building blocks that undergo highly selective ring-opening reactions with a wide range of nucleophiles.

A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (−)-shikimic acid

New synthesis of oseltamivir phosphate was accomplished in 9 steps with a 27% overall yield from a readily available (−)-shikimic acid. Selective ring opening reaction of ketal and azide Mitsunobu reaction for facile replacement of a hydroxyl group by the N3 group at the C-3 position of (3R,4R,5R)-ethyl 4-hydroxy-5-(methoxymethoxy)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 4 and at the C-4 position of (3R,4S,5R)-ethyl 4-acetamido-5-hydroxy-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 7 successfully served as the key steps.

Metal-Assisted Ring-Closing/Opening Process of a Chiral Tetrahydroquinazoline

The ring-chain tautomerism of a 2-aryl-1,2,3,4-tetrahydroquinazoline has been exploited to induce reversible changes in the aminal-imine equilibrium, as desired, by coordination of a suitable metal ion. This process was studied by NMR and UV-vis spectroscopies, X-ray crystallography, and molecular modeling approach. The results obtained show that the imine H(2)L(i) undergoes a selective ring-closing reaction upon complexation with Ni(2+). As a result, complexes of the type Ni(HL(a))(2) are obtained, whose chirality arises from the chiral ligand H(2)L(a) and the helicity of the structure. Hence, helical enantiomers form the following racemates: [Δ-C(R,R)N(S,S),Λ-C(S,S)N(R,R)]-Ni(HL(a))(2)·2HOAc and [Δ,Λ-C(S,R)N(R,S)]-Ni(HL(a))(2)·4MeOH. In contrast to the situation observed for Ni(2+), the cyclic tautomer of the ligand, H(2)L(a), undergoes a selective ring-opening reaction upon complex formation with Pd(2+), ultimately yielding Pd(HL(i))(2)·MeOH, in which the open-chain imine ligand is bidentate through the N,O donor set of the quinoline residue. Density functional theory calculations were conducted to provide insight into the different behavior of both coordinated metals (Ni(2+) and Pd(2+)) and to propose a mechanism for the metal-assisted opening/closing reaction of the tetrahydroquinazoline ring.

ChemInform Abstract: Synthesis of 1,2,3,4,5,7‐Hexahydro‐6H‐azocino[4,3‐b]indol‐6‐ones as Intermediates for the Synthesis of Apparicine.

AbstractPyrrolidone (I) undergoes a selective ring opening reaction upon reaction with lithiated phenylsulfonylindole (II) generating key ketone (III), whose acidic N‐hydrogen can be utilized for further N‐alkylations.

Synthesis of first row transition metal carboxylate complexes by ring opening reactions of cyclic anhydrides

Hydrolytic and solvolytic ring opening reactions of phthalic anhydride, pyromellitic dianhydride and 2,3-pyridine dicarboxylic anhydride in the presence of various transition metal salts with or without a ancillary ligands were studied. The reactions were found to be dependent on stoichiometry of ligand and types of anhydride used. In the case of pyromellitic dianhydride selective ring opening reaction by cobalt(II) ions gave 1,3-benzene dicarboxylate derivatives, whereas use of copper(II) ions gave 1,4-benzene dicarboxylate derivatives. Preference for methanolysis was seen in the case of copper (II) promoted reactions of pyromellitic dianhydride in the presence of 1:1 metal to 1,10-phenanthroline ratio. Ring opening reactions of phthalic anhydride, pyromellitic dianhydride and 2,3- pyridine dicarboxylic anhydride to prepare various transition metal complexes are discussed. The selectivity on methanolysis is controlled by stoichiometry of nitrogen donor ligands, and position of ring opening is governed by metal ions.

Hg2+-Reactive Double Hydrophilic Block Copolymer Assemblies as Novel Multifunctional Fluorescent Probes with Improved Performance

We report on novel type of responsive double hydrophilic block copolymer (DHBC)-based multifunctional chemosensors to Hg(2+) ions, pH, and temperatures and investigate the effects of thermo-induced micellization on the detection sensitivity. Well-defined DHBCs bearing rhodamine B-based Hg(2+)-reactive moieties (RhBHA) in the thermo-responsive block, poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-RhBHA) (PEO-b-P(NIPAM-co-RhBHA)), were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Nonfluorescent RhBHA moieties are subjected to selective ring-opening reaction upon addition of Hg(2+) ions or lowering solution pH, producing highly fluorescent acyclic species. Thus, at room temperature PEO-b-P(NIPAM-co-RhBHA) DHBCs can serve as water-soluble multifunctional and efficient fluorescent chemosensors to Hg(2+) ions and pH. Upon heating above the lower critical solution temperature (approximately 36 degrees C) of the PNIPAM block, they self-assemble into micelles possessing P(NIPAM-co-RhBHA) cores and well-solvated PEO coronas, which were fully characterized by dynamic and static laser light scattering. It was found that the detection sensitivity to Hg(2+) ions and pH could be dramatically improved at elevated temperatures due to fluorescence enhancement of RhBHA residues in the acyclic form, which were embedded within hydrophobic cores of thermo-induced micellar aggregates. This work represents a proof-of-concept example of responsive DHBC-based multifunctional fluorescent chemosensors for the highly efficient detection of Hg(2+) ions, pH, and temperatures with tunable detection sensitivity. Compared to reaction-based small molecule Hg(2+) probes in previous literature reports, the integration of stimuli-responsive block copolymers with well-developed small molecule-based selective sensing moieties in the current study are expected to exhibit preferred advantages including enhanced detection sensitivity, water dispersibility, biocompatibility, facile incorporation into devices, and the ability of further functionalization for targeted imaging and detection.

Synthesis of N-isobutylnoroxymorphone from naltrexone by a selective cyclopropane ring opening reaction

Selective ring opening reaction of the N-cyclopropylmethyl group in naltrexone ( 1d) was effected in the presence of platinum (IV) oxide and hydrobromic acid under a hydrogen atmosphere at rt to selectively afford N-isobutyl derivative 10. The binding affinity of N- i-Bu derivative 10 for opioid receptors was 11–17 times less than that of the corresponding N-CPM compound, naltrexone ( 1d). However, compound 10 showed dose-dependent analgesic effects. Contrary to expectations based on previous structure–activity relationship studies for a series of N-substituted naltrexone derivatives that compound 10 would be an opioid antagonist, 10 showed dose-dependent analgesia in the mouse acetic acid writhing test (ED 50: 5.05 mg/kg, sc), indicating it was an opioid agonist. This finding may have a great influence on the drug design of opioid agonists.