Facile Ring Research Articles

Controlled semi‐Pinacol rearrangement on a strained ring: Efficient access to multi‐substituted cyclopropanes by group migration strategy

We describe a versatile electrophile addition/SPR sequence of readily available cyclopropyl carbinols that affords multi-substituted carbonylated cyclopropanes with high stereo-fidelity. This approach tolerates various heteroatom electrophiles, migration of carbon moiety of all possible hybridization states, facile ring reorganization and natural compound valorization. The examples represent an unprecedented version of SPR wherein migration to a non-benzylic bulky tertiary carbo-cation is realized with promising enantiocontrol.

Aromatic C–C Bond Cleavage in a Curved π-System of Aminocorannulene

We report a metal- and oxidant-free aromatic C-C bond cleavage in the curved corannulene skeleton. Reaction of 1-aminocorannulene with hydrazonyl chloride generates an amidrazone intermediate that undergoes facile intramolecular proton migrations and ring annulation to give a 1,2,4-triazole derivative of planar benzo[ghi]fluoranthene, in which the release of strain associated with the curved π-surface and the formation of an aromatic triazole moiety are the driving forces. This report provides new insights into the aromatic C-C bond cleavage.

Electrosynthesis of methyl 2-ureidobenzoates via a C2–C3 bond cleavage of isatins

A facile and efficient ring opening of isatin has been achieved by electrochemical anodic oxidation directly at room temperature. The results show that a constant current electrolysis of isatins in an undivided cell affords both the ester group and the urea group simultaneously. This reaction opens a new avenue for the synthesis of methyl 2-ureidobenzoates, enriches the research on the reactions of isatins involving the cleavage of the C2–C3 bond and shows a good range of substrates for both isatin and simple organic amine in an acidic buffer solutions of HOAc and Cu(OAc)2. In addition, this electrochemical C2–C3 bond cleavage reaction could be scaled up.

Pn Ring Size Dependence on NHC-Induced Ring Contraction Reactions of [CoCp‴(η4-P4)], [Ta(CO)2Cp″(η4-P4)], and [FeCp*(η5-P5)]: A DFT Study.

The facile ring contraction of [CoCp‴(η4-P4)] and [Ta(CO)2Cp″(η4-P4)] to [CoCp‴(η3-P3)][(MeNHC)2P] and [Ta(CO)2Cp″(η3-P3)] [(MeNHC)2P] induced by MeNHC and the absence of the ring contraction of [FeCp*(η5-P5)] under the same conditions are studied by density functional theory (DFT) computations. The latter is estimated to be thermodynamically the least favorable reaction and also has a very high energy barrier. The similar strain energies of P3 and P4 rings and the lower strain energy of the P5 ring play a decisive role in the ring contraction capability of these [TM-cyclo-Pn] complexes. Theoretical approaches involving NBO and IBO analysis have been employed to provide a qualitative picture of the overall reactions. The role of substituents and the nature of transition metals in determining the energetics of these reactions has also been studied and an isolobal perspective on these systems affords a simplified picture.

Reactivity of 1.1.1-Propellane with (silox)3M (M = Ti, V, Cr): Structures of (silox)3V═(cC4H4)═CH2 and [(silox)3Cr–(1.1.1-C5H6)−]2

Application of the two-orbital, two-electron, four-state paradigm to 1.1.1-propellane (111P), which contains an unusual “inverted” central bond, suggests that an electrophilic metal center can activate it toward ring opening. Low-valent, early-metal complexes ((silox)3M (M = Ti (1), V (2) (or M = V(THF) (2-THF), Cr (3))) were employed to test this assessment with mixed results. Facile ring opening of 111P occurs for 1, producing known degradation products, and 2, which generates the alkylidene (silox)V═(cC4H4)═CH2 (2═C5H6), a species capable of catalyzing the ROMP (ring-opening metathesis polymerization) of norbornene. For 3 and 111P, a radical-like dimerization to [(silox)3Cr-(1.1.1-C5H6)−]2 (or (silox)3Cr(C5H6)2Cr(silox)3 (32P2)) effectively competes with ring opening. In conjunction with the experiments, high-level calculations provide a rationale for the trichotomy in reactivity.

Localized Antiaromaticity Hotspot Drives Reductive Dehydrogenative Cyclizations in Bis- and Mono-Helicenes.

We describe reductive dehydrogenative cyclizations that form hepta-, nona-, and decacyclic anionic graphene subunits from mono- and bis-helicenes with an embedded five-membered ring. The reaction of bis-helicenes can either proceed to the full double annulation or be interrupted by addition of molecular oxygen at an intermediate stage. The regioselectivity of the interrupted cyclization cascade for bis-helicenes confirms that relief of antiaromaticity is a dominant force for these facile ring closures. Computational analysis reveals the unique role of the preexisting negatively charged cyclopentadienyl moiety in directing the second negative charge at a specific remote location and, thus, creating a localized antiaromatic region. This region is the hotspot that promotes the initial cyclization. Computational studies, including MO analysis, molecular electrostatic potential maps, and NICS(1.7)ZZ calculations, evaluate the interplay of the various effects including charge delocalization, helicene strain release, and antiaromaticity. The role of antiaromaticity relief is further supported by efficient reductive closure of the less strained monohelicenes where the relief of antiaromaticity promotes the cyclization even when the strain is substantially reduced. The latter finding significantly expands the scope of this reductive alternative to the Scholl ring closure.

Utilization of CO2-Available Organocatalysts for Reactions with Industrially Important Epoxides

Recent knowledge in chemistry has enabled the material utilization of greenhouse gas (CO2) for the production of organic carbonates using mild reaction conditions. Organic carbonates, especially cyclic carbonates, are applicable as green solvents, electrolytes in batteries, feedstock for fine chemicals and monomers for polycarbonate production. This review summarizes new developments in the ring opening of epoxides with subsequent CO2-based formation of cyclic carbonates. The review highlights recent and major developments for sustainable CO2 conversion from 2000 to the end of 2021 abstracted by Web of Science. The syntheses of epoxides, especially from bio-based raw materials, will be summarized, such as the types of raw material (vegetable oils or their esters) and the reaction conditions. The aim of this review is also to summarize and to compare the types of homogeneous non-metallic catalysts. The three reaction mechanisms for cyclic carbonate formation are presented, namely activation of the epoxide ring, CO2 activation and dual activation. Usually most effective catalysts described in the literature consist of powerful sources of nucleophile such as onium salt, of hydrogen bond donors and of tertiary amines used to combine epoxide activation for facile epoxide ring opening and CO2 activation for the subsequent smooth addition reaction and ring closure. The most active catalytic systems are capable of activating even internal epoxides such as epoxidized unsaturated fatty acid derivatives for the cycloaddition of CO2 under relatively mild conditions. In case of terminal epoxides such as epichlorohydrin, the effective utilization of diluted sources of CO2 such as flue gas is possible using the most active organocatalysts even at ambient pressure.

Osmium(II)-Coordination Induced C-C Bond Functionalization of Bis-lawsone.

Metal-coordination-driven C-C bond functionalization without involvement of the traditional route of oxidative addition, insertion, and reductive elimination has gained immense importance. In this context, the present Communication highlights the facile ring contraction process of the deprotonated bis-lawsone (L2-) to functionalized L12- upon coordination to {Os(bpy)2} or isomeric {Os(pap)2} (bpy = 2,2'-bipyridine and pap = 2-phenylazopyridine) in 1-3. Further, recognition of fractional redox noninnocence of L1 in 1+-3+ via experimental and theoretical events facilitated its inclusion in the redox noninnocent family.

Ruthenium-Hydride Assisted Remarkable Diversity Towards Non-Spectator Feature of Benzodifuroxan.

The present article demonstrates that ruthenium-hydride [RuII (H)(Cl)(CO)(PPh3 )3 ] mediated diverse functionalization modes of benzodifuroxan (BDF) encompassing two furoxan rings. Hydride transfer from the metal precursor facilitated multiple cascade reactions involving unsymmetrical cleavage of the furoxan rings of BDF, leading to the one-pot formation of a series of ruthenium (II) coordinated functionalized ligands exhibiting bidentate κ2 -N,O, κ2 -N,N' and bis-bidentate μ-bis(κ2 -N,O) modes. Further, a moderately stable intermediate species was also encountered in the reaction sequence in which the transformed deoxygenated ligand coordinated to the metal ion via the rarely manifested furazan ring (κ2 -N,N'' mode). The products were authenticated by their single-crystal X-ray structures and other spectroscopic/analytical techniques. Redox non-innocence of the functionalized ligands in the complexes was illustrated by spectroelectrochemistry (cyclic voltammmetry, UV-Vis. and EPR) in conjunction with DFT/TD-DFT calculations. Mechanistic outline for the facile ring opening processes of BDF including interconversions of complexes (e. g. reductive ring opening) were also addressed.

Experimental and Computational Studies of Microwave-Assisted, Facile Ring Opening of Epoxide with Less Reactive Aromatic Amines in Nitromethane.

Nucleophilic ring opening reactions of epoxides with aromatic amines are in the forefront of the synthetic organic chemistry research to build new bioactive scaffolds. Here, convenient, green, and highly efficient regioselective ring opening reactions of sterically hindered (2R,3S)-3-(N-Boc-amino)-1-oxirane-4-phenylbutane with various poorly reactive aromatic amines are accomplished under microwave irradiation in nitromethane. All the reactions effectively implemented for various aromatic amines involve the reuse of nitromethane that supports its dual role as a solvent and catalyst. The corresponding new β-alcohol analogs of hydroxyethylamine (HEA) are isolated in 41–98% yields. The reactions proceed under mild conditions for a broad range of less reactive and sterically hindered aromatic amines. Proton NMR experiments suggest that the nucleophilicity of amines is influenced by nitromethane, which is substantiated by the extensive computational studies. Overall, this methodology elucidates the first-time use of nitromethane as a solvent for the ring opening reactions under microwave conditions involving an equimolar ratio of epoxide and aromatic amine without any catalyst, facile ring opening of complex epoxide by less reactive aromatic amines, low reaction time, less energy consumption, recycling of the solvent, and simple workup procedures.

2+2] Photochemical Cycloaddition in Organic Synthesis

The century old [2+2] photocycloaddition reaction appeared as the most synthetically useful reaction amongst all photochemical reactions. It provides not only cyclobutane ring systems, but at the same time it provides access to medium rings through facile ring expansion/fragmentation of the strained cyclobutane ring. The high regio‐and stereoselectivity observed during cycloaddition has made it an attractive tool for synthesis of multicyclic structurally complex natural products. The vast majority of [2+2] photocycloaddition reactions involves enone–alkene cycloaddition which is conveniently achieved through direct excitation or sensitization by UV irradiation. Substantial progress has also been made in [2+2] cycloaddition between two unactivated alkenes using transition metal salts especially copper(I) salts. Sometimes Cu(I)‐catalyzed cycloaddition is advantageous over enone–alkene photocycloaddition. Search for an alternative source to environmentally harmful high energy UV light has led to the discovery of transition metal salts which can be used to excite alkenes by visible light. This causes alkenes to undergo [2+2] cycloaddition and has been used for synthesis of cyclobutane derivatives. This review aims to give an overview about different aspects of [2+2] photocycloaddition reaction with an emphasis in the stereoselective synthesis of selected complex natural products and related molecules where cycloaddition has been used as the key step.

Phosphaaluminirenes: Synthons for Main Group Heterocycles.

The phosphaaluminirenes HC[(CMe)(NDipp)]2Al[C(R)═P] (Dipp = 2,6-i-Pr2C6H3, R = tBu or adamantyl) 2 and 3, featuring an unsaturated three-membered AlCP ring, have been synthesized as crystalline solids via a [1 + 2] cycloaddition reaction of the aluminum(I) complex HC[(CMe)(NDipp)]2Al (1) with phosphaalkynes. Computational investigations infer three-centered 2π-electron aromaticity of the AlCP rings. Compound 3 is readily protonated by tBuOH to induce a ring-opening σ-bond metathesis, giving an alumina-substituted P-hydrogeno phosphaalkene 4. Remarkably, the high strain of the AlCP ring of 3 allows for facile ring enlargement in reactions with CyNC, bis(diisopropylamino) cyclopropenylidene (BAC), elemental Se, Ph2CO, PhCH═CHCOPh, and PhCN at room temperature. These furnish a series of unprecedented main group heterocycles 5-10 with the C═P unsaturated bonds remaining intact. The mechanisms are considered in light of thorough density functional theory (DFT) calculations.

Cure kinetics of epoxy/graphene oxide (GO) nanocomposites: Effect of starch functionalization of GO nanosheets

Graphene oxide (GO) nanoflakes are reactive towards both epoxy resin and amine curing agent, but their inevitable agglomeration worsens resin/hardener/nanoflake interfacial interactions. In this work, starch was used to functionalize GO nanoflakes. Isoconversional cure kinetics of low concentration epoxy/GO and epoxy/starch-functionalized GO (GO-St) nanocomposites was then studied based on nonisothermal differential scanning calorimetry (DSC) analyses to evaluate the effect of starch-aided epoxy/amine/GO curing reactions. Qualitative analysis of epoxy network formation governed by GO and GO-St was done in terms of Cure Index, where Good and Excellent cure were interestingly observed as a result of starch functionalization. Quantitative cure analyses based on integral and differential isoconversional methods were also allowed for understanding conversion-dependent cure kinetics in terms of activation energy (Eα) alteration. The activation energy increased for neat epoxy system at later stage of curing reaction. However, an almost constant trend was seen for the activation energy of GO incorporated epoxy nanocomposites. Observation of a decline in Eα values for epoxy/GO-St system with respect to epoxy/GO was due to the autocatalytic curing reaction, which was attributed to facile epoxide ring opening by OH groups of starch. A good confidence was observed between calculated and observed calorimetric data.

A Quencher‐Fluorophore‐Type Probe for Detection and Imaging of NADPH in Human Breast Cancer Cells

A new fluorogenic trimethyl lock quinone (TLQ) derivative, designated as the quencher‐TLQ‐fluorophore‐type probe (Q‐TLQ‐F), was developed for selective detection of nicotinamide adenine dinucleotide phosphate (NADPH). By taking advantage of the well‐known facile intramolecular ring cyclization reaction (δ‐lactonization) of TLQ that can release a reporter molecule upon reduction, Q‐TLQ‐F was successfully applied for the detection of physiological NADPH generated by glucose‐6‐phosphate dehydrogenase in human breast cancer MDA‐MB‐231 cells.

Ring-Opening Functionalization of Simple gem-Difluorocyclopropanes by Single-Electron Oxidants.

It was reported for the first time that single-electron oxidants such as CAN or K2S2O8 affected facile ring opening of simple gem-difluorocyclopropanes to afford 1,3-dibromo-2,2-difluoropropanes in good yields by the action of KBr, and the appropriate choice of conditions allowed to incorporate not only second halogen atoms but also hydroxy or acetamido groups at the C1 position in the difluoropropane structures in a regiospecific fashion after initiation of the reaction by the introduction of the first bromine atom at the C3 position.

Ligand Noninnocence in Nickel Porphyrins: Nickel Isobacteriochlorin Formation under Hydrogen Evolution Conditions.

An electron-deficient nickel porphyrin complex undergoes facile ring reduction to form a nickel isobacteriochlorin complex under hydrogen evolution conditions. Spectroscopic experiments indicate that the reduced nickel porphyrin undergoes subsequent reduction and protonation to form a phlorin anion rather than a metal hydride, demonstrating that the key initial proton-coupled electron transfer step is directed toward the ligand versus the metal. The phlorin anion facilely converts to the isobacteriochlorin in the presence of two-electron and three-proton equivalents. Cyclic voltammetry (CV) and spectroscopic experiments reveal that the four-electron, four-proton electrochemical reduction of nickel porphyrin to isobacteriochlorin occurs promptly in the presence of the strong proton donor tosic acid, followed by hydrogen evolution reaction (HER) catalysis at slightly more negative potentials. CVs of independently synthesized Ni isobacteriochlorin show a catalytic HER at the same potentials as those observed for the HER in CVs of the Ni porphyrin. We find that, under strongly acidic conditions, the HER catalysis arises from conversion of the Ni isobacteriochlorin into a nickel-containing, catalytically active electrode-adsorbed species. These results show that Ni porphyrin converts to Ni isobacteriochlorin under HER catalysis conditions via a ligand-based PCET process and that it is the isobacteriochlorin complex which gives rise to an active HER catalysis.

Microwave-assisted synthesis of 3-aminoarylquinolines from 2-nitrobenzaldehyde and indole via SnCl2-mediated reduction and facile indole ring opening

A simple and efficient one-pot two-step synthesis of substituted 3-aminoarylquinolines has been achieved from 2-nitrobenzaldehyde and indoles under microwave irradiation. Firstly 2-nitrobenzaldehydes is reduced to 2-aminobenzaldehyde in situ by commonly used chemo selective reductant SnCl2 followed by condensation of indole. The acidic nature of the resultant reaction mixture due to SnCl2 helps in the condensation and facile ring opening of indole leading to the formation of 3-aminoarylquinoline derivatives in good to moderate yields.

Facile catalytic ring opening polymerization of lactic acid: Comparing the performance of Fe and Zn metal species

As a bio‐compatible/degradable polymer, poly(lactic acid) (PLA) has been widely noticed in tissue engineering and medical applications. Proper catalytic ring‐opening polymerization of lactic acid is pertinent to development of active metal species capable of producing high‐molecular‐weight polymers. In this work, ligand catalyst (2,4‐di‐tertio‐butyl‐6‐{[(2‐di‐methyl‐amino ethyl) methyl amino] methyl} phenol) was synthesized and then attached to Fe‐based and Zn‐based metal substitutes, and performance of metal species toward ring opening polymerization of lactic acid has been investigated. Regulation of reaction condition at 180°C for 36 h with Zn‐based catalyst allowed for late‐stage production of a high‐molecular‐weight PLA, while Fe‐based facilitated polymerization at early stages leading to PLAs with comparatively twofold higher molecular weight at lower time, monomer‐to‐initiator ratio, and temperature (at 170°C). A ratio of monomer to initiator of 5000 with Fe catalyst resulted in the highest molecular weight. Thus, polymerization has been facilitated by the use of Fe‐based catalyst. For this class of catalyst with Fe substitute, the product was characterized by means of 1H‐NMR, Fourier transform infrared spectroscopy, and differential scanning calorimetry analyses. J. VINYL ADDIT. TECHNOL., 25:215–224, 2019. © 2018 Society of Plastics Engineers

Harnessing the Polarizability of Conjugated Alkynes toward [2 + 2] Cycloaddition, Alkenylation, and Ring Expansion of Indoles

Reported is the utilization of electronically biased conjugated alkynes in the development of highly diastereo- and regioselective dearomative [2 + 2] cycloadditions, alkenylations, and ring expansions of electron-rich indoles. Regioselective protonations of cross- and linear-conjugated alkynes were found to be crucial for accessing various cyclobutene-fused indoline and alkenylated indole derivatives. Furthermore, the facile ring expansion of [2 + 2] keto adducts, which were successfully synthesized from ynones, provided 1 H-benzo[ b]azepine scaffolds.

A Facile Epoxide Aminolysis Promoted by (t-BuO)2Mg and Its Application to the Synthesis of Efinaconazole

A novel and efficient method for the aminolysis of trizole epoxides is described. This method consists of a facile ring opening of the epoxides mediated by t-BuOMgCl generated in situ from amine hydrochlorides and (t-BuO)2Mg. The desired β-amino alcohols were obtained in good yields without employing other heavy metals or precious catalysts. The optimized conditions were successfully applied to the synthesis of a number of potential triazole antifungal compounds as well as efinaconazole on up to a 700 g scale.