Ring-expanded Products Research Articles

Brønsted acid mediated alkenylation and copper-catalyzed aerobic oxidative ring expansion/intramolecular electrophilic substitution of indoles with propargyl alcohols: a novel one-pot approach to cyclopenta[c]quinolines.

Copper-catalyzed oxidative ring-expansion/intramolecular electrophilic substitution of 3-dienylindoles leading to cyclopenta[c]quinolines and 3-indenylindoles under aerobic conditions is described. The precursors, 3-dienylindoles, are formed via Friedel-Crafts alkenylation followed by isomerization reactions of 2-substituted indoles with tertiary propargyl alcohols under Brønsted acid mediation. The methyl (sp(3)-C) group present in the propargyl alcohol becomes a part of a six-membered ring in the final ring-expansion products, the cyclopenta[c]quinolines which are fluorescence active. Based on these observations, a novel one-pot strategy for ring expansion from indole to cyclopenta[c]quinoline is discovered.

ChemInform Abstract: A Concise Approach Toward Tetrazolyl‐Substituted Benzazocines via a Novel Isocyanide‐Based Multicomponent Reaction.

The synthesis of pharmacologically relevant isoquinoline-tetrazoles and benzazocine-tetrazoles via sequential azido-Ugi and alkyne-induced ring-expansion reactions starting from cotarnine chloride are reported. A one-pot, multicomponent reaction protocol toward the ring-expanded product is also described.

Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues.

Shortcut Approach to 1,4-Diazepine from 3-Pyridylnitrene Intermedietes under Mild Condition

The reaction of nitropyridine derivatives and tributylphosphine (Bu 3 P) with the existence of nucleophilic solvent gives ring expansion product as diazepines in medium yield. Reaction mechanism subjected the formation of phenylnitrene, followed by intramolecular electrophilic insertion reaction to pyridine ring and subsequent ring enlargement. The intermediate in the reaction confirmed by computational calculation using B3LYP/6-31G* level. The intramolecular insertion reaction of pyridylnitrene is considered suppressed by the low HOMO (-9.932 eV) energy level of pyridine ring compared to that of benzene (-9.653 eV), hence 1,4-diazepine is obtained when employed 3-nitro-2,6-lutidine as starting material. The formation of diazepines was confirmed by the analysis of 1 H NMR data. Separation of the product mixture using column chromatography on SiO 2 was carried out and found to give expected diazepine along with the reduction product.

Systematic investigation of the ring-expansion reaction of N-heterocyclic carbenes with an iminoborane dihydride.

Conversions of iminoboranes with an N-heterocyclic carbene (NHC) result in borane dihydride formation (BDF) concomitant with dihydrogenated NHC. The iminoborane dihydrides are prone to a hydride-mediated ring-expansion reaction (RER) at elevated temperature, that is, the insertion of the boron atom into the adjacent CN bond of the NHC to yield boracycles. Upon conversion of a saturated-backbone NHC with respective iminoborane precursors RER yet occurs at ambient temperature to yield the ring-expanded products. When a less bulky iminoborane is brought in contact with sterically unhindered NHC neither the iminoborane dihydride is stable at room temperature nor is the RER observed to take place upon heating. The conversions of iminoboranes with very bulky NHC do not show BDF at ambient temperature and only in the case of the less hindered borane precursor the RER is found to proceed in a controlled fashion upon heating.

Reductive Ring-Expansion of 1-Bromoalkyl-2-Oxocycloalkanecarboxylates at Silver Cathodes

Free-radical ring-expansion reactions are useful for the synthesis of a variety of organic compounds; these reactions are especially attractive for the preparation of large rings in natural products.1 One such ring expansion, outlined by Dowd and Choi,2 employs tri-n-butyltin hydride in the presence of 2,2′-azobis(2-methylpropionitrile), commonly referred to as AIBN, to cleave a carbon–halogen bond and to induce ring expansion. These reagents are efficient, but are also environmentally dangerous. To remove the need for these harmful chemicals, our laboratory (which has a long-standing interest in the reductive cleavage of organic halides) has previously utilized glassy carbon cathodes to initiate reductive ring expansion and has obtained modest yields—up to 26%—of the ring-expanded product.3 More recently, it has been discovered that silver cathodes have a catalytic ability to cleave carbon–halogen bonds.4 In the present work, we have explored the use of silver cathodes for reductive ring-expansion reactions of the subject compounds, and we have been able to achieve higher yields of ring-expanded products at less negative potentials than previously found through the use of glassy carbon electrodes. Figure 1 shows a cyclic voltammogram for the reduction of methyl 1-(bromomethyl)-2-oxocyclopentanecarboxylate (1) at a silver cathode in dimethylformamide (DMF) containing tetramethylammonium tetrafluoroborate (TMABF4). We attribute the first cathodic peak at approximately –0.4 V to reductive cleavage of the carbon–bromine bond, whereas the second cathodic peak at –1.4 V is due to reduction of the cyclopentanone moiety. Interestingly, the first cathodic peak appears at a potential that is nearly 1 V more positive than that found with a glassy carbon electrode. Two other substrates—methyl 1-(bromopropyl)-2-oxocyclopentanecarboxylate (2) and ethyl 1-(bromomethyl)-2-oxocyclohexanecarboxylate (3)—that have been studied exhibit similar electrochemical behavior (Figure 2). Controlled-potential electrolyses have revealed that the electrochemically induced ring-expansion reaction occurs in a fashion similar to that of the original chemical reaction. We have observed a one-electron reduction of 1that affords the desired ring-expanded product in high yield—up to 95%. In addition to the ring-expanded product, side products (found by means of gas chromatography–mass-spectrometry) include a dehalogenated product and an unexpected side product that are shown in Figure 3. Yields of the various products obtained from the three substrates mentioned in the preceding paragraph depend on the length of the haloalkane side-chain and on the size of the ring.

Photofragmentation of Gas-Phase Lanthanide Cyclopentadienyl Complexes: Experimental and Time-Dependent Excited-State Molecular Dynamics.

Unimolecular gas-phase laser-photodissociation reaction mechanisms of open-shell lanthanide cyclopentadienyl complexes, Ln(Cp)3 and Ln(TMCp)3, are analyzed from experimental and computational perspectives. The most probable pathways for the photoreactions are inferred from photoionization time-of-flight mass spectrometry (PI-TOF-MS), which provides the sequence of reaction intermediates and the distribution of final products. Time-dependent excited-state molecular dynamics (TDESMD) calculations provide insight into the electronic mechanisms for the individual steps of the laser-driven photoreactions for Ln(Cp)3. Computational analysis correctly predicts several key reaction products as well as the observed branching between two reaction pathways: (1) ligand ejection and (2) ligand cracking. Simulations support our previous assertion that both reaction pathways are initiated via a ligand-to-metal charge-transfer (LMCT) process. For the more complex chemistry of the tetramethylcyclopentadienyl complexes Ln(TMCp)3, TMESMD is less tractable, but computational geometry optimization reveals the structures of intermediates deduced from PI-TOF-MS, including several classic “tuck-in” structures and products of Cp ring expansion. The results have important implications for metal–organic catalysis and laser-assisted metal–organic chemical vapor deposition (LCVD) of insulators with high dielectric constants.

A Concise Approach Toward Tetrazolyl-Substituted Benzazocines via a Novel Isocyanide-Based Multicomponent Reaction

The synthesis of pharmacologically relevant isoquinoline-tetrazoles and benzazocine-tetrazoles via sequential azido-Ugi and alkyne-induced ring-expansion reactions starting from cotarnine chloride are reported. A one-pot, multicomponent reaction protocol toward the ring-expanded product is also described.

ChemInform Abstract: Synthesis of Pyrrolo[1,2‐a][1,6]benzodiazonines from Pyrrolo[1,2‐a][1,4]benzodiazepines and Alkynes Containing Electron‐Acceptor Substituents.

AbstractReaction of pyrrolobenzodiazepines (I) with activated alkynes gives pyrrolo[1,2‐a][1,6]benzodiazonines as products of a diazepine ring expansion.

Near‐IR Absorbing Nickel(II) Porphyrinoids Prepared by Regioselective Insertion of Silylenes into Antiaromatic Nickel(II) Norcorrole

The treatment of an antiaromatic norcorrole Ni(II) complex with a kinetically stabilized silylene provided ring-expansion products in excellent yields through the highly regio- and stereoselective insertion into the β-β pyrrolic CC bonds. The resultant Ni(II) porphyrinoid monoinsertion product exhibited relatively strong near-IR absorption bands due to the small HOMO-LUMO gap in spite of the disrupted cyclic π-conjugation by the silicon atom.

ChemInform Abstract: Ring‐Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes Through Metal‐Catalyzed [1,2]‐Stevens Rearrangements.

Enantiopure binaphthyl azocines can be prepared in a single step via the direct copper-catalyzed reaction of binaphthyl azepines and α-diazo carbonyl reagents. The [1,2]-Stevens rearrangement is general (61–93% yields) and can be extended to [3]ferrocenophanes; similar reactivity in favor of the products of ring expansion is obtained with these ferrocene derivatives (80–96% yields).

Synthesis of pyrrolo[1,2-a][1,6]benzodiazonines from pyrrolo[1,2-a][1,4]benzodiazepines and alkynes containing electron-acceptor substituents

It has been established that the reaction of pyrrolo[1,2-a][1,4]benzodiazepines with activated alkynes gives pyrrolo[1,2-a][1,6]benzodiazonines as the products of diazepine ring expansion. In the case of pyrrolo[1,2-a][1,4]benzodiazepine, substituted with formyl group at the pyrrole ring, both expansion and cleavage of the diazepine fragment can occur.

Siloxane-bridged [n]troticenophanes: Syntheses, structures and ring-opening reactions

Salt elimination reactions between dilithiotroticene [(η7–C7H6Li)Ti(η5–C5H4Li)]∙pmdta (1) (pmdta = N,N′,N′,N″,N″-pentamethyldiethylenetriamine) and siloxane dichlorides ClMe2Si-(OSiMe2)m-Cl (m = 1–3) at low temperature allowed the synthesis and isolation of the siloxane-bridged [n]troticenophanes [(η7–C7H6)Ti(η5–C5H4)](OSiMe2)m(SiMe2) (2, m = 1; 3, m = 2; 4, m = 3) as blue crystalline solids in moderate yield. The compounds were characterized by 1H, 13C and 29Si NMR spectroscopy, elemental and single-crystal X-ray diffraction analyses. The molecular structures of 2 and 3 showed a low degree of strain indicated by the dihedral (α = 4.8° for 2; 4.9/3.7° for 3) and distortion (δ = 176.2° for 2; 174.3/176.3° for 3) angles between the two rings. The structure of 4 was severely disordered. Compounds 2–4 are thermally resistant to ring-opening polymerization, as revealed by differential scanning calorimetry studies, with 2 exhibiting the higher melting temperature. Moreover, the observation of two endotherms in the DSC spectrum of 2 suggests a solid state transition as a result of polymorphism. The reactions of 2–4 with basic initiators such as potassium siloxanolate, ammonium siloxanolate or n-BuLi and analysis of the product distribution by electron ionization mass spectrometry revealed the formation of oligotroticenylsiloxanes incorporating one or more troticenyl units, ring-opened troticenes and ring-expanded troticenophanes [(η7–C7H6)Ti(η5–C5H4)](OSiMe2)r(SiMe2) (r > m). Similar cleavage and extension of the ring were observed by treatment of 2–4 with the acidic initiator Purolite CT-175, and ring-opened troticenes having mixed terminal –OH and –SiMe3 groups were detected. Attempts to copolymerize 2–4 and cyclotrisiloxane with n-BuLi afforded essentially the monomeric and polymeric siloxanes [Me2SiO]w (w = 7, 8), Me2(nBu)Si[OSiMe2]yOSiMe2 (y = 3–6) and Me2(n-Bu)Si[OSiMe2]zOH (z = 1–7), together with the ring-opened and ring-expanded products mentioned above.

SYNTHESIS OF PYRROLO[1,2- a ][1,6]BENZODIAZONINES FROM PYRROLO[1,2- a ][1,4]BENZODIAZEPINES AND ALKYNES CONTAINING ELECTRON-ACCEPTOR SUBSTITUENTS

It has been established that the reaction of pyrrolo[1,2-a][1,4]benzodiazepines with activated alkynes gives pyrrolo[1,2-a][1,6]benzodiazonines as the products of diazepine ring expansion. In the case of pyrrolo[1,2-a][1,4]benzodiazepine, substituted with formyl group at the pyrrole ring, both expansion and cleavage of the diazepine fragment can occur. Authors: L. G. Voskressensky, T. N. Borisova, M. I. Babakhanov, T. M. Chervyakova, A. A. Titov, A. V. Butin, T. A. Nevolina, V. N. Khrustalev, and A. V. Varlamov. English Translation in Chemistry of Heterocyclic Compounds , 2013, 49 (7), pp 1024-1032 http://link.springer.com/article/10.1007/s10593-013-1340-z

Effect of water on product yields of 2-azidobenzoic acid photolysis in aprotic solvents

The effect of water admixtures on the formation of 2-oxo-(3H)-azepine-3-carboxylic acid and 2,1-benzisoxazol-3(1H)-one in the photolysis of 2-azidobenzoic acid in aprotic solvents has been investigated. It has been shown that the addition of nucleophilic agents to the reaction mixture determines the yields of not only 3H-azepines, the products of benzene ring expansion, but also the intramolecular cyclization product 2,1-benzisoxazol-3(1H)-one. Participation of the formed 2,1-benzisoxazol-3(1H)-one in the reaction has been suggested as an explanation of the effect of nucleophilic compounds (water, ethanol, and 2,1-benzisoxazol-3(1H)-one) on the product yield of the monomolecular reaction.

Ring-Expansion Reactions of Binaphthyl Azepines and Ferrocenophanes through Metal-Catalyzed [1,2]-Stevens Rearrangements

Enantiopure binaphthyl azocines can be prepared in a single step via the direct copper-catalyzed reaction of binaphthyl azepines and α-diazo carbonyl reagents. The [1,2]-Stevens rearrangement is general (61–93% yields) and can be extended to [3]ferrocenophanes; similar reactivity in favor of the products of ring expansion is obtained with these ferrocene derivatives (80–96% yields).

Ni/SiO<SUB>2</SUB> Catalyst for the Selective Ring Opening of Methylcyclopentane

The selective ring opening (SRO) of methylcyclopentane (MCP) catalyzed by 60 wt.% Ni/SiO2 has been studied. The highly loaded and well dispersed Ni/SiO2 catalyst was prepared by coprecipitation method and their surface characteristics were evaluated through H2-TPR, NH3-TPD, H2-chemisorption, XRD, SEM and TEM. The effect of different reaction temperature, H2 pressure, and WHSV on SRO of MCP was also investigated in the vapor phase reactor. The SRO of MCP produces n-hexane (n-H), 2-methylpentane (2-MP) and 3-methylpentane (3-MP) as desired RO products for the improvement of cetane number (CN) in fuel, along with some side products, such as cyclohexane as well as C1–C5 fragments as a ring enlargement (RE) and cracking (CR) products, respectively. Ni/SiO2 catalyst showed an unprecedented high catalytic performance with conversion 68.5% and 81.6% of RO products selectivity.

Reaction of 1,2‐Dialkyldiaziridines and 1,2,3‐Trialkyldiaziridines with Methyl Propiolate in Ionic Liquids and in Organic Solvents

An interaction of 1,2‐dialkyldiaziridine and 1,2,3‐trialkyldiaziridine with methyl propiolate was studied both in organic solvent (MeCN, CH2Cl2, C6H6) and in ionic liquids. Earlier unknown linear structures, in which three molecules of methyl propiolate were suited to one diaziridine molecule (adducts 1 : 3), were obtained in MeCN. The diaziridine ring expansion products 1,2,3,4‐tetrahydropyrimidine derivatives (adducts 1 : 2) and, along with them in some cases, the same linear structures were obtained in ionic liquids. A mechanism of reactions found was offered. The regioselectivity of reactions was supposed to determine by the structure of substituents in initial diaziridines. This conclusion was supported by quantum chemical calculations.

2,6-Diazasemibullvalenes: Synthesis, Structural Characterization, Reaction Chemistry, and Theoretical Analysis

A series of 2,6-diazasemibullvalenes (NSBVs) were synthesized and isolated from the reaction of 1,4-dilithio-1,3-dienes with nitriles via oxidant-induced C-N bond formation. For the first time, the activation barrier and an X-ray crystal structure of a substituted 2,6-diazasemibullvalene were determined. All NSBVs show extremely rapid aza-Cope rearrangement in solution, but the rapid aza-Cope rearrangement is "frozen" in the solid state, as shown by solid-state NMR measurements and X-ray single-crystal structural analysis. Insertion of unsaturated compounds or a low-valent metal center into the NSBV C-N bond gave diverse and interesting ring-expansion products. Theoretical analysis showed that the localized structure is predominant and that the homoaromatic delocalized structure exists as a minor component in the equilibrium.

ChemInform Abstract: Ring Enlargement versus Selenoetherification on the Reaction of Allenyl Oxindoles with Selenenylating Reagents.

AbstractTreatment of the allenyl oxindoles (I) with phenylselenium compounds results in formation of spirocyclic selenolactams and/or unexpected ring enlargement products like (III) and (IV).