Five-membered Ring Products Research Articles

Front Cover: Paddle‐Wheel Dirhodium Complexes Bearing Bulky Carboxylate Ligands: Synthesis and Catalysis in Carbene Insertion Reactions (Chem. Asian J. 11/2023)

Paddle-Wheel dirhodium complexes bearing bulky carboxylate ligands were synthesized and characterized. The steric bulk of carboxylate ligands could affect the reaction selectivity in Rh-catalyzed intramolecular competitive carbene insertions: Rh catalysts with bulky carboxylates could provide five-membered ring products preferentially via the insertion into a carbon–hydrogen bond while conventional Rh catalysts gave six-membered ring products via the insertion of a carbon-carbon double bond. More information can be found in the Research Article by Tetsuaki Fujihara et al.

Insight into the addition reactions of stannylenoid H2SnLiF with ethylene.

Tetrylenoids, R2EXM (E = Si, Ge, and Sn; X = electronegative group; M = alkali metal), have electrophilic and nucleophilic properties just like carbenoid. As the products of carbenoid compounds with olefins, the cyclopropane fraction has been found to be biologically active in many natural and artificial compounds. Can carbenoid analogues of stannylenoid facilitate similar cyclopropanation reactions? Addition reaction of the stannylenoid compound H2SnLiF with ethylene was investigated using density function theory (DFT) at the M062X/def2-TZVP level. The single-point energy calculations were performed on the basis of QCISD/def2-TZVP level. Two possible pathways were found for the addition reaction of H2SnLiF (R1) with ethylene (R2). The most favorable path is the two successive reactions of H2SnLiF and ethylene through the ternary ring product c-H2Sn(CH2)2 (P1) and then the formation of the five-membered ring product (P2). Solvation-related studies have shown that addition reactions are more likely to occur in the presence of THF solvents. This work provides theoretical support for the reactions of stannylenoid with olefins.

Paddle-Wheel Dirhodium Complexes Bearing Bulky Carboxylate Ligands: Synthesis and Catalysis in Carbene Insertion Reactions.

Dirhodium complexes bearing bulky carboxylate ligands are synthesized and characterized. The steric bulk of carboxylate ligands could affect the reaction selectivity in Rh-catalyzed intramolecular reactions: Rh catalysts with bulky carboxylate ligands provided five-membered ring products preferentially via the insertion into a carbon-hydrogen bond. Meanwhile, six-membered ring products were obtained using conventional Rh catalysts via the insertion of a carbon-carbon double bond.

An Alkyne-Isocyanide Cycloaddition/Boulton-Katritzky Rearrangement/Ring Expansion Reaction: Access to 9-Deazaguanines.

An alkyne-isocyanide [3 + 2] cycloaddition followed by a Boulton-Katritzky rearrangement and a ring expansion is demonstrated. Different from the typical Boulton-Katritzky rearrangement, which forms five-membered ring products, the rearrangement-ring expansion method provides a mild, efficient, and atom-economical access to fused 9-deazaguanine structures in high yields.

Mechanistic Study on Palladium-Catalyzed Cycloaddition of Vinylethylene Carbonates with α,β-Unsaturated Imines

Vinylethylene carbonates (VECs) have been a versatile synthon for the construction of cyclic oxygenates with a medium-sized ring structure. Zhao’s group first demonstrated the potential of VECs as 1,5-dipoles in medium-sized ring synthesis. In their study, (5 + 4) cyclization between VECs (R1 = Ph) and N-tosyl azadienes occurs predominantly under the catalysis of Pd2(dba)3·CHCl3/dppbz. By contrast, when unsubstituted VECs (R1 = H) were used, the five-membered ring product of (3 + 2) cycloaddition was yielded dominantly. We elucidated the key role of the regioselectivity via the mechanistic study of VEC-participated (3 + 2) and (5 + 4) cycloadditions with DFT calculations. The results indicate that the VEC moiety is close to the α,β-unsaturated imine moiety in the (3 + 2) cycloaddition transition state, and the phenyl group deviates from the conjugation plane and thus results in the higher distortion energy. In the presence of the unsubstituted VEC substrate, the steric hindrance in the (3 + 2) transition state is greatly reduced. Meanwhile, the formation of the five-membered ring is facilitated by the entropic effect, and thus, (3 + 2) dominates over the (5 + 4) cycloaddition in this case.

Dichotomy of platinum(II) and gold(III) carbene intermediates switching from N- to O-selectivity

Pt(II) and Au(III)-mediated intermolecular divergent annulations of benzofurazans and ynamides highlighted the N- to O-selectivity of tunable metal carbene intermediates. PtCl2 with a bulky phosphite ligand resulted in the specific synthesis of six-membered quinoxaline N-oxides and successfully suppressed the in-situ deoxygenation of N-oxides. On the other hand, an unique gold(III) catalyst (2,6-di-MeO-PyrAuCl3) led to the five-membered ring products, benzimidazoles. A broad scope of functional groups was well compatible, delivering better yields and selectivities in contrast to conventional gold(I) catalysts. The different behavior of presumed platinum(II) and gold(III) carbenes with respect to chemoselectivity was intensively examined by experiments and DFT calculations. A detailed mechanistic study, based on DFT calculations, revealed that the highly electrophilic carbocation-like gold(III) carbene triggers an oxophilic cyclization, followed by a cascade ring contraction and acyl migration. On the contrary, the Pt carbene species is less cationic, favoring the formation of the six-membered ring via N-attack.

Mechanism of Rhodium(III)-Catalyzed C-H Activation/Annulation of Aromatic Amide with α-Allenol: A Computational Study.

With the help of DFT calculations, the reaction mechanisms of the rhodium(III)-catalyzed C-H activation/annulation between aromatic amide and α-allenol leading to the formation of isoindolinone have been theoretically investigated. Our calculated results show that the catalytic cycle consists of four stages: N-H deprotonation and C-H activation (Stage I), allene insertion, rearrangement and isomerization (Stage II), β-H elimination and enol-keto tautomerism (Stage III), and catalyst regeneration resulting in the five-membered ring product (Stage IV). For stage IV, besides the reaction paths proposed by the experimentalists, i.e., the insertion and reductive elimination (labeled as path a) and the reductive elimination and hydroamination (labeled as path b), an alternative path which involves C-N and C-H reductive eliminations (labeled as path c) was proposed and examined. The computational results show that the newly established path c is more energetically favorable than the reaction paths proposed by the experimentalists (paths a and b). The allene (non-terminal double bond) insertion step contributes to the rate-determining step with an overall activation free energy of 24.6 kcal/mol. Our study is beneficial for a better comprehension of the reaction mechanisms and provides a significant suggestion for further development of similar reactions.

Prediction on the Origin of Selectivities in Base-controlled Switchable NHC-catalyzed Transformations.

The base-controlled mechanisms for N-heterocyclic carbene (NHC)-catalyzed divergent [3+3] and [3+2] annulation reactions were examined by using the DFT method. The reaction initiates with the complexation of NHC and enal to give the Breslow intermediate, which diverges afterward. Then, the azomethine imine can either react with the Breslow intermediate to give the six-membered ring product or the β-carbon protonation occurs for forming the enolate intermediate controlled by different bases. The formed enolate intermediate reacts with azomethine imine to afford the five-membered ring product. The calculated results show that only the base K2 CO3 can facilitate the structural transformation between homoenolate and enolate to switch the chemoselectivity; therefore, the [3+3] annulation happens preferentially in the presence of base DBU while the other situation occurs with K2 CO3 as base. The NCI analysis results reveal that the stereoselectivity is predominately determined by the π⋅⋅⋅π, C-H⋅⋅⋅O, and C-H⋅⋅⋅N interactions. The obtained mechanistic insights should provide valuable clues for the rational design of these kinds of divergent reactions.

Platinum-catalyzed reactions of 3,4-bis(dimethylsilyl)- and 2,3,4,5-tetrakis(dimethylsilyl)thiophene with alkynes and alkenes

The reactions of 3,4-bis(dimethylsilyl)thiophene (1) and 2,3,4,5-tetrakis(dimethylsilyl)thiophene (17) with alkynes and alkenes have been reported. The reactions of 1 with alkynes such as diphenylacetylene, 3-hexyne, phenyltrimethylsilylacetylene, and trimethylsilylacetylene, in the presence of a catalytic amount of tetrakis(triphenylphosphine)platinum(0) at 80 °C gave the [1,4]disilino[2,3-c]thiophene derivatives. With alkenes under the same conditions, 1 afforded the five-membered ring products, in addition to hydrosilylation products. Treatment of 2,3,4,5-tetrakis(dimethylsilyl)thiophene (17) with diphenylacetylene and styrene gave the respective dehydrogenative double silylation products, arising from 2 equivalents of the alkyne and alkene, and compound 17.

Corrigendum: Catalytic Desymmetrizing Dehydrogenation of 4-Substituted Cyclohexanones through Enamine Oxidation.

In Scheme 2 b of this Communication, derivatization product 5 d was reported to be a five-membered ring product. During recent investigations, the authors found that the structure of 5 d was incorrectly assigned. This error was caused by incorrect analysis of the NMR spectra. In a structural revision this compound was determined to be a four-membered ring product. A detailed analysis employing 2D NMR spectroscopy is provided in the Supporting Information accompanying this Corrigendum. This correction does not affect the results and conclusions in other parts of the Communication. The authors thank Prof. Josep Bonjoch for drawing their attention to this issue and they sincerely apologize for this mistake. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Mechanism insights into the oxidative degradation of decabromodiphenyl ethane by potassium permanganate in acidic conditions

The KMnO4 degradation of decabromodiphenyl ethane (DBDPE), an additive in brominated flame retardants (BFRs), was investigated in a sulfuric acid system. The degradation tests showed that DBDPE reacted completely with KMnO4 in sulfuric acid, and a removal rate of 99.71% seems realistic. Many products were detected by liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-Q-TOF-MS) analysis and gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) analysis. The degradation initially forms 1,2-bis(perbromophenyl)ethane-1,2-dione (P1), pentabromophenol (P2), 2-(perbromophenyl)ethanol (P3) and pentabromobenzoic acid (P28), and the subsequent transformation of these primary intermediates generates ring-opening, five-membered ring and six-membered heterocycle products over time. Two main reaction pathways involving the direct oxidation of the C–C bond of the ethyl group and the cleavage of the C–C bond between ethyl carbon and the adjacent carbon were proposed, and were further confirmed by point charges analyses and Wiberg bond order calculations. Furthermore, the toxicity of DBDPE and its degradation products were evaluated using the ECOSAR program. DBDPE was found to be a toxic substance that could cause great damage to three kinds of organisms in different trophic levels, while all the transformation products were less toxic than parent compound.

How the Coordinated Structures of Ag(I) Catalysts Affect the Outcomes of Carbon Dioxide Incorporation into Propargylic Amine: A DFT Study.

Density functional theory calculations have been carried out to explore the detailed mechanisms for carbon dioxide incorporation of N-unsubstituted propargylic amine catalyzed by Ag(I) catalysts. We show that the reaction undergoes substrate adsorption or displacement, isomerization from amine-coordinated species to the alkyne-coordinated species, CO2 attack, and proton transfer, giving the carbamate intermediate. Subsequently, the reaction would bifurcate at the intermolecular ring-closing step, which produces five-membered ring (5MR) and six-membered ring (6MR) products at the same time, thus raising a regioselectivity issue. Our calculations reveal that the outcomes of the reaction critically depend on the coordination number and the basicity of the ligands. Higher coordinate number and stronger basicity of the ligands would stabilize the 5MR transition state over the 6MR counterpart. Such a preference can be rationalized by using transition state energy decomposition. All of these results could promote the rational design of noble metal/organic base combined catalysts with higher selectivity.

Application of the Five-Membered Ring Ruthenium Products of Cyclometalation Reactions for Manufacturing Dye-Sensitized Solar Cells

Five-membered ring products of cyclometalation reactions are utilized as dyesensitizers for manufacturing very stable dye-sensitized solar cells. Such solar cells have greater stability than standard chelate-type N719 solar cells because the cyclometalated ligands in the five-membered ring products are stronger donors than the thiocyanate groups in the standard type. Solar cells with high overall energy conversion efficiencies are manufactured primarily by using three types of cyclometalated five-membered-ring ruthenium compounds: 1. A solar cell prepared with a phenylpyridine ruthenium compound, e.g., bis(4,4'-dicarboxy- 2,2'-bipyridine) 2-(2,4-difluorophenyl)pyridine ruthenium, shows an overall energy conversion efficiency of 10.1 %. 2. A solar cell with the ruthenium compound with 2,2’-bipyridine bearing two carboxyl ligands and two alkylthienothophene ligands and 2,3’-bipyridine bearing two alkyloxy ligands shows a high overall energy conversion efficiency with 9.4 % with the cobalt electrolyte [Co(phen)3]3+/2+. 3. A solar cell using a clometalated CNN tridentate ruthenium compound bearing an electron-donating substituent of a terminal substituent placed para to the triphenylamine achieves a high overall solar-to-electric energy conversion efficiency of 8.02 %. This result is almost the same as that of N3 under the same conditions. Keywords: Dye-sensitized solar cells, cyclometalation reactions, five-membered ring, ruthenium, photosensitizers.

Density functional theory investigation of the ruthenium-catalyzed cycloisomerization of silicon-tethered 1,7-enynes

Density functional theory calculations at the M06-2X/6-31G(d,p) (RECPs for Ru) level of theory are performed to explore the reaction mechanism for the cycloisomerization of silicon-tethered 1,7-enynes using CpRuCl as a catalyst. The solvent effect is taken into account by M06-2X/6-311++G (d,p) single-point calculations with SMD solvation model in toluene. The calculation results indicate that the reactions of the ruthenium-catalyzed cycloisomerization of 1,7-enynes occur through the possible mechanisms and get five-membered ring or six-membered ring products, respectively. The process of forming six-membered ring product is more favored kinetically with the barrier of 13.6kcal/mol for Ph group, while the energy barrier for five-membered ring product becomes relatively higher of 34.3kcal/mol. The above reaction mechanism indicates that the ruthenium-catalyzed cycloisomerization of silicon connected 1,7-enynes has high regioselectivity, which is consistent with the experimental observations of Kaminsky and Clark.

Carbon Dioxide Utilization by the Five-Membered Ring Products of Cyclometalation Reactions.

In carbon dioxide utilization by cyclometalated five-membered ring products, the following compounds are used in four types of applications:1. 2-Phenylpyrazole iridium compounds, pincer phosphine iridium compounds and 2-phenylimidazoline iridium compounds are used as catalysts for both formic acid production from CO2 and H2, and hydrogen production from the formic acid. This formic acid can be a useful agent for H2 production and storage for fuel cell electric vehicles.2. Other chemicals, e.g., dimethyl carbonate, methane, methanol and CO, are produced with dimethylaminomethylphenyltin compounds, pincer phosphine iridium compounds, pincer phosphine nickel compound and ruthenium carbene compound or 2-phenylpyridine iridium compounds, and phenylbenzothiazole iridium compounds as the catalysts for the reactions with CO2.3. The five-membered ring intermediates of cyclometalation reactions with the conventional substrates react with carbon dioxide to afford their many types of carboxylic acid derivatives.4. Carbon dioxide is easily immobilized at room temperature with immobilizing agents such as pincer phosphine nickel compounds, pincer phosphine palladium compounds, pincer N,N-dimethylaminomethyltin compounds and tris(2-pyridylthio)methane zinc compounds.

Applications of Cyclometalation Five-Membered Ring Products and Intermediates as Catalytic Agents

The five-membered ring products and intermediates of cyclometalation reactions are very easily synthesized via donation from a hetero atom to a metal atom, which leads to the very high functionality of the product. This functionality is caused by the donation of the hetero atom and various types of metal atoms, halogen atom and other ligands such as alkanes, alkenes, alkynes, Cp, Cp*, aryl groups and heterocyclic compounds. These products have three types of catalytic applications: cyclometalation five-membered ring products as catalysts, cyclometalation five-membered ring intermediates as catalyst agents and cyclometalation five-membered ring intermediates with unconventional substrates and as catalyst actions. Because of the high functionality of these products, the applications of them have been increasing not only as the metathesis in the first and second generations of Hoveyda-Grubbs catalysts but also as in chiral reactions, cross-coupling reactions and polymerization reactions. The above cyclometalation products have been utilized for the production in many industrial fields such as pharmaceuticals, OLEDs, carbon dioxide utilizations, dye-sensitizer solar cells and sensors. We expect that these products would be used for the development of further new industrial products.

ChemInform Abstract: Applications of Five‐Membered Ring Products of Cyclometalation Reactions as Anticancer Agents

AbstractReview: 51 refs.

Origins of the Regioselectivity in the Lutetium Triflate Catalyzed Ketalization of Acetone with Glycerol: A DFT Study

We describe DFT computations that address the regioselective preference toward the five-membered ring product 1,3-dioxolane (solketal) over the six-membered-ring product (1,3-dioxane) during Lu(OTf)3-catalyzed ketalization of acetone with glycerol. When ketalization occurs via the internal (secondary) −OH group of glycerol, only solketal production should be possible due to the symmetry of the intermediates. Ketalization via the terminal −OH group of glycerol is predicted to occur in a different manner than the conventionally proposed ketalization mechanism. A constrained hemiketal intermediate is invoked to explain the selectivity for solketal formation.

Pd/C–Cu mediated direct and one-pot synthesis of γ-ylidene butenolides

10% Pd/C in combination with CuI, PPh3, and Et3N has been identified as an effective catalyst system for the coupling of (Z)-3-iodoacrylic acid with terminal alkynes in 1,4-dioxane leading to the one-pot synthesis of γ-ylidene butenolides. The methodology showed remarkable regio- and stereoselectivity as only the five-membered lactone ring products were formed with an exocyclic double bond possessing Z-geometry.

Reaction of N-Heterocyclic Silylenes with Thioketone: Formation of Silicon-Sulfur Three (Si-C-S)- and Five (Si-C-C-C-S)-Membered Ring Systems

Three- and five-membered rings that bear the (Si-C-S) and (Si-C-C-C-S) unit have been synthesized by the reactions of LSiCl (1; L=PhC(NtBu)2 ) and L'Si (2; L'=CH{(CCH2 )(CMe)(2,6-iPr2 C6 H3 N)2 }) with the thioketone 4,4'-bis(dimethylamino)thiobenzophenone. Treatment of 4,4'-bis(dimethylamino)thiobenzophenone with LSiCl at room temperature furnished the [1+2]-cycloaddition product silathiacyclopropane 3. However, reaction of 4,4'-bis(dimethylamino)thiobenzophenone with L'Si at low temperature afforded a [1+4]-cycloaddition to yield the five-membered ring product 4. Compounds 3 and 4 were characterized by NMR spectroscopy, EIMS, and elemental analysis. The molecular structures of 3 and 4 were unambiguously established by single-crystal X-ray structural analysis. The room-temperature reaction of 4,4'-bis(dimethylamino)thiobenzophenone with L'Si resulted in products 4 and 5, in which 4 is the dearomatized product and 5 is formed under the 1,3-migration of a hydrogen atom from the aromatic phenyl ring to the carbon atom of the CS unit. Furthermore, the optimized structures of probable products were investigated by using DFT calculations.