Terminal Epoxides Research Articles

Facile Amberlyst A-21 catalyzed access of β-hydroxynitriles via epoxide opening in water

β-Hydroxynitriles are essential intermediates in the synthesis of diverse bioactive compounds and clinical drugs. One of the precursor reactions to these intermediates is the opening of an epoxide ring with a cyanide nucleophile. In the present study, we report a milder and safer route to β-hydroxynitriles employing recyclable, Amberlyst A-21 resin in the ring-opening of epoxides with acetone cyanohydrin in water. A diverse range of substrates (fifteen), including aromatic epoxides, phenoxy epoxides, non-terminal, and terminal aliphatic epoxides, are investigated under the optimized conditions to afford the desired β-hydroxynitriles in good to excellent yield. In addition to this, the recyclability of the Amberlyst A-21 resin is also successfully demonstrated. This relatively safer methodology has the potential to be explored in other organic transformations.

Base-mediated synthesis of benzimidazole-fused 1,4-benzoxazepines via sequential intermolecular epoxide ring-opening/intramolecular SNAr reactions

We have developed a transition-metal-free, practical route to benzimidazole-fused 1,4-benzoxazepines. Operationally, the protocol involves a K2CO3-mediated intermolecular ring opening of terminal epoxides by 2-(2-fluorophenyl)benzimidazole, followed by an intramolecular nucleophilic aromatic substitution (SNAr) reaction of the resulting products in the presence of NaH. We have also achieved an 11-step synthesis of a chroman-linked benzimidazole-fused 1,4-benzoxazepine using a phenoxide-ion induced 6-exo intramolecular epoxide ring-opening and an alkoxide-ion induced intramolecular SNAr reaction as key steps.

Choline-based eutectic mixtures as catalysts for effective synthesis of cyclic carbonates from epoxides and CO2

• Choline salts have been mixed with hydrogen bond donors to form eutectic mixtures. • Choline-based eutectic mixtures catalyze CO 2 conversion to cyclic carbonates. • Carbonatation run in mild condition of temperature (80 °C) and pressure (0.1–0.4 MPa). • Good to very good yields are obtained on various terminal epoxides. • The eutectic catalysts are bio-based, non-toxic, recyclable and easily synthesized. CO 2 is a renewable, abundant and cheap C1-feedstock and its conversion to cyclic carbonates starting from epoxides has been widely explored in the last years. Nevertheless, conducting this reaction under mild and sustainable conditions is still a challenging task. Herein we present the use of choline-salt based eutectic mixtures as catalysts for the reaction of CO 2 with epoxides to give cyclic carbonates. Choline chloride and choline iodide have been coupled with various hydrogen bond donors (HBDs), mainly cheap and bio-based carboxylic acids and polyols, to form two classes of eutectic mixtures. Very good yields were achieved under mild conditions (80 °C in 7–22 h) for various terminal epoxides, with both classes of catalysts. While a pressure of 0.4 MPa of CO 2 is required to obtain appreciable conversions using choline chloride-based mixture, atmospheric pressure of CO 2 (balloon) has been successfully used with choline iodide-based mixtures. Furthermore, the catalysts could be recycled without appreciable loss of the catalytic activity. The improved catalytic performance of both choline-based eutectic mixtures is attributed to the synergistic activity of the halide, responsible for the opening of the epoxy-ring, and the HBD that has a role in the stabilization of the alkoxide intermediate.

Epoxidation of Cardanol's Terminal Double Bond.

In this investigation, the terminal double bonds of the side chain epoxidized cardanol glycidyl ether (SCECGE) molecule were further epoxidized in the presence of Oxone® (potassium peroxomonosulfate) and fluorinated acetone. Regular methods for the double bond epoxidation are not effective on the terminal double bonds because of their reduced electronegativity with respect to internal double bonds. The terminal double bond functionality of the SCECGE was epoxidized to nearly 70%, increasing the epoxy functionality of SCECGE from 2.45 to 2.65 epoxies/molecule as measured using proton magnetic nuclear resonance (1H-NMR). This modified material—side chain epoxidized cardanol glycidyl ether with terminal epoxies (TE-SCECGE)—was thermally cured with cycloaliphatic curing agent 4-4′-methylenebis(cyclohexanamine) (PACM) at stoichiometry, and the cured polymer properties, such as glass transition temperature (Tg) and tensile modulus, were compared with SCECGE resin cured with PACM. The Tg of the material was increased from 52 to 69 °C as obtained via a dynamic mechanical analysis (DMA) while the tensile modulus of the material increased from 0.88 to 1.24 GPa as a result of terminal double bond epoxidation. In addition to highlighting the effects of dangling side groups in an epoxy network, this modest increase in Tg and modulus could be sufficient to significantly expand the potential uses of amine-cured cardanol-based epoxies for fiber reinforced composite applications.

Enhanced carbon dioxide conversion at ambient conditions via a pore enrichment effect

Chemical fixation of carbon dioxide (CO2) may be a pathway to retard the current trend of rapid global warming. However, the current economic cost of chemical fixation remains high because the chemical fixation of CO2 usually requires high temperature or high pressure. The rational design of an efficient catalyst that works at ambient conditions might substantially reduce the economic cost of fixation. Here, we report the rational design of covalent organic frameworks (COFs) as efficient CO2 fixation catalysts under ambient conditions based on the finding of “pore enrichment”, which is concluded by a detailed investigation of the 10994 COFs. The best predicted COF, Zn-Salen-COF-SDU113, is synthesized, and its efficient catalytic performance for CO2 cycloaddition to terminal epoxide is confirmed with a yield of 98.2% and turnover number (TON) of 3068.9 under ambient conditions, which is comparable to the reported leading catalysts. Moreover, this COF achieves the cycloaddition of CO2 to 2,3-epoxybutane under ambient conditions among all porous materials. This work provides a strategy for designing porous catalysts in the economic fixation of carbon dioxide.

A Phosphonium Ylide as a Ligand for [3 + 2] Coupling Reactions of Epoxides with Heterocumulenes under Mild Conditions.

The potential of carbonyl-stabilized phosphonium ylides as ligands for novel catalysis was explored. We found that the combination of phosphonium ylides and metal halide salts efficiently catalyzed the reaction of epoxides with carbon dioxide under mild conditions. Five-membered cyclic carbonates, including disubstituted cyclic carbonates, were obtained in good yields with the use of 1 atm of carbon dioxide at 35 °C. Terminal epoxides could be converted to N-aryl oxazolidinones in the reaction with isocyanates under a similar catalytic system.

Deoxygenation of Epoxides with Carbon Monoxide.

The use of carbon monoxide as a direct reducing agent for the deoxygenation of terminal and internal epoxides to the respective olefins is presented. This reaction is homogeneously catalyzed by a carbonyl pincer‐iridium(I) complex in combination with a Lewis acid co‐catalyst to achieve a pre‐activation of the epoxide substrate, as well as the elimination of CO2 from a γ‐2‐iridabutyrolactone intermediate. Especially terminal alkyl epoxides react smoothly and without significant isomerization to the internal olefins under CO atmosphere in benzene or toluene at 80–120 °C. Detailed investigations reveal a substrate‐dependent change in the mechanism for the epoxide C−O bond activation between an oxidative addition under retention of the configuration and an SN2 reaction that leads to an inversion of the configuration.

Ligand-Free Nickel-Catalyzed Reductive Allylic Defluorinative Cross-Coupling of α-Trifluoromethyl Alkenes with Epoxides

We report a reductive allylic defluorinative reaction of α-trifluoromethyl alkenes with terminal epoxides, which consists of an iodide-mediated regioselective ring opening and a nickel-catalyzed radical-type cross-coupling, providing diverse tertiary gem-difluorobishomoallylic alcohols in moderate to high yields. Notably, this reaction is conducted under mild conditions and requires no external ligand or proton donor.

Enantioselective terpolymerization of racemic and meso-epoxides with anhydrides for preparation of chiral polyesters

The preparation of stereochemistry- and sequence-defined polymers, in which different monomer units are arranged in an ordered fashion just like biopolymers, is of great interest and has been a long-standing goal for chemists due to the expectation of unique macroscopic properties. Here, we describe the enantioselective terpolymerization of racemic terminal epoxides, meso-epoxides, and anhydrides mediated by the privileged chiral dinuclear Al(III) catalyst system, to afford optically active polyester terpolymers with either gradient or random distribution as determined by the epoxides employed during their preparation. The enantioselective terpolymerization of racemic tert-butyl glycidyl ether (rac-TBGE) and cyclopentene oxide with phthalic anhydride (PA) or naphthyl anhydride (NA) gives novel gradient polyesters, in which the crystallization behavior varies continuously along the main chain, due to the decrement of one ester component and the increment of the other occurring sequentially from one chain end to the other. In contrast, the enantioselective terpolymerization of rac-TBGE and meso-epoxide (cyclohexene oxide, 3,4-epoxytetrahydrofuran, or 1,4-dihydronaphthalene oxide) with an anhydride (PA or NA) provided chiral statistical terpolyesters with the random distribution of two kinds of ester units, resulting in a material possessing a mixed glass transition temperature. The present study therefore provides a convenient route to chiral polyesters bearing a range of physical and degradability properties.

Catalytic Conversion of Carbon Dioxide Using Binuclear Double-Stranded Helicates: Cyclic Carbonate from Epoxides and Diol.

The construction of sophisticated molecular architectures from chemical subunits requires careful selection of the spacers, precise synthetic strategies, and substantial efforts. Here, we report a series of binuclear double-stranded helicates synthesized from different combinations of pyridyl hydrazone-based multidentate ligands (H21, H22, H23) by increasing the methylene spacer and transition metals (Co, Ni, and Zn). The ligands H21 (N′1,N′3-bis((E)-pyridin-2-ylmethylene)malonohydrazide), H22 (N′1,N′4-bis((E)-pyridin-2-ylmethylene)succinohydrazide), and H23 (N′1,N′5-bis((E)-pyridin-2-ylmethylene)glutarohydrazide) and their respective complexes with Co, Ni, and Zn were obtained. Single-crystal X-ray diffraction studies of these binuclear metallohelicates confirm the double-stranded helical structure of the complexes derived from H22. The set of helicates Co-1, Co-2, and Co-3; Ni-1, Ni-2, and Ni-3; and Zn-1, Zn-2, and Zn-3 were investigated for its catalytic activity in the cyclic carbonate formation reaction. Intriguingly, among the synthesized catalyst, Co-1 was found to be better in terms of conversions with the calculated TOF (turnover frequency) of 128/h. The catalytic performance was significantly improved by adding 0.2 mmol of tetrabutylammonium bromide by achieving 76% conversion in 30 min, with the observed TOF of 15,934 h–1/molecule and 7967 h–1/Co center. The results obtained herein show that the double-stranded helicates are effective catalysts for converting both terminal and non-terminal epoxides into their corresponding cyclic carbonates. The striking feature of this catalytic protocol lies in demonstrating the catalytic activity for the conversion of diol to cyclic carbonate, and the detailed kinetic experiments tempted us to propose a tentative reaction mechanism for this conversion.

A General Regioselective Synthesis of Alcohols by Cobalt-Catalyzed Hydrogenation of Epoxides.

A straightforward methodology for the synthesis of anti‐Markovnikov‐type alcohols is presented. By using a specific cobalt triphos complex in the presence of Zn(OTf)2 as an additive, the hydrogenation of epoxides proceeds with high yields and selectivities. The described protocol shows a broad substrate scope, including multi‐substituted internal and terminal epoxides, as well as a good functional‐group tolerance. Various natural‐product derivatives, including steroids, terpenoids, and sesquiterpenoids, gave access to the corresponding alcohols in moderate‐to‐excellent yields.

A General Regioselective Synthesis of Alcohols by Cobalt‐Catalyzed Hydrogenation of Epoxides

AbstractA straightforward methodology for the synthesis of anti‐Markovnikov‐type alcohols is presented. By using a specific cobalt triphos complex in the presence of Zn(OTf)2 as an additive, the hydrogenation of epoxides proceeds with high yields and selectivities. The described protocol shows a broad substrate scope, including multi‐substituted internal and terminal epoxides, as well as a good functional‐group tolerance. Various natural‐product derivatives, including steroids, terpenoids, and sesquiterpenoids, gave access to the corresponding alcohols in moderate‐to‐excellent yields.

Green Pathway in Utilizing CO2 via Cycloaddition Reaction with Epoxide—A Mini Review

Carbon dioxide (CO2) has been anticipated as an ideal carbon building block for organic synthesis due to the noble properties of CO2, which are abundant renewable carbon feedstock, non-toxic nature, and contributing to a more sustainable use of resources. Several green and proficient routes have been established for chemical CO2 fixation. Among the prominent routes, this review epitomizes the reactions involving cycloaddition of epoxides with CO2 in producing cyclic carbonate. Cyclic carbonate has been widely used as a polar aprotic solvent, as an electrolyte in Li-ion batteries, and as precursors for various forms of chemical synthesis such as polycarbonates and polyurethanes. This review provides an overview in terms of the reaction mechanistic pathway and recent advances in the development of several classes of catalysts, including homogeneous organocatalysts (e.g., organic salt, ionic liquid, deep eutectic solvents), organometallic (e.g., mono-, bi-, and tri-metal salen complexes and non-salen complexes) and heterogeneous supported catalysts, and metal organic framework (MOF). Selection of effective catalysts for various epoxide substrates is very important in determining the cycloaddition operating condition. Under their catalytic systems, all classes of these catalysts, with regard to recent developments, can exhibit CO2 cycloaddition of terminal epoxide substrates at ambient temperatures and low CO2 pressure. Although highly desired conversion can be achieved for internal epoxide substrates, higher temperature and pressure are normally required. This includes fatty acid-derived terminal epoxides for oleochemical carbonate production. The production of fully renewable resources by employment of bio-based epoxy with biorefinery concept and potential enhancement of cycloaddition reactions are pointed out as well.

Regioselective Cross-Electrophile Coupling of Epoxides and (Hetero)aryl Iodides via Ni/Ti/Photoredox Catalysis.

A cross-electrophile coupling reaction of epoxides and (hetero)aryl iodides that operates via the merger of three catalytic cycles involving a Ni-, Ti-, and organic photoredox catalyst has been developed. Three distinct classes of epoxides, styrene oxides, cyclic epoxides, and terminal aliphatic epoxides, all undergo coupling in moderate to good yield and high regioselectivity with the use of three different nitrogen-based ligands for Ni under otherwise identical reaction conditions. The mild reaction conditions accommodate a broad scope of abundant and complex coupling partners. Mechanistic studies suggest that when styrene oxides are employed radical intermediates are involved via Ti-radical ring-opening of the epoxide. Conversely, for terminal aliphatic epoxides, involvement of an iodohydrin intermediate enables the formation of the unexpected linear product.

Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment.

We designed and synthesized a novel 1,2-deoxy-pyranose and terminal epoxide methyl substituted derivatives of spliceostatin A using Julia-Kocienski olefination as a key step. With respect to the biological activity, the 1,2-deoxy-pyranose analogue of spliceostatin A suppressed AR-V7 expression at the nano level (IC50 = 3.3 nM). In addition, the in vivo toxicity test showed that the 1,2-deoxy-pyranose analogue was able to avoid severe toxicity compared to spliceostatin A.

A Modified Synthesis of Oxetan-3-ol

A highly regioselective ring opening reaction of terminal epoxides with 2-bromobenzoic acid catalyzed by tetrabutylammonium bromide was accomplished. The procedure is operationally simple and practical for the synthesis of a series of β-hydroxy esters. Using this protocol, oxetan-3-ol could be prepared efficiently in a good yield.

Direct evidence for the validity of assessing reaction extent by torque spectrum during reactive processing

In this work, direct evidence for the validity of assessing reaction extent by torque spectrum during reactive processing has been provided by taking PVDF/PLLA/RCC (reactive comb-like compatibilizers) as an example. In RCC, three types of repeat units are found (in a perfectly random fashion) along the backbone, namely MMA units, unreacted GMA units and GMA units reacted with the MMA macromonomer (the latter represent the teeth of the comb). Upon blending, a percentage of PLLA is grafted onto RCC because of the reaction between its terminal carboxyl group and epoxide group in RCC. In the resultant co-continuous structures, extraction and acid hydrolysis have been employed to distinguish reacted and free (un-reacted) PLLA, in which only free PLLA and all (un-reacted and reacted) PLLA can be removed, producing extraction ratio (ER) and acid hydrolysis ratio (AR) respectively. The graft ratio (GR) of PLLA, calculated based on the difference between AR and ER, represents the reaction extent directly. The comparison of GR and torque indicates that they exhibit the same evolution with not only similar increase/equilibrium regimes but also comparable critical transition time. Therefore, our results confirm that torque spectrum can be used to describe the reaction extent as accurately as graft ratio, which is significant for the basic understanding and applications of reactive processing.

Luffa sponge supported dendritic imidazolium ILs with high-density active sites as highly efficient and environmentally friendly catalysts for CO2 chemical fixation

Efficient using of green heterogeneous catalysts from renewable natural sources through chemical modification for the cycloaddition of terminal epoxides with CO2 is attractive but still challenging. Luffa sponge is a cheap, biodegradable, abundant and renewable source with netting-like three-dimensional porous structure. Herein, we report a simple and facile approach to the preparation of a series of novel luffa sponge-supported dendritic imidazolium ILs heterogeneous catalysts LS-DIL-(G1-G3) with high ionic density from natural luffa sponge fibers. LS-DIL-(G1-G3) were properly characterized by FT-IR spectroscopy, TGA, elemental analysis, and SEM. Among them, LS-DIL-G3 was found to exhibit the highest catalytic activity for the synthesis of cyclic carbonates under metal-free and solvent-free conditions. It was clearly observed that there was a positive dendritic effect on the yields of cyclic carbonates. Furthermore, a wide range of terminal epoxides was converted smoothly to the corresponding cyclic carbonates with high yields (84–99 %). LS-DIL-G3 could be reused for up to six consecutive runs without any obvious decline in catalytic activity. Importantly, the desired cyclic carbonates could be prepared on a multigram scale by using LS-DIL-G3 as a green heterogeneous catalyst.

Lignin modified by deep eutectic solvents as green, reusable, and bio-based catalysts for efficient chemical fixation of CO2

Lignin is a biodegradable, abundant and renewable natural polymer on earth. In this study, deep eutectic solvents (DESs)-modified lignin heterogeneous catalysts were prepared for the first time via a facile acid-base interaction between choline chloride (ChCl) and p-aminobenzoic acid (PABA) or its derivatives, which were used to efficiently catalyze the cycloaddition of CO2 and terminal epoxides under green and mild conditions. Among them, lignin-ChCl-PABA was found to exhibit the highest catalytic activity for the cycloaddition of epoxides in the presence of 1.0 MPa of CO2 while retaining high selectivity, which far outperformed those achieved on the homogeneous EDSs catalytic system. A series of cyclic carbonates could be obtained in high yields (90–99%), and lignin-ChCl-PABA was stable and reusable for the cycloaddition reaction (84% yield after 5 recycles). The attaching DES of ChCl/PABA onto the functional lignin increased the catalytic activity and also made the catalyst easier to recycle from the reaction mixture. The OH and NH2 groups on the surface of lignin-ChCl-PABA played a very important role in the acceleration of the cycloaddition reaction under solvent free conditions.

Continuous Flow Synthesis of Terminal Epoxides from Ketones Using in Situ Generated Bromomethyl Lithium.

A scalable procedure for the direct preparation of epoxides from ketones has been developed. The method is based on the carefully controlled generation of (bromomethyl)lithium (LiCH2Br) from inexpensive CH2Br2 and MeLi in a continuous flow reactor. The reaction has shown excellent selectivity for a variety of substrates, including α-chloroketones, which typically fail under classic Corey-Chaykovsky conditions. This advantage has been used to develop a novel route toward the drug fluconazole.