Hyperbranched polyethers by ring‐opening polymerization: Contribution of activated monomer mechanism

Propagation in the cationic ring‐opening polymerization of cyclic ethers involves nucleophilic attack of oxygen atoms from the monomer molecules on the cationic growing species (oxonium ions). Such a mechanism is known as the active chain‐end mechanism. If hydroxyl groups containing compounds are present in the system, oxygen atoms of HO? groups may compete with cyclic ether oxygen atoms of monomer molecules in reaction with oxonium ions. At the proper conditions, this reaction may dominate, and propagation may proceed by the activated monomer mechanism, that is, by subsequent addition of protonated monomer molecules to HO? terminated macromolecules. Both mechanisms may contribute to the propagation in the cationic polymerization of monomers containing both functions (i.e., cyclic ether group and hydroxyl groups) within the same molecule. In this article, the mechanism of polymerization of three‐ and four‐membered cyclic ethers containing hydroxymethyl substituents is discussed in terms of competition between two possible mechanisms of propagation that governs the structure of the products—branched polyethers containing multiple terminal hydroxymethyl groups. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 457–468, 2003     

Hydrogen‐Bonding Catalyzed Ring‐Closing C−O/C−O Metathesis of Aliphatic Ethers over Ionic Liquid under Metal‐Free Conditions

O‐heterocycles have wide applications, and their efficient and green synthesis is very interesting. Herein, we report hydrogen‐bonding catalyzed ring‐closing metathesis of aliphatic ethers to O‐heterocycles over ionic liquid (IL) catalyst under metal‐ and solvent‐free conditions. The IL 1‐butylsulfonate‐3‐methylimidazolium trifluoromethanesulfonate ([SO₃H‐BMIm][OTf]) is discovered to show outstanding performance, better than the reported catalysts. An interface effect plays an important role in mediating the reaction rate due to the immiscibility between the products and the IL catalyst, and the products can be spontaneously separated. NMR analysis and DFT calculation suggest that a pair of cation and anion of [SO₃H‐BMIm][OTf] could form three strong H‐bonds with an ether molecule, which catalyze the ether transformation via a cyclic oxonium intermediate. A series of O‐heterocycles including tetrahydrofurans, tetrahydropyrans, morpholines and dioxane can be obtained from their corresponding ethers in excellent yields (e.g., >99 %). This work opens an efficient and metal‐free way to produce O‐heterocycles from aliphatic ethers.     

Reaction mechanisms of a cyclic ether intermediate: Ethyloxirane

Oxiranes are a class of cyclic ethers formed in abundance during low‐temperature combustion of hydrocarbons and biofuels, either via chain‐propagating steps that occur from unimolecular decomposition of β‐hydroperoxyalkyl radicals (β‐?QOOH) or from reactions of HO? with alkenes. Ethyloxirane is one of four alkyl‐substituted cyclic ether isomers produced as an intermediate from n‐butane oxidation. While rate coefficients for β‐?QOOH → ethyloxirane + ?H are reported extensively, subsequent reaction mechanisms of the cyclic ether are not. As a result, chemical kinetics mechanisms commonly adopt simplified chemistry to describe ethyloxirane consumption by convoluting several elementary reactions into a single step, which may introduce mechanism truncation error—uncertainty derived from missing or incomplete chemistry. The present work provides fundamental insight on reaction mechanisms of ethyloxirane in support of ongoing efforts to minimize mechanism truncation error. Reaction mechanisms are inferred from the detection of products during chlorine atom‐initiated oxidation experiments using multiplexed photoionization mass spectrometry conducted at 10 Torr and temperatures of 650 K and 800 K. To complement the experiments, calculations of stationary point energies were conducted using the ccCA‐PS3 composite method on ?R + O₂ potential energy surfaces for the four ethyloxiranyl radical isomers, which produced barrier heights for 24 reaction pathways. In addition to products from ?QOOH → cyclic ether + ?H and ?R + O₂ → conjugate alkene + HO?, both of which were significant pathways and are prototypical to alkane oxidation, other species were identified from ring‐opening of both ethyloxiranyl and ?QOOH radicals. The latter occurs when the unpaired electron is localized on the ether group, causing the initial ?QOOH structure to ring‐open and form a resonance‐stabilized ketohydroperoxide‐type radical. The present work provides the first analysis of ethyloxirane oxidation chemistry, which reveals that consumption pathways are complex and may require an expansion of submechanisms to increase the fidelity of chemical kinetics mechanisms.     

Magnesium Halide‐promoted Ring‐opening Reaction of Cyclic Ether in the Presence of Phosphine Halide

A new route to the direct preparation of H‐phosphinate esters has been explored. The ring‐opening reaction of cyclic ether (tetrahydrofuran or tetrahydropyrane) was carried out with magnesium halide in the presence of phosphine halide (PRCl₂ or PCl₃). The process is straightforward and all the reagents are relatively cheap and readily available. Magnesium halide‐mediated THF ring‐opening (S_N2@C) and the subsequent S_N2@P elementary reactions that giving rise to the intermediate of haloalkyl phosphinates have been discussed based on our experimental findings ( Path I : S_N2@C−+S_N2@P). Another possible route, the direct S_N2 between THF (nucleophile) and phosphine halide (electrophile) that followed by THF ring opening by halide dissociated from phosphine halide ( Path II: S_N2@P−+S_N2@C), was also proposed. However, path II is the least likely reaction path because neutral THF is not a good nucleophile. H‐phosphinate esters could be readily available in the subsequent hydrolysis process. Considering the ionic bond strength in magnesium halides and the nucleophilicity of halides dissociated from MgX₂ in protic solvents like water, MgBr₂ is recommended for ring‐opening reactions of cyclic ethers.     

Gold‐Catalyzed 1,2‐Acyloxy Migration/Intramolecular [3+2] 1,3‐Dipolar Cycloaddtion Cascade Reaction: An Efficient Strategy for Syntheses of Medium‐Sized‐Ring Ethers and Amines

A highly efficient strategy for the formation of medium‐sized‐ring ethers and amines based on a gold‐catalyzed cascade reaction, involving enynyl ester isomerization and intramolecular [3+2] cyclization, has been developed. Various multisubstituted medium‐sized‐ring unsaturated ethers and amines were obtained through this transformation. This method represents one of the relatively few transition metal catalyzed intramolecular cycloaddition reactions for medium‐sized ring synthesis.     

Catalytic Reduction of Cyclic Ethers with Hydrosilanes

Catalytic reductive transformations of ethers as a synthetic building block are an important class of chemical reactions because a range of essential chemical feedstocks and fuels in contemporary life can be prepared through the key step of ethereal C?O bond cleavage of cellulosic biomass. Although conventional stoichiometric and catalytic methods for sp²‐ and sp³‐C?O bond cleavage of linear ethers and alcohols with hydrosilanes are well established, silylative ring opening of cyclic ethers has been less highlighted in this context. This review outlines catalytic systems for the silylative reduction of a range of cyclic ethers, including epoxides and sugars, leading to the corresponding alcohols and/or hydrocarbons. The chemical reactivity and selectivity of these ring‐opening catalytic processes are discussed with respect to the type of substrates; the representative catalytic working modes are also described.     

Synthesis of Functionalized Medium‐Sized trans‐Cycloalkenes by 4π Electrocyclic Ring Opening/Alkylation Sequence

Development of a novel synthetic method for medium‐sized trans‐cycloalkenes (TCAs) is described. Functionalized TCAs are readily prepared from simple cycloalkanones in a few steps, namely, enol silyl ether formation, [2+2] cycloaddition, and domino 4π electrocyclic ring opening/alkylation (conjugate addition). The first example of central‐to‐planar chirality transfer from enantiomerically enriched cyclobutenes to TCAs is also described.     

Regioselective ring opening of unsymmetrical cyclic ethers with the A1C13-NaI-acetonitrile system: Application to hydroxylation of ent-kaurene.

Unsymmetrically substituted 5-membered cyclic ethers were effectively cleaved with the A1C1₃-NaI-CH₃CN system at the less hindered carbon atom to afford δ-iodoalcohols. Conversion of ent-kaurene to ent-14α- and ent-12β-hydroxykaurene was achieved through the ring opening of the cyclic ether with the present system as a key step.     

Cleavage of different ether bonds in butyl glycidyl ether and allyl glycidyl ether by K, K(15-crown-5)2

The kind of substituent in alkyl glycidyl ethers affects the course of their reaction with K⁻, K⁺(15-crown-5)₂. The cyclic oxirane ring is exclusively cleaved in the case of butyl glycidyl ether whereas the presence of the unsaturated allyl group in the glycidyl ether molecule unexpectedly prefers the scission of the linear ether bond. In both the systems organometallic intermediates are formed. They react with crown ether causing its ring opening. Allylpotassium formed from allyl glycidyl ether reacts also with another glycidyl ether molecule; the oxirane ring is opened in this case.     

Gold(I)‐Catalyzed Divergence in the Preparation of Bicyclic Enol Esters: From Exclusively [3C+2C]‐Cycloaddition Reactions to Exclusive Formation of Vinylcyclopropanes

With the use of benzonitrile‐stabilized Au^I catalyst [Au(IPr)(NCPh)]SbF₆ ( Ic ; IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene), a spectrum of reactivity is observed for propargyl ester 4 a with cyclic vinyl ethers, ranging from exclusively [3C+2C] cycloaddition reactions to exclusively cyclopropanation depending only on the structure of the substrate. Some initially formed cyclopropanation products rearrange into the corresponding formally [3C+2C] cycloaddition products after treatment with fresh Au^I complex at 80 °C. Vinylcyclopropanes formed from dihydrofuran and dihydropyran resisted such rearrangement, even in the presence of fresh Au^I catalyst at elevated temperature. This study addresses an important mechanistic question concerning whether the five‐membered‐ring products were produced by a direct [3C+2C] cycloaddition reaction or by a sequential cyclopropanation/ring‐expansion reaction. A dual pathway is proposed for the Au^I‐catalyzed reactions between propargyl esters and cyclic vinyl ethers. The different behavior among vinyl cyclic ethers is attributed to the difference in the polarization of the π bond. Highly polarized bonds appear to undergo the cycloaddition reaction whereas less polar π‐bonds produce cyclopropanes.     

A highly efficient iterative approach to fused ether ring systems

An iterative synthesis of fused ether ring systems has been developed. This strategy couples a cyclic enol ether oxidation and carbon-carbon bond forming reaction in one flask with an acid catalyzed cyclic acetal formation and alkoxide elimination in another flask. The result is a general and highly efficient two flask synthesis of fused ethers as are present in a wide variety of bioactive natural products.     

Alkylation of acetals using manganate-BF3·OEt2 mixed reagent

A mixture of `R<sub>3</sub>MnMgBr' and BF<sub>3</sub>·OEt<sub>2</sub> prepared in advance only by stirring both reagents in ether converted acetals to alkylation products, where an alkoxy group of acetals was substituted by the alkyl group of manganese reagent used. Ketals also reacted with the `mixed reagent' to afford the corresponding alkylation products in high yield. α-Alkoxy-substituted cyclic ethers and acetoxy-substituted cyclic ethers were selectively converted to ring-opening alkylation products and α-alkyl-substituted cyclic ethers, respectively.     

Isomer‐dependent reaction mechanisms of cyclic ether intermediates: cis‐2,3‐dimethyloxirane and trans‐2,3‐dimethyloxirane

Oxiranes are a class of cyclic ethers formed in abundance during low‐temperature combustion of hydrocarbons and biofuels, either via chain‐propagating steps that occur from unimolecular decomposition of β‐hydroperoxyalkyl radicals (β‐?QOOH) or from reactions of H?O with alkenes. The cis‐ and trans‐isomers of 2,3‐dimethyloxirane are intermediates of n‐butane oxidation, and while rate coefficients for β‐?QOOH → 2,3‐dimethyloxirane + ?OH are reported extensively, subsequent reaction mechanisms of the cyclic ethers are not. As a result, chemical kinetics mechanisms commonly adopt simplified chemistry to describe the consumption of 2,3‐dimethyloxirane by convoluting several elementary reactions into a single step, which may introduce mechanism truncation error—uncertainty derived from missing or incomplete chemistry. The present research examines the isomer dependence of 2,3‐dimethyloxirane reaction mechanisms in support of ongoing efforts to minimize mechanism truncation error. Reaction mechanisms are inferred via the detection of products from Cl‐initiated oxidation of both cis‐2,3‐dimethyloxirane and trans‐2,3‐dimethyloxirane using multiplexed photoionization mass spectrometry (MPIMS). The experiments were conducted at 10 Torr and temperatures of 650 K and 800 K. To complement the experiments, the enthalpies of stationary points on the ?R + O₂ surfaces were computed at the ccCA‐PS3 level of theory. In total, 28 barrier heights were computed on the 2,3‐dimethyloxiranylperoxy surfaces. Two notable aspects are low‐lying pathways that form resonance‐stabilized ketohydroperoxide‐type radicals caused by ?QOOH ring‐opening when the unpaired electron is localized adjacent to the ether group, and cis‐trans isomerization of ?R and ?QOOH radicals, via inversion, which enable reaction pathways otherwise restricted by stereochemistry. Several species were identified in the MPIMS experiments from ring opening of 2,3‐dimethyloxiranyl radicals. Neither of the two conjugate alkene isomers prototypical of ?R + O₂ reactions were detected. Products were also identified from decomposition of ketohydroperoxide‐type radicals. The present work provides the first analysis of 2,3‐dimethyloxirane oxidation chemistry and reveals that consumption pathways are complex and require the expansion of submechanisms in chemical kinetics mechanisms.     

The Profound Effect of the Ring Size in the Electrocyclic Opening of Cyclobutene‐Fused Bicyclic Systems

Fused cyclobutenes, prepared by the photocycloaddition of propargyl alcohols to cyclic anhydride chromophores, undergo facile thermochemical ring opening to fused γ‐lactones. The size of the fused ring profoundly influences the temperature that is required to facilitate the ring opening (from 50 °C to 180 °C) and the nature of the product that is formed. Our studies provide new insights into the mechanistic course of these reactions and have been extended to facilitate the preparation of lactams fused to medium‐sized rings.     

Mechanism and Selectivity of the Oxidative Ring Contraction of Cyclic α‐Formyl Ketones

The oxidative contraction of α‐formal ketone to form continuous all carbon chiral centers promoted by H₂O₂ is widely used in natural product total synthesis. Typically, using this transformation, chiral cyclic ketones are obtained as the major products and ring‐opening products as the minor products. Herein, DFT calculations have been used to investigate the detailed reaction mechanism and chemoselectivity. In addition, with the widely accepted mechanism of H₂O₂‐promoted transformation, our systematic investigation with various explicit‐solvent‐model calculations for the first time shows that H₂O and H₂O₂ are comparable at catalyzing the rate‐determining step of this reaction, which emphasis the importance of solvent effect in such transformations. It is found that both the less ring‐constrain and a later transition state in an exothermic reaction account for the origin why the reaction favors ring‐contraction pathway rather than ring‐opening one. By a comprehensive analysis for the substituted groups, it has been disclosed that the steric effects of the substituted groups on R² and R³ contribute to the selectivity with larger steric hindrance favoring the chiral cyclic products. Moreover, the electronic effects on R¹ but not R³ affect the selectivity with electron‐donating groups leading to the cyclic products. Based on our calculations, some predictions for higher selectivity have been made.     

Nucleophilic Reactivity of Ethers Against Terminal Epoxides in the Presence of BF3: A Mechanistic Study

In the presence of BF₃, a series of symmetrical and unsymmetrical ethers reacted with epichlorohydrin and 2‐[(benzyloxy)methyl]oxirane, two terminal epoxides, to afford 1‐alkoxy‐3‐chloropropan‐2‐ol and 1‐alkoxy‐3‐(benzyloxy)propan‐2‐ol. The cleavage of unsymmetrical ethers occurred via an S_N2 or S_N1 mechanism. Secondary epoxides did not give similar ring‐opening products.     

Polymerization of cyclic imino ethers: From its discovery to the present state of the art

Topics concerning the cationic ring‐opening polymerization of cyclic imino ethers and functional material production based on the resulting polymers are reviewed. Cyclic imino ethers are readily subjected to isomerization polymerization via cationic initiators. Mechanistic studies have provided a new concept, electrophilic polymerization. Double isomerization polymerization and no‐catalyst alternating copolymerization are interesting examples that show characteristics of the ring opening of cyclic imino ethers. The living polymerization of these monomers affords precisely controlled polymeric materials. Through the use of the unique properties of the product polymers, various functional polymeric materials, such as polymeric nonionic surfactants, compatibilizers, hydrogels, stabilizers for dispersion polymerization, biocatalyst modifiers, and supramolecular assemblies, have been developed. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 192–209, 2002     

Introduction of Alkyl- or Phenylseleno Group by the Ring Opening of Cyclic Ethers Using Dialkyl- or Alkylphenylselenium Dibromide and Sodium Borohydride

The reaction of dialkyl- or alkylphenylselenium dibromide with cyclic ethers in the presence of sodium borohydride gave ω-hydroxyalkyl alkyl or phenyl selenides as the ring opening products of the cyclic ethers.     

Ir‐Catalyzed Asymmetric Hydrogenation of α‐Alkylidene β‐Lactams and Cyclobutanones

Chiral β‐lactams and cyclobutanones are present in numerous natural and pharmaceutical products. The stereoselective construction of chiral four‐membered cyclic compounds is an ongoing challenge for the chemical community. Herein, we report a highly stereocontrolled construction of four‐membered ring (mini‐sized) β‐lactams and cyclobutanones via an Ir/ In‐BiphPHOX ‐catalyzed asymmetric hydrogenation, providing the corresponding optically active four‐membered ring carbonyl products bearing an α‐chiral carbon center with excellent yields (up to 99%) and enantioselectivities (up to 98%) under mild reaction conditions (1.0—2.5 bar H₂ for 1.0—10 h). The reaction presents wide substrate scope. Diverse transformations of the catalyzed products were also conducted to show the potential utility of this protocol.     

Gold‐Catalyzed Annulations of 2‐Alkynyl Benzaldehydes with Vinyl Ethers: Synthesis of Dihydronaphthalene,Isochromene, and Bicyclo[2.2.2]octane Derivatives

With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold‐catalyzed cyclizations of 2‐alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal‐tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2‐alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold‐catalyzed reactions of 2‐alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold‐catalyzed homo‐dimerization of 2‐phenylethynyl benzaldehyde 1 a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold‐containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place.