New facts concerning the reaction of K, K(15-crown-5)2 with phenyl glycidyl ether: unexpected formation of potassium cyclopropoxide

A new mechanism of the reaction of K⁻, K⁺(15-crown-5)₂ with phenyl glycidyl ether is presented. The linear ether bond is attacked only to a small extent, if at all. As the main reaction path the oxirane bond in the β-position is cleaved, followed by the γ-elimination of potassium phenoxide and the formation of potassium cyclopropoxide. Crown ether ring opening also occurs in reactions with organometallic intermediates.     

Enol silyl ethers via copper(II)-catalyzed C-O bond formation

Copper(II) acetate catalyzes the coupling of pinacol vinylboronates with silanols producing enol silyl ethers. This represents a novel enol silyl ether synthesis via formation of the C-O bond instead of the conventional Si-O bond. This also constitutes the first transition-metal-catalyzed oxidative cross-coupling with silanols.     

Direct Mechanism of the First Carbon–Carbon Bond Formation in the Methanol-to-Hydrocarbons Process

In the past two decades, the reaction mechanism of C−C bond formation from either methanol or dimethyl ether (DME) in the methanol-to-hydrocarbons (MTH) process has been a highly controversial issue. Described here is the first observation of a surface methyleneoxy analogue, originating from the surface-activated DME, by in situ solid-state NMR spectroscopy, a species crucial to the first C−C bond formation in the MTH process. New insights into the first C−C bond formation were provided, thus suggesting DME/methanol activation and direct C−C bond formation by an interesting synergetic mechanism, involving C−H bond breakage and C−C bond coupling during the initial methanol reaction within the chemical environment of the zeolite catalyst.     

Direct Mechanism of the First Carbon–Carbon Bond Formation in the Methanol‐to‐Hydrocarbons Process

In the past two decades, the reaction mechanism of C−C bond formation from either methanol or dimethyl ether (DME) in the methanol‐to‐hydrocarbons (MTH) process has been a highly controversial issue. Described here is the first observation of a surface methyleneoxy analogue, originating from the surface‐activated DME, by in situ solid‐state NMR spectroscopy, a species crucial to the first C−C bond formation in the MTH process. New insights into the first C−C bond formation were provided, thus suggesting DME/methanol activation and direct C−C bond formation by an interesting synergetic mechanism, involving C−H bond breakage and C−C bond coupling during the initial methanol reaction within the chemical environment of the zeolite catalyst.     

Shape- and Size-Tunable Synthesis of Covalent Organic Cages through Rh-Catalyzed Regioselective [2+2+2] Cycloaddition

Covalent organic cages have potential applications in molecular inclusion/recognition and porous organic crystals. Bridging arene units with sp³ atoms enables facile construction of rigid isolated internal vacancies, and various prismatic arene cages have been synthesized by kinetically controlled covalent bond formation. However, the synthesis of a tetrahedral one, which requires twice as much bond formation as prismatic ones, has been limited to a thermodynamically controlled dynamic S_NAr reaction, and this reversible covalent bond formation made the resulting cage product chemically unstable. Here we report the Rh-catalyzed high-yielding and highly 1,3,5-selective room temperature [2+2+2] cycloaddition of push-pull alkynes and its application to the synthesis of chemically stable aryl ether cages of various shapes and sizes, including prismatic and tetrahedral forms. These aryl ether cages are highly crystalline and intertwine with each other to form regular packing structures. Some aryl ether cages encapsulated isolated water molecules in their hydrophobic cavity by hydrogen bonding with the multiple ester moieties.     

Comparison of various coupling reagents in solid-phase aza-peptide synthesis

Aza-peptides are promising drug leads, however extensive study of their properties is hampered by low yielding aza-peptide bond formation during conventional Fmoc SPPS. The kinetics of aza-peptide bond formation in the model peptide H-Ala-AzAla-Phe-NH₂ was compared with various conventional amino acid activators. The reaction rates and yields were dependent on the activator structure. The reaction time of aza-peptide formation using oxyma-based agents was approximately 30 times longer than in typical peptide synthesis. Therefore, new activators are required to increase the reactivity of the activated amino acid to achieve effective acylation of the semicarbazide moiety during aza-peptide bond formation.     

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.     

Efficient assembly of α-aryl and α-vinyl nitriles via iron-catalyzed ether bond activation

A novel and practical method for the synthesis of diverse α-aryl and α-vinyl nitriles was developed via an iron-catalyzed sp³ C–O ether bond cleavage with C–C bond formation in the reaction of π-activated ethers with TMSCN.     

The β-cleavage reaction in ethers

β-Cleavage in n-butyl ethyl ether occurs neither by simple bond fission with oxiranium ion formation nor by a mechanism analogous to the γ-cleavage reaction in carbonyl compounds, but instead it involves skeletal rearrangement within the butyl chain.     

Direct Synthesis of Benzofuro[2,3‐b]pyrroles through a Radical Addition/[3,3]‐Sigmatropic Rearrangement/Cyclization/Lactamization Cascade

A straightforward synthetic method for the construction of benzofuro[2,3‐b]pyrrol‐2‐ones by a novel domino reaction through a radical addition/[3,3]‐sigmatropic rearrangement/cyclization/lactamization cascade has been developed. The domino reaction of O‐phenyl‐conjugated oxime ether with an alkyl radical allows the construction of two heterocycles with three stereogenic centers as a result of the formation of two C?C bonds, a C?O bond, and a C?N bond in a single operation, leading to pyrrolidine‐fused dihydrobenzofurans, which are not easily accessible by existing synthetic methods. Furthermore, asymmetric synthesis of benzofuro[2,3‐b]pyrrol‐2‐one derivatives through a diastereoselective radical addition reaction to a chiral oxime ether was also developed.     

Self-crosslinking of 2-hydroxypropyl-N-methylmorpholinium chloride cellulose fibres

Crosslinking of cellulose fibres was obtained by inducing a substitution reaction in a cationic cellulose ether (NMM-cellulose) prepared by action of N-oxiranylmethyl-N-methylmorpholinium chloride. During the reaction the N-methylmorpholine moiety of the cellulosic ether acts as a leaving group facilitating a covalent bond formation between the ether substituent and a hydroxyl or other nucleophilic group present in the cellulose chain. In order to provide additional evidence of the suggested crosslinking route and investigate its possibilities, different reaction conditions have been investigated and assessed in terms of the obtained fibre properties. The crosslinked fibres were characterized by means of elemental analysis and structure accessibility studies, including accessibility to water, anions and nitrogen gas. According to these investigations heating at 105 °C induces a significant crosslinking. Pre-treatment with acetone restricts it mainly to formation of intra-fibre crosslinks, whereas heating from water suppresses the reactivity but results nevertheless in highly crosslinked structure with both intra- and inter-fibre crosslinks involved.     

Ethers on Si(001): A Prime Example for the Common Ground between Surface Science and Molecular Organic Chemistry

By using computational chemistry it has been shown that the adsorption of ether molecules on Si(001) under ultrahigh vacuum conditions can be understood with classical concepts of organic chemistry. Detailed analysis of the two‐step reaction mechanism—1) formation of a dative bond between the ether oxygen atom and a Lewis acidic surface atom and 2) nucleophilic attack of a nearby Lewis basic surface atom—shows that it mirrors acid‐catalyzed ether cleavage in solution. The O−Si dative bond is the strongest of its kind, and the reactivity in step 2 defies the Bell–Evans–Polanyi principle. Electron rearrangement during C−O bond cleavage has been visualized with a newly developed method for analyzing bonding, which shows that the mechanism of nucleophilic substitutions on semiconductor surfaces is identical to molecular S_N2 reactions. Our findings illustrate how surface science and molecular chemistry can mutually benefit from each other and unexpected insight can be gained.     

Reductive cleavage of ether and thioether bonds on 1,3-benzodioxole and 1,3-benzoxathiole derivatives

The reaction of lithium and sodium diethylamide with 1,3-benzodioxoles and 1,3-benzoxathioles is here reported. 1,3-Benzodioxoles exhibit selective cleavage of the ether bond with formation of alkoxyphenols; 1,3-benzoxathioles when reacting with sodium diethylamide lead to 2-alkoxybenzenethiols while with lithium diethylamide give 2-alkoxybenzenethiols together with 2-(alkylthio)phenols.     

Organocatalytic, enantioselective intramolecular [6+2] cycloaddition reaction for the formation of tricyclopentanoids and insight on its mechanism from a computational study

Diphenylprolinol silyl ether was found to be an effective organocatalyst for promoting the asymmetric, catalytic, intramolecular [6 + 2] cycloaddition reactions of fulvenes substituted at the exocyclic 6-position with a δ-formylalkyl group to afford synthetically useful linear triquinane derivatives in good yields and excellent enantioselectivities. The cis-fused triquinane derivatives were obtained exclusively; the trans-fused isomers were not detected among the reaction products. The intramolecular [6 + 2] cycloaddition occurs between the fulvene functionality (6π) and the enamine double bond (2π) generated from the formyl group in the substrates and the diphenylprolinol silyl ether. The absolute configuration of the reaction products was determined by vibrational circular dichroism. The reaction mechanism was investigated using molecular orbital calculations, B3LYP and MP2 geometry optimizations, and subsequent single-point energy evaluations on model reaction sequences. These calculations revealed the following: (i) The intermolecular [6 + 2] cycloaddition of a fulvene and an enamine double bond proceeds in a stepwise mechanism via a zwitterionic intermediate. (ii) On the other hand, the intramolecular [6 + 2] cycloaddition leading to the cis-fused triquinane skeleton proceeds in a concerted mechanism via a highly asynchronous transition state. (iii) The fulvene functionality and the enamine double bond adopt the gauche-syn conformation during the C-C bond formation processes in the [6 + 2] cycloaddition. (iv) The energy profiles calculated for the intramolecular reaction explain the observed exclusive formation of the cis-fused triquinane derivatives in the [6 + 2] cycloaddition reactions. The reasons for the enantioselectivity seen in these [6 + 2] cycloaddition reactions are also discussed.     

Study of reaction of poly(butyl acrylate) radical with cobalt-porphyrin

Conclusions The reaction of poly(butyl acrylate) radical with a cobalt complex of dimethyl esterdimethyl ether of hematoporphyrin IX leads to the formation of a Co-C bond.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2830–2833, December, 1987.     

Vinyl aryl ethers from copper-catalyzed coupling of vinyl halides and phenols

A general procedure for vinyl aryl ether bond formation by direct coupling of vinyl halides and phenols under mild Ullmann-type reaction conditions has been developed. Using copper chloride as the catalyst and cesium carbonate as the base, vinyl bromides or iodides were reacted with phenols in refluxing toluene to produce vinyl aryl ethers in good to excellent yields.     

New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9,11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton.     

A computational study on addition of Grignard reagents to carbonyl compounds

The mechanism of stereoselective addition of Grignard reagents to carbonyl compounds has been investigated using B3LYP density functional theory calculations. The study of the reaction of methylmagnesium chloride and formaldehyde in dimethyl ether revealed a new reaction path involving carbonyl compound coordination to magnesium atoms in a dimeric Grignard reagent. The structure of the transition state for the addition step shows that an interaction between a vicinal-magnesium bonding alkyl group and C=O causes the C-C bond formation. The simplified mechanism shown by this model is in accord with the aggregation nature of Grignard reagents and their high reactivities toward carbonyl compounds. Concerted and four-centered formation of strong O-Mg and C-C bonds was suggested as a polar mechanism. When the alkyl group is bulky, C-C bond formation is blocked and the Mg-O bond formation takes precedence. A diradical is formed with the odd spins localized on the alkyl group and carbonyl moiety. Diradical formation and its recombination were suggested to be a single electron transfer (SET) process. The criteria for the concerted polar and stepwise SET processes were discussed in terms of precursor geometries and relative energies.     

Direct ether formation of semibenzopinacol moieties in a photopolymerization system featured constant intensity of absorbed light

In a special photopolymerization reaction system, the reactivity of semibenzopinacol moieties was examined. Structural analysis by 1D/2D NMR showed that the hydroxyl groups of the semibenzopinacol moieties after hydrogen abstraction reaction have reacted directly to form a new ether structure instead of the cleavage of a C-C bond in a photopolymerization system featured constant intensity of absorbed light when there is only vinyl acetate added. In order to clarify this new reaction, comparative experiments and several characterization methods were applied. Results revealed that poly(vinyl acetate) radicals initiated by UV irradiation or benzophenone/triethanolamine system, and UV irradiation under or above 300 nm, were two necessary factors for the formation of the new ether structure from hydroxyl groups of semibenzopinacol moieties.     

The kinetics of diethylene glycol formation in the preparation of polyethylene terephthalate

For revealing diethylene glycol (DEG) formation in poly(ethylene terephthalate) (PET) synthesis, this research focused on finding the stage most critical for DEG formation. It is found that the esterification stage was the most critical stage for DEG formation during production of PET through the direct esterification process. In addition, the kinetics of the formation of DEG (ether bond), which is mainly produced from hydroxyl end groups of ethylene glycol (EG) and bis-hydroxyethyl terephthalate (BHET) oligomer, was investigated. The results show that the reactivity of BHET-OH functional group is greater than that of EG-OH functional group in the reaction to produce ether bonds. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 3073–3080, 1998