Oxonium Ion Intermediates Research Articles

Study on the fluorination of 1, 2-O-isopropylidene D-pentofuranose with DAST and its scalable application

The research focuses on the inversion of configuration at C3 of 1,2-O-isopropylidene-d-arabinofuranoside and d-ribofuranoside promoted by DAST. Both the initial configuration and the presence of C5 acyl group in d-furanosides are the key factors for this inversion due to the formation of cyclic oxonium ion intermediates. This inversion of configuration has been successfully applied to scalable synthesis of d-lyxose and 2′,5′-di-O-benzoyl-3′-fluoro-3′-deoxy-β-d-ribofuranosyl-7-halogen-7-deazapurine.

Involvement of an Oxonium Ion Intermediate in Controlling the Diastereoselectivity of Nucleophilic Substitution Reactions of Septanoses.

The alkoxy substituents at C4 and C2 of septanoses control the stereochemical outcomes of O-glycosylation reactions of these seven-membered-ring intermediates. Isolation of a bicyclic acetal byproduct in some substitution reactions suggests that the C4 benzyloxy substituent engaged in long-range participation, stabilizing intermediates by the formation of an oxonium ion intermediate. Inductive destabilization of the carbocationic intermediate provided by the C2 substituent is crucial to the participation of the remote alkoxy group.

Synthesis of 4‐Acylchromene via Highly Chemoselective Iodine‐Catalyzed Cyclization of Alkynylarylether Dimethylacetals

4-Acylchromene is an important core structure found in bioactive natural products and bioactive synthetic compounds. Moreover, this core structure is frequently used as a key precursor for the synthesis of more complex molecules. In this work, we discovered that a combination of acetone and catalytic I2 could lead to selective activation of acetal in alkynylarylether dimethylacetal substrates while alkyne moiety remained intact. This activation of acetal led to the generation of oxonium ion intermediate which triggered intramolecular cyclization and elimination of methanol to provide the desired 4-acylchromene as the sole product in up to 95% yield. Moreover, this method could be applied in a broad range of substrates under a mild and metal-free catalytic conditions for the synthesis of 4-acylchromene derivatives.

Palladium‐Catalyzed Cross‐Coupling of Furfuryl Alcohols with Arylboronic Acids via Aromatization‐Driven Carbon−Carbon Bond Cleavage to Synthesize 5‐Arylfurfuryl Alcohols and 2,5‐Diaryl Furans

AbstractHerein we report a protocol for novel palladium‐catalyzed cross‐coupling reactions of sustainably produced primary furfuryl alcohols with arylboronic acids to deliver 5‐arylfurfuryl alcohols and 2,5‐diaryl furans. Hammett plot analysis suggested that the reaction mechanism involved aromatization‐driven cleavage of the carbon−carbon bond of a furan oxonium ion intermediate. This protocol provides a simple, practical way to transform 5‐hydroxymethylfurfural into useful compounds.magnified image

Switching between Anion-Binding Catalysis and Aminocatalysis with a Rotaxane Dual-Function Catalyst.

The "off" state for aminocatalysis by a switchable [2]rotaxane is shown to correspond to an "on" state for anion-binding catalysis. Conversely, the aminocatalysis "on" state of the dual-function rotaxane is inactive in anion-binding catalysis. Switching between the different states is achieved through the stimuli-induced change of position of the macrocycle on the rotaxane thread. The anion-binding catalysis results from a pair of triazolium groups that act together to CH-hydrogen-bond to halide anions when the macrocycle is located on an alternative (ammonium) binding site, stabilizing the in situ generation of benzhydryl cation and oxonium ion intermediates from activated alkyl halides. The aminocatalysis and anion-binding catalysis sites of the dual-function rotaxane catalyst can be sequentially concealed or revealed, enabling catalysis of both steps of a tandem reaction process.

ChemInform Abstract: Synthesis of Polyketide Stereoarrays Enabled by a Traceless Oxonia‐Cope Rearrangement.

Polyketide antibiotics bearing skipped polyols represent a synthetic challenge. A SiCl4-promoted oxonia-Cope rearrangement of syn,syn-2-vinyl-1,3-diols was developed to forge an array of 1,5-pentenediols, thus providing versatile motifs for the preparation of 1,2,3,5-stereoarrays in a highly stereoselective manner. Further exploration with Sn(OTf)2 realized the rearrangement of a cross-aldehyde which tactically warrants the utility of the current approach to access complex polyketides. The origin of high stereoselectivity is attributed to a chairlike anti-conformation of the oxonium ion intermediate.

Synthesis of polyketide stereoarrays enabled by a traceless oxonia-Cope rearrangement.

Polyketide antibiotics bearing skipped polyols represent a synthetic challenge. A SiCl4-promoted oxonia-Cope rearrangement of syn,syn-2-vinyl-1,3-diols was developed to forge an array of 1,5-pentenediols, thus providing versatile motifs for the preparation of 1,2,3,5-stereoarrays in a highly stereoselective manner. Further exploration with Sn(OTf)2 realized the rearrangement of a cross-aldehyde which tactically warrants the utility of the current approach to access complex polyketides. The origin of high stereoselectivity is attributed to a chairlike anti-conformation of the oxonium ion intermediate.

Synthesis of Polyketide Stereoarrays Enabled by a Traceless Oxonia‐Cope Rearrangement

AbstractPolyketide antibiotics bearing skipped polyols represent a synthetic challenge. A SiCl4‐promoted oxonia‐Cope rearrangement of syn,syn‐2‐vinyl‐1,3‐diols was developed to forge an array of 1,5‐pentenediols, thus providing versatile motifs for the preparation of 1,2,3,5‐stereoarrays in a highly stereoselective manner. Further exploration with Sn(OTf)2 realized the rearrangement of a cross‐aldehyde which tactically warrants the utility of the current approach to access complex polyketides. The origin of high stereoselectivity is attributed to a chairlike anti‐conformation of the oxonium ion intermediate.

A Hetero Diels–Alder Approach to the Synthesis of Chromans (3,4-Dihydrobenzopyrans) Using Oxonium Ion Chemistry: The Oxa-Povarov Reaction

An oxa analogue of the well-known Povarov reaction has been developed for the synthesis of 3,4-dihydrobenzopyrans (chromans). The reaction involves the formal inverse electron demand [4 + 2] cycloaddition reaction of in situ-generated cationic aryl 2-oxadiene oxocarbenium ions with alkenes. The oxonium ion intermediates are generated through Lewis acid (SnCl(4))-promoted reactions of phenol-derived Rychnovsky-type mixed acetals. The yield and diastereoselectivity of the chroman products are found to depend upon the substitution pattern of the precursor alkene (i.e., monosubstituted, trans- or cis-disubstituted and cyclic alkenes). Generally, the reactions afford the endo-diastereomers as the major products, except for the reactions of trans-β-methylstyrene, which afford exo-chromans. A comparison of the product distributions from the reactions of trans- and cis-β-methylstyrene reveal that the reaction proceeds, at least in part, by a nonconcerted ionic pathway. Just as for the aza-Povarov reaction, there are two potential mechanisms for the reaction. The first mechanism involves a direct asynchronous [4 + 2] cycloaddition pathway, while the second occurs through the stepwise Prins addition of the alkene to the aryl 2-oxadiene oxonium ion, followed by an intramolecular aromatic substitution reaction of the resultant cation (i.e., a domino Prins/intramolecular Friedel-Crafts reaction).

ChemInform Abstract: Intramolecular Haloetherification of Ene‐ and Diene‐Acetals: Asymmetric Synthesis Involving Chiral Oxonium Ion Intermediates

AbstractReview: about 50 refs.

Intramolecular Haloetherification of Ene- and Diene-Acetals: Asymmetric Synthesis Involving Chiral Oxonium Ion Intermediates

Asymmetric processes, taking place via the intermediacy of chiral oxonium ions arising from intramolecular haloetherification reactions of chiral ene- and diene-acetals of optically pure C 2-symmetric hydrobenzoine, have been developed. A novel, double intramolecular haloetherification process was observed. The asymmetric reactions developed in this effort were applied to the synthesis of several natural products, including solenopsin A, (cis-6-methyltetrahydropyran-2-yl)acetic acid, the pheromone of the wasp Paravespula vulgaris, rubrenolide, rubrynolide, scyphostatin, cryptocaryone, Sch 642305, and clavolonine. The strategies used in these syntheses involved a new concept called ‘chiral auxiliary multiple-use methodology’. In addition, intramolecular haloetherification reactions of ene-acetals, derived from chiral optically pure norbornene aldehydes and meso-diols, were applied to asymmetric desymmetrization of meso-diols. Finally, a new method for the resolution of racemic norbornene aldehydes, utilizing chiral ene-acetal oxonium ion intermediates produced from optically pure hydrobenzoin, was developed.

Stereoselective C-glycosidations with achiral and enantioenriched allenylsilanes.

Allenylsilanes are used as carbon nucleophiles in highly stereoselective Lewis acid-promoted C-glycosidations, resulting in the introduction of an internal alkyne with an adjacent stereocenter. Both achiral and chiral allenylsilanes form the desired products with high diastereoselectivity, where the nucleophile adds exclusively to the α-face of the intermediate oxonium ion. Reactions with glucal and galactal afford dihydropyran products, while reactions with a ribose derivative yield dihydrofuran products.

Immobilization of β-galactosidase onto Sepharose and stabilization in room temperature ionic liquids

The hydrolysis of o-nitrophenyl-β- d-galactopyranoside (ONPG) by β-galactosidase immobilized on Sepharose CL-4B ® was investigated in five different ionic liquids (ILs), 1-butyl-3-methylimidazolium X −; [ X = CF 3SO 3 −, BF 4 −, PF 6 −, CH 3SO 4 −and N(CN) 2 −]. Michaelis–Menten kinetic studies were conducted in phosphate buffer and in the five ionic liquids. For the immobilized enzyme in the ILs, the K m values were lower (0.36–1.2 mmol ONPG) while the V max values were higher (0.04–0.008 min − 1 ) compared to those in aqueous phosphate buffer suggesting a marked increase in the efficiency of the immobilized enzyme in the ionic liquid. For the free enzyme in the ionic liquids, the K m values, in general, were larger (0.45–4.96 mmol ONPG) than those of the immobilized enzyme in the ionic liquid. A postulated mechanism for the hydrolysis is suggested, involving interception of the intermediate oxonium ion species by the counter ion of the ionic liquid, thereby enabling the hydrolysis to occur at a faster rate.

B(C 6F 5) 3 catalyzed dehydrocarbon polycondensation of PhSiH 3 with (MeO) 4Si as model polyfunctional comonomers in new route to hydrophobic silicone TQ resins

Highly branched methoxy substituted phenylsilsesquioxane-silicate copolymers were obtained by dehydrocarbon polycondensation of phenylsilane (PhSiH 3) with tetramethoxysilane (TMOS) in toluene solution catalyzed by tris(pentafluorophenyl)borane [B(C 6F 5) 3]. This model reaction represents a new non-hydrolytic route to TQ silicone resins, which do not contain reactive and hydrophilic silanol groups and therefore, should be more stable and have better miscibility with some organic polymers. The soluble siloxane copolymers, which do not contain volatile oligomers, were obtained using the PhSiH 3:TMOS molar ratios below 0.9. The dehydrocarbon condensation is accompanied by metathetic exchange of hydrosilyl and methoxysilyl functions, which is responsible for the formation of links between units originating from the same comonomer. Competition between the dehydrocarbon condensation and metathesis is consistent with a mechanism involving the transient formation of a tertiary oxonium ion intermediate. 29Si NMR analysis of the copolymer product proves that extensive cyclization occurs during the polycondensation, most likely leading to a significant proportion of ladder and cage like structures.

Scope and Mechanism of the Iridium-Catalyzed Cleavage of Alkyl Ethers with Triethylsilane

The cationic iridium pincer complex [(POCOP)Ir(H)(acetone)](+)[B(C(6)F(5))(4)](-) {1, POCOP = 2,6-[OP(tBu)(2)](2)C(6)H(3)} was found to be a highly active catalyst for the room-temperature cleavage and reduction of a wide variety of unactivated alkyl ethers including primary, secondary, and tertiary alkyl ethers as well as aryl alkyl ethers by triethylsilane. Mechanistic studies have revealed the full details of the catalytic cycle with the catalyst resting state(s) depending on the basicity of the alkyl ether. During the catalytic reduction of diethyl ether, cationic iridium silane complex, [(POCOP)Ir(H)(eta(1)-Et(3)SiH)](+)[B(C(6)F(5))(4)](-) (3), and Et(2)O are in rapid equilibrium with neutral dihydride, (POCOP)Ir(H)(2) (5) and diethyl(triethylsilyl)oxonium ion, [Et(3)SiOEt(2)](+)[B(C(6)F(5))(4)](-) (7), with 5 + 7 strongly favored. Species 7 has been isolated from the reaction mixture and fully characterized. The turnover-limiting step in this cycle is the reduction of 7 by the neutral dihydride 5. The relative rates of reduction of 7 by dihydride 5 and Et(3)SiH were determined to be approximately 30,000:1. In the cleavage of the less basic ethers anisole and EtOSiEt(3), the cationic iridium silane complex, 3, was found to be the catalyst resting state. The hydride reduction of the intermediate oxonium ion EtO(SiEt(3))(2)(+), 9, occurs via attack by Et(3)SiH. In the case of anisole, the intermediate PhMeOSiEt(3)(+), 10, is reduced by 5 and/or Et(3)SiH.

Effect of Temperature on the Cationic Photopolymerization of Epoxides

The effects of temperature on the photoinitiated cationic ring‐opening polymerizations of a number of different epoxide monomers were studied with the aid of a modified optical pyrometer instrument. Depending on the structures of the epoxide monomer, various behaviors were observed. The results were interpreted as due to steric and electronic features inherent in the structures of the monomers that affect the stabilization of the secondary oxonium ions, which are formed as intermediates in these polymerizations. At one extreme, cycloaliphatic epoxides such as cyclohexene oxide give highly reactive oxonium intermediates that exhibit high rates of polymerization even at subambient temperatures. At the other extreme, alkyl glycidyl ethers produce oxonium ion intermediates, which are so stable that they do not spontaneously react to form polymer at room temperature. By manipulation of the structure of the epoxide monomer, novel monomers with tailored reactivities can be prepared.

A Ring‐Fusion/Ring‐Fission Mechanism for the Metathesis Reaction of Macrocyclic Formaldehyde Acetals

Important insight has been obtained into the mechanism of the reversible acid-catalysed transacetalation of cyclophane formaldehyde acetals (formals) C(i) in CDCl(3), at 25 degrees C. The order of appearance of the lowest oligomers in the early stages of the equilibration reaction is fully consistent with ring-fusion/ring-fission processes in which oxonium ion intermediates undergo S(N)2 reactions, according to an acid-catalysed bimolecular (A2) mechanism. The alternative acid-catalysed monomolecular (A1) reaction path, based on "back-biting" processes of carbenium ions generated by S(N)1-type cleavage of oxonium ion intermediates, predicts sequences that are in marked contrast with experimental findings.

Synthesis and Lewis acid induced isomerization of mono-, di-, and tri-spiro α-keto tetrahydro-furans and -pyrans

The stereoselectivity of the acid-catalyzed ring expansion of dihydrofuranyl and dihydropyranyl 1,2-adducts to spirocyclic ketones 8 and 9 has been examined. These substrates have become readily available by the utilization of 1,3-dichloroacetone as a synthetic equivalent of cyclopropanone. The kinetically controlled isomerizations result in ring expansion to dispirocyclopentanones. Third-stage conversion to trispirocyclohexanones was shown to be possible in select examples. On a different front, the syn and anti pairs proved capable of interconversion by heating in the presence of boron trifluoride etherate. A push–pull fragmentation of the ketone ring is proposed to account for these epimerizations. Calculations have been performed to simulate transition state energies in the oxonium ion intermediates and to gain some idea of the preferred ground-state geometries of the final products.Key words: oxonium ion rearrangements, ring expansions, acid-catalyzed epimerizations, cyclopropanone equivalent, spirocyclic ethers.

Design and synthesis of multifunctional glycidyl ethers that undergo frontal polymerization

AbstractAn investigation of the photoactivated cationic ring‐opening frontal polymerizations of a series of alkyl glycidyl ethers has been carried out with the aid of a novel technique, optical pyrometry. With this technique, the effects of the monomer structure on the frontal behavior of these monomers have been examined. Upon irradiation with UV light, the photopolymerizations of many alkyl glycidyl ethers display a prolonged induction period at room temperature as the result of the formation of long‐lived, relatively stable secondary oxonium ions. The input of only a small amount of thermal activation energy is required to induce the further reaction of these species with a consequent autoaccelerated exothermic ring‐opening polymerization. Photoactivated frontal polymerizations have been observed for both mono‐ and polyfunctional alkyl glycidyl ether monomers. The ability of monomers to exhibit frontal behavior has been found to be related to their ability to stabilize the secondary oxonium ion intermediates through multiple hydrogen‐bonding effects to the ether groups present in the molecule. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6435–6448, 2006

Cationic photopolymerization of alkyl glycidyl ethers

AbstractAn investigation of the photoactivated cationic ring‐opening frontal polymerizations of a series of alkyl glycidyl ethers was carried out with the aid of a novel technique, optical pyrometry. With this technique, the effects of various experimental parameters, such as the photoinitiator type and concentration, as well as the effects of the monomer structure on the frontal behavior of these monomers were examined. Upon irradiation with UV light, the photopolymerizations of many alkyl glycidyl ethers displayed a prominent induction period at room temperature as the result of the formation of long‐lived, relatively stable secondary oxonium ions. The input of only a small amount of thermal activation energy was required to induce the further reaction of these species with the consequent autoaccelerated exothermic ring‐opening polymerization. Photoactivated frontal polymerizations were observed for both mono‐ and polyfunctional alkyl glycidyl ether monomers. The ability of monomers to exhibit frontal behavior was found to be related to their ability to stabilize the secondary oxonium ion intermediates through hydrogen‐bonding effects. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3036–3052, 2006