Ring-expanded Products Research Articles

Insertion reactions involving a triamidoamine-supported zirconium complex

The reactivity of a triamidoamine-supported zirconium complex, [κ(5)-N,N,N,N,C-(Me(3)SiNCH(2)CH(2))(2)NCH(2)CH(2)NSiMe(2)CH(2)]Zr (1), toward polar, small-molecule substrates including isocyanides, organic azides, carbodiimides, nitriles, and ketones has been explored. The small-molecule substrates were found to react with the Zr-C bond of complex 1 via 1,1- or 1,2-insertion modes, affording ring-expanded products containing new zirconium-carbon, zirconium-nitrogen, or zirconium-oxygen bonds. Solid-state structures of a 1,1-insertion product [κ(6)-N,N,N,N,N,N-(Me(3)SiNCH(2)CH(2))(2)NCH(2)CH(2)NSiMe(2)CH(2)N(N=NCH(2)Ph)]Zr (3) and a 1,2-insertion product [κ(5)-N,N,N,N,O-(Me(3)SiNCH(2)CH(2))(2)NCH(2)CH(2)NSiMe(2)CH(2)CPh(2)O]Zr (5) are reported.

Reaction behavior of cyclopropylmethyl cations derived 1-phenylselenocyclopropylmethanols with acids

The 1-phenylselenocyclopropylmethyl cations are generated by the reaction of the corresponding cyclopropylmethanols 1 with TsOH. The reaction in methanol proceeds to afford the homoallylic ethers 2, ring-enlargement products 3, 4, and ring opening products 5 depending upon the kind of substituent on the cyclopropane ring or the α-carbon. On the other hand, in the case of the absence of methanol as nucleophile, 4 H-selenochromene derivative 7 is obtained exclusively. The oxidative elimination of the phenylselenyl group in the resulting phenylselenohomoallylic compounds 2 furnishes functionalized allene derivatives and alkyne derivatives.

Silver Ion-Assisted Ring Expansions in Different Solvent Systems

Several ring expansion products carrying vinylic bromo functionality were synthesized by opening of the geminal dibromobicyclo[n.1.0]alkanes ring. Dibromocarbene was formed from bromoform and potassium tert-butoxide in hexane. Its reaction with various cyclic alkenes was the resultant dibromobicyclo[n.1.0]alkanes. Then, opening was performed using AgNO_3 in various solvent systems, such as acetic acid/DMSO, acetic acid/DMF, CH_3OH/acetone, and H_2O/DMF.

4-Halo-1,3-oxazoles: Unambiguous structural assignment of 2-halo-2-benzoyl-2 H-azirine-3-carboxylates thermal ring expansion products

IR spectroscopy in cryogenic argon matrix of methyl 4-chloro-5-phenyl-1,3-oxazole-2-carboxylate and methyl 4-chloro-5-phenylisoxazole-3-carboxylate was applied for the structural assignment of these isomeric heterocycles. It was demonstrated that methyl 2-benzoyl-2-halo-2 H-azirine-3-carboxylates undergo thermal ring expansion to give 4-halo-5-phenyl-1,3-oxazole-2-carboxylates and not the isomeric isoxazoles.

Acid-catalyzed Reaction Behavior of 1-Phenylselenocyclopropylmethanols

Abstract The reaction of 1-phenylselenocyclopropylmethanols with TsOH in methanol proceeded smoothly to afford the homoallylic ethers, ring-enlargement products, and ring-opening products depending upon the kind of substituent on the cyclopropane ring or α-carbon. On the other hand, in the case of the absence of methanol as nucleophile, 4H-selenochromene derivatives were obtained exclusively.

Hydroconversion of methylcyclopentane over Pt/HZSM-5 catalyst: I. Effects of reaction parameters on ring enlargement reaction

The effects of reaction parameters such as temperature, pressure, and hydrogen to hydrocarbon ratio (H 2/HC) on the hydroconversion of methylcyclopentane (MCP) over Pt/HZSM-5 have been investigated in a fixed-bed down-flow reactor. The catalytic evaluation results were compared with the thermodynamic calculation data in order to investigate the behavior of MCP Ring enlargement (RE) reaction. Methylcyclopentane hydro conversion is described as a linear combination of three reactions: ring enlargement (RE), ring opening (RO) and cracking (CR), and RE reaction produces cyclohexane (CH) and benzene (Bz). It was shown that the conversion of MCP increased with the increase in temperature or with the decrease in H 2/HC ratio, whereas decreased with the increase of pressure. The influence of the reaction parameters on the RE selectivity presented a complicated picture. With the increase in temperature, the RE selectivity first increased and then decreased, showing a maximum at a certain temperature. The effect of the H 2/HC mol ratio was found to be relevant with temperature. At lower reaction temperatures, the RE selectivity decreased with decrease in the H 2/HC ratio. However, at higher reaction temperatures, the H 2/HC mol ratio had little influence on RE selectivity. The distribution of RE products between CH and Bz provides information on the reaction pathway. The experimental Bz/CH ratio was in excess of the equilibrium value, which strongly suggested that Bz, as the same as CH, could be a primary product from MCP. Thus, a modified reaction pathway of RE reaction could be proposed as follows: both CH and Bz were produced from the same intermediate, which was an adsorbed species on the dual function catalyst formed from MCP. In other words, the isomerization and dehydroisomerization are parallel reactions, producing CH and Bz, respectively. Meanwhile, Bz can come from CH through dehydrogenation.

Evidence from Mechanistic Probes for Distinct Hydroperoxide Rearrangement Mechanisms in the Intradiol and Extradiol Catechol Dioxygenases

Three mechanistic probes were used to investigate whether the Criegee rearrangement step of catechol 1,2-dioxygenase (CatA) from Acinetobacter sp. proceeds via a direct 1,2-acyl migration, via homolytic O-O cleavage, or via a benzene oxide-oxepin rearrangement. Incubation of CatA with 3-chloroperoxybenzoic acid led to the formation of a 9:1 mixture of 2-chlorophenol and 3-chlorophenol, via a mechanism involving O-O homolytic cleavage. Incubation of CatA with 2-hydroperoxy-2-methylcyclohexanone led to formation of 5,6-diketoheptan-1-ol, also consistent with an O-O homolytic cleavage mechanism, and not consistent with a direct 1,2-acyl migration. No reaction product was isolated from incubation of CatA with 6-hydroxymethyl-6-methylcyclohexa-2,4-dienone, an analogue that is able to undergo the benzene oxide-oxepin rearrangement, but not able to undergo O-O homolytic cleavage. In contrast, incubation of extradiol dioxygenase MhpB from Escherichia coli with 6-hydroxymethyl-6-methylcyclohexa-2,4-dienone led to the formation of a 2-tropolone ring expansion product, consistent with a direct 1,2-alkenyl migration for extradiol cleavage. Taken together, the results imply different mechanisms for the Criegee rearrangement steps of intradiol and extradiol catechol dioxygenases: a direct 1,2-alkenyl migration for extradiol cleavage and an O-O homolytic cleavage mechanism for intradiol cleavage.

Evidence for a Morin type intramolecular cyclization of an alkene with a phenylsulfenic acid group in neutral aqueous solution.

Sulfenic acids (RSOH) are among the most common sulfur-centered reactive intermediates generated in biological systems. Given the biological occurrence of sulfenic acids, it is important to explore the reactivity of these intermediates under physiological conditions. The Morin rearrangement is a synthetic process developed for the conversion of penicillin derivatives into cephalosporins that proceeds via nucleophilic attack of an alkene on a sulfenic acid intermediate. In its classic form, the Morin reaction involves initial elimination of a sulfenic acid from a cyclic sulfoxide, followed by intramolecular cyclization of the resulting alkene and sulfenic acid groups to generate an episulfonium ion intermediate that undergoes further reaction to yield ring-expanded products. On the basis of the existing literature, it is difficult to assess whether the reaction between an alkene and a sulfenic group can occur under mild conditions because the conditions required to generate the sulfenic acid from the sulfoxide precursor in the Morin reaction typically involve high temperatures and strong acid. In the work described here, beta-sulfinylketone precursors were used to generate a "Morin type" sulfenic acid intermediate under mild conditions. This approach made it possible to demonstrate that the intramolecular cyclization of an alkene with a phenylsulfenic acid to generate an episulfonium ion intermediate can occur in neutral aqueous solution at room temperature.

Stereoselective Preparation and Cope Rearrangement of 2-CF3-cis-2,3-bis(alkenyl)oxiranes: A Facile Route to 2-CF3-Substituted Oxacycles

We describe here a facile route to 2-trifluoromethyl-substituted 4,5-dihydrooxepins, which involves stereoselective preparation and Cope rearrangement of 2-trifluoromethyl-cis-2,3-bis(alkenyl)oxiranes. Treatment of 1,1-dichloro-2-hydroxy-2-trifluoromethylalk-3-enes with alkenyllithium and then lithium 2,2,6,6-tetramethylpiperidide generated cis-2,3-bis(alkenyl)-2-lithio-3-trifluoromethyloxiranes, which reacted with a variety of electrophiles to give the corresponding tri- and tetrasubstituted oxiranes stereoselectively. Cope rearrangement of the cis-oxiranes proceeded upon heating, giving rise to 2-trifluoromethyl-substituted 4,5-dihydrooxepins in high to excellent yields. The Cope rearrangement is found remarkably accelerated by the presence of such metal substituents as boryl, silyl, and stannyl groups at 7-position, that can act as versatile functionalities for further elaboration of the ring-enlarged products. Subsequent reduction and oxidation of the rearranged products gave 2-trifluoromethylated oxepanes and oxepins in good yields.

Expansion of the pentafluorobenzene ring of perfluoro-1,2-diethyl-1-phenylbenzocyclobutene under the action of SbF 5

Perfluoro-1,2-diethyl-1-phenylbenzocyclobutene under the action of SbF 5 gives, after treatment of the reaction mixture with water, perfluoro-4-[1-(6-propyl-phenyl)-propylidene]cyclohexa-2,5-dienone along with the products of unusual pentafluorobenzene ring expansion – perfluorinated 4 b,10-diethylbenzo[ a]azulen-7(4 bH)-one and 10-ethylbenzo[ a]azulen-6(10 H)-one.

Nickel(I) Salen-Catalyzed Reduction of 1-Haloalkyl-2-oxocycloalkanecarboxylates: Three- and Four-Carbon Ring Expansions

Cyclic voltammetry and controlled-potential electrolysis have been employed to study the catalytic reduction of methyl 1-(4-halobutyl)-2-oxocyclopentanecarboxylate and ethyl 1-(3-halopropyl)-2-oxocyclohexanecarboxylate by nickel(I) salen electrogenerated at carbon cathodes in dimethylformamide containing tetramethylammonium tetrafluoroborate. Electrocatalytic reduction of the aforementioned compounds, in either their bromo or iodo forms, affords the corresponding ring-expanded products (methyl cyclononanone-5-carboxylate and ethyl cyclononanone-5-carboxylate) in up to 26% yield, along with the dehalogenated species (methyl 1-butyl-2-oxocyclopentanecarboxylate and ethyl 1-propyl-2-oxocyclohexanecarboxylate) and their unsaturated counterparts [methyl 1-(but-3-enyl)-2-oxocyclopentanecarboxylate and ethyl 1-allyl-2-oxocyclohexanecarboxylate]. However, the principal products are dimers—dimethyl -(octane-1,8-diyl)bis(2-oxocyclopentanecarboxylate) derived from methyl 1-(4-halobutyl)-2-oxocyclopentanecarboxylate, and diethyl -(hexane-1,6-diyl)bis(2-oxocyclohexanecarboxylate) arising from ethyl 1-(3-halopropyl)-2-oxocyclohexanecarboxylate—obtained in yields ranging from 52% to 83%. A mechanistic scheme, involving alkyl radicals formed via nickel(I) salen-catalyzed cleavage of the carbon-halogen bond of each substrate, is proposed to account for the formation of the various products.

PhI(OAc) 2-mediated additions of 2,4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB)

We report herein stereoselective additions of a nitrene derived from PhI(OAc) 2 and 2,4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB) to give the corresponding ring enlargement products, (cyclobutylidene)amide or (cyclopentylidene)amide derivatives, in moderate to excellent yields. The reaction mechanism has been discussed on the basis of control experiments and previous investigation.

Radical Intermediates in Monooxygenase Reactions of Rieske Dioxygenases

Rieske dioxygenases catalyze the cis-dihydroxylation of a wide range of aromatic compounds to initiate their biodegradation. The archetypal Rieske dioxygenase naphthalene 1,2-dioxygenase (NDOS) catalyzes dioxygenation of naphthalene to form (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. NDOS is composed of three proteins: a reductase, a ferredoxin, and an α3β3 oxygenase (NDO). In each α subunit, NDO contains a Rieske Fe2S2 cluster and a mononuclear iron site where substrate dihydroxylation occurs. NDOS also catalyzes monooxygenase reactions for many substrates. The mechanism of the reaction is unknown for either the mono- or dioxygenase reactions but has been postulated to involve direct reaction of either a structurally characterized Fe(III)−hydroperoxy intermediate or the electronically equivalent Fe(V)−oxo−hydroxo intermediate formed by O−O bond cleavage before reaction with substrate. The reaction for the former intermediate is expected to proceed through cationic intermediates, while the latter is anticipated to initially form a radical intermediate. Here the monooxygenation reactions of the diagnostic probe molecules, norcarane and bicyclohexane, are investigated. In each case, a significant amount of the rearrangement product derived from a radical intermediate (lifetime of 11−18 ns) is observed, while little or no ring expansion product from a cationic intermediate is formed. Thus, monooxygenation of these molecules appears to proceed via the Fe(V)−oxo−hydroxo intermediate. The formation of this high-valent intermediate shows that it must also be considered as a possible participant in the dioxygenation reaction, in contrast to computational studies but in accord with previous biomimetic studies.

Synthesis of (.+‐.)‐Strychnofoline via a Highly Convergent Selective Annulation Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Double α‐Ketol Rearrangement of (‐)‐1‐{(1S,2R,4R)‐1‐Ethenyl‐2‐hydroxy‐7,7‐dimethylbicyclo [2.2.1]hept‐2‐yl}ethan‐1‐one.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

TiCl4 Induced Anti-Markovnikov Rearrangement

Stereoisomeric bicyclic tert-alcohols afforded identical ring-expansion products via cationic anti-Markovnikov rearrangement from perpendicular tert-cations into identical six-membered ring secondary cations by the treatment with TiCl4. These results provide evidence that the reaction takes place by the cationic stepwise mechanism. [reaction: see text]

Synthesis of (±)‐Strychnofoline via a Highly Convergent Selective Annulation Reaction

Studies aimed at preparing (+/-)-strychnofoline by total synthesis are detailed. The route described makes use of a recently developed MgI(2)-mediated ring-expansion reaction of spiro[cyclopropan-1,3'-oxindole] with a cyclic disubstituted aldimine. The ring-expansion product was formed as a single diastereoisomer in 55 % yield, possessing the same stereochemical pattern found in strychnofoline. In addition, our synthetic effort has led to the development of new reaction methodology to access 3,4-disubstituted cyclic aldimines.

Base-mediated hydrolytic cleavage with chain migration of 1-chloromethyl-tetrahydropyrano[3,4- b]indoles: an unusual pathway to 2-succinoyl tryptophols

An unusual hydrolytic cleavage with 1,2-alkyl chain migration of 1-chloromethyl-tetrahydropyrano[3,4- b]indoles by heating with a limited amount of water and base in DMF is reported. A mechanism for the formation of 1,2-alkyl chain migration products, 2-succinoyl tryptophols, and the ring-expansion products, dihydro-oxepine fused indoles, is reported. No comparable 1,2-chain migration from a structurally related 1-chloromethyl-isochroman is observed.

A Novel Bromine-Induced Ring Expansion of the Spiroimine Moiety of the Shellfish Toxin Gymnodimine

Treatment of the shellfish toxin gymnodimine with one equivalent of molecular bromine at -78 °C resulted in stereoselective formation of a novel ring-expansion product. Participation of the spiromine unit in this novel bromine-induced ring expansion reaction provides insight into how the reactivity of spiroimine moiety may contribute to the toxicity of this marine biotoxin when activated by the presence of an appropriate environmental electrophile.

Double α-ketol rearrangement of (−)-1-{(1S,2R,4R)-1-ethenyl-2-hydroxy-7,7-dimethylbicyclo[2.2.1]hept-2-yl}ethan-1-one

The title compound undergoes α-ketol rearrangement by the action of Lewis acids and bases to give the expected and double-rearrangement ring expansion products. Some specific features of the process are discussed.