Oxidative rearrangement of tertiary allylic alcohols employing oxoammonium salts

Practical and highly efficient methods for oxidative rearrangement of tertiary allylic alcohols to beta-substituted alpha,beta-unsaturated carbonyl compounds employing oxoammonium salts are described. The methods developed are applicable to acyclic substrates as well as medium membered ring substrates and macrocyclic substrates. The counteranion of the oxoammonium salt plays crucial roles on this oxidative rearrangement.     

Regioselectivity switch: gold(i)-catalyzed oxidative rearrangement of propargyl alcohols to 1,3-diketones

The gold(I)-catalyzed oxidative rearrangement of propargyl alcohols provides an efficient and selective route to 1,3-diketones under mild conditions. Pyridine-N-oxides were used as external oxidants with, different from related substrates, no alkylidenecycloalkanones or oxetan-3-ones formed as side-products.     

Tropylium ion mediated α-cyanation of amines

Tropylium ion mediated α-cyanation of amines is described. Even in the presence of KCN, tropylium ion is capable of oxidizing various amine substrates, and the resulting iminium ions undergo salt metathesis with cyanide ion to produce aminonitriles. The byproducts of this transformation are simply cycloheptatriene, a volatile hydrocarbon, and water-soluble potassium tetrafluoroborate. Thirteen total substrates are shown for the α-cyanation procedure, including a gram scale synthesis of 17β-cyanosparteine. In addition, a tropylium ion mediated oxidative aza-Cope rearrangement is demonstrated.     

Synthesis of some new lignans and the mechanism of intramolecular nonphenolic oxidative coupling of aromatic compounds

Treatment of cis-1,4-diaryl-2,3-epoxy butane with 2,3-dichloro-5,6-dicyano-1,4-benzo-quinone(DDQ) in trifluoroacetic acid(TFA) gave dibenzocycloheptadienes by pinacol rearrangement and intramolecular oxidative coupling of the aryl groups. Meanwhile, the benzofuran analogues were also formed by the same method. These new lignans have potent CNS inhibitory activities. It has been proven that the method is particularly useful when applied to the substrates in which the ring substituents are electron donating. The structures of these products were identified by the MS, UV, IR, NMR spectra, and elemental and X-ray crystallographic analyses.     

Conformational control of selectivity in the dienone-phenol rearrangement

We have explored the dienone-phenol rearrangement of substrates where: only the p-cresol pathway is possible and relative migratory aptitudes should play no role in determining the regiochemistry of the reaction. For these substrates the selectivity of the rearrangement was found to depend on the stereochemistry of the spirocyclic intermediate formed during the course of the rearrangement. Rearrangement of one of these substrates gave—surprisingly—a single regioisomeric product. Selectivity in this case can be correlated with the relative stability of cationic intermediates, which lie on the pathway between spirocycle and final product.     

Addition/oxidative rearrangement of 3-furfurals and 3-furyl imines: new approaches to substituted furans and pyrroles

Furans and pyrroles are important synthons in chemical synthesis and are commonly found in natural products, pharmaceutical agents, and materials. Introduced herein are three methods to prepare 2-substituted 3-furfurals starting from 3-furfural, 3-bromofuran, and 3-vinylfurans. Addition of a variety of organolithium, Grignard, and organozinc reagents (M-R) to 3-furfural provides 3-furyl alcohols in high yields. Treatment of these intermediates with NBS initiates a novel oxidative rearrangement that results in the installation of the R group in the 2 position of the 2-substituted 3-furfurals. Likewise, metalation of 3-bromofuran with n-BuLi and addition to benzaldehyde provides a furyl alcohol that is converted to 2-phenyl 3-furfural upon oxidative rearrangement. Enantioenriched disubstituted furans can be prepared starting with the Sharpless asymmetric dihydroxylation of 3-vinylfurans. The resulting enantioenriched diols undergo the oxidative rearrangement to furnish enantioenriched 2-substituted 3-furfurals with excellent transfer of asymmetry. This later method has been applied to the enantioselective preparation of an intermediate in Honda's synthesis of the natural product (-)-canadensolide. Mechanistic studies involving deuterium-labeled furyl alcohol suggest that the oxidative rearrangement proceeds through an unsaturated 1,4-dialdehyde intermediate. The alcohol then cyclizes onto an aldehyde, resulting in the elimination of water and rearomatization. On the basis of this proposed mechanism, we found that 3-furyl imines undergo the addition of organometallic reagents to provide furyl sulfonamides. Under the oxidative rearrangement conditions, 2-substituted 3-formyl pyrroles are formed, providing a novel route to these heterocycles. In contrast to the metalation of heterocycles, which often lead to mixtures of regioisomeric products, these new oxidative rearrangements of furyl alcohols and furyl sulfonamides generate only one regioisomer in each case.     

Synthesis and reactivity of bicyclo[3.2.1]octanoid-derived cyclopropanes

Photochemical oxa-di-π-methane rearrangement of bicyclo[3.2.1]octanoid scaffolds affords multifunctional, donor-acceptor cyclopropanes. A related photochemical reaction of an iminium ether substrate uncovered an unprecedented aza-di-π-methane rearrangement of a β,γ-unsaturated iminium. Donor-acceptor cyclopropanes have been evaluated as substrates for reactions generating several new chemotypes.     

β-Dicarbonyl compounds

Summary The presence of alkali suppresses the oxidative rearrangement of 2-acylcycloalkanones and favors the process of oxidative cleavage which occurs simultaneously.     

Synthetic route to 4-(2-aminoethyl)-5-hydroxyindole derivatives

In synthetic studies leading to the title compounds, application of the Claisen rearrangement of 5-allyloxyindole was investigated. Almost quantitative yields of Claisen rearrangement product were realized, and a strategy for oxidative cleavage of the allyl double bond to an indole-4-acetaldehyde derivative was developed. A new method for conversion of 2,3-dihydroindoles into indoles was utilized: air oxidation in a strongly basic environment. The Claisen rearrangement of allyloxyindoles is presented as a method having considerable potential utility in synthesis of a variety of polysubstituted indoles.     

An improved procedure for the Beckmann rearrangement of cyclobutanones

γ-Lactams are important building blocks for the synthesis of biologically active molecules and can easily be accessed via Beckmann rearrangement of cyclobutanones. However, Beckmann fragmentation is often a competing reaction for these strained ketones. We found that performing the Beckmann rearrangement with Tamura’s reagent in the presence of aqueous HCl suppresses the undesired fragmentation reaction. This improved procedure was applied to a broad scope of substrates affording monocyclic, bicyclic, tricyclic or spirocyclic lactams.Our experimental results and DFT calculations suggest that the mechanism of the rearrangement probably involves a tetrahedral intermediate and doesn’t proceed via oxime fragmentation as in a classical Beckmann rearrangement.     

Synthetic studies on isoschizogamine: construction of [3.3.1] bicyclic aminal core by using oxidative skeletal rearrangement

The tetracyclic core structure of isoschizogamine containing aminal functionality was constructed by oxidative skeletal rearrangement of a 1,2-diaminoethene derivative. The 1,2-diaminoethane was prepared by palladium-catalyzed allylation at the 4a position of a 1,2,3,4-tetrahydro-β-carboline derivative and subsequent lactam formation. After the oxidative skeletal rearrangement using dimethyldioxirane, the allyl group was removed by a three-step sequence to provide the tetracyclic core skeleton of isoschizogamine with aminal functionality.     

Synthetic studies directed toward guianolides: an organoiron route to the 5,7,5 tricyclic ring system

A diastereoselective route to the 5,7,5-tricyclic core of the guianolides is presented. This route relies on Cope rearrangement of a divinylcyclopropane prepared by alkenyl Grignard addition to a (pentadienyl)iron(+1) cation, followed by oxidative decomplexation. An additional key reaction involves oxidative rearrangement of a 3,4-epoxy-1,7-diol to generate a γ-lactone. The relative stereochemistry of this product was established by X-ray crystallography.     

Cyanuric chloride catalyzed Beckmann rearrangement of ketoximes in biodegradable ionic liquids

Imidazolium-based ionic liquids (ILs) containing ester moieties in the side chain were successfully used as an alternative to traditional ILs in the Beckmann rearrangement of ketoximes catalyzed by 2,4,6-trichloro[1,3,5]triazine. The procedure is mild and suitable for both aromatic and cycloaliphatic substrates affording the rearrangement products in good to quantitative yields. The process is eco-sustainable since these ILs are biodegradable and in addition they can be recovered and reused.     

Ireland-Claisen rearrangement of ynamides: stereocontrolled synthesis of 2-amidodienes

The Ireland-Claisen rearrangement of propargyl ynamido ester substrates is reported. The expected allenamide carboxylic acid products from [3,3]-sigmatropic rearrangement are not isolated, with 2-amidodienes alternatively formed in good yield with high levels of stereocontrol after decarboxylation.     

Oxidative reactions of tetrahydrobenzimidazole derivatives with N-sulfonyloxaziridines

An investigation of the utility of N-sulfonyloxaziridines to effect the oxidative rearrangement of tetrahydrobenzimidazoles to spiro fused 5-imidazolones is reported. In addition to the anticipated rearrangement manifold, it was found that 2-amino substituted derivatives afford products resulting from rearrangement, or alternatively from addition of methanol or water depending on the nature of the N-substituents and reaction conditions.     

An Ireland-Claisen rearrangement approach to β-amino acids

The first use of enamide substrates in an Ireland-Claisen [3,3]-sigmatropic rearrangement reaction is presented as a novel route to complex β^2,3-amino acids     

Synthesis and Lewis acid catalyzed Claisen rearrangement of 2-(1,3-oxazolin-2-yl)-substituted allyl vinyl ethers

Allyl vinyl ethers containing an acceptor function in the 2-position are useful substrates for the Lewis acid-catalyzed Claisen rearrangement. The first synthesis of acyclic 2-(1,3-oxazolin-2-yl)-substituted allyl vinyl ethers is reported. The Lewis acid catalyzed Claisen rearrangement of these allyl vinyl ethers afforded the rearrangement products with low to moderate diastereo- and enantioselectivity. The catalyzed rearrangement of chiral allyl vinyl ethers was investigated. The combination of substrate- and catalyst-induced diastereoselectivity led to unexpected and unprecedented results.     

The role of cyclobutenes in gold(I)-catalysed skeletal rearrangement of 1,6-enynes

1,6-Enynes with electron-donating substituents at the alkyne undergo gold(I)-catalysed single cleavage skeletal rearrangement, whereas substrates with electron-withdrawing substituents evolve selectively to double cleavage rearrangement. Theoretical calculations provide a qualitative rationale for these effects, and suggest that bicyclo[3.2.0]hept-5-enes are involved as intermediates. We provide the first X-ray structural evidence for the formation of a product of this class in a cycloisomerisation of a 1,6-enyne.     

An Oxidative Rearrangement of 6‐Phenylbicyclo[3.2.0]heptan‐6‐ol to 1,1′‐Biphenyl‐Carbaldehydes: A Mechanistic Study

Acid‐catalyzed rearrangement of 6‐phenylbicyclo[3.2.0]heptan‐6‐ol gave 1,1′‐biphenyl and 1,1′‐biphenyl‐carbaldehydes in small amounts as well as the expected rearrangement products. A detailed study of the reaction mechanism revealed that the conversion occurs via an oxidative process through the consecutive formation of cycloheptadienes, cycloheptatrienes, and 1,1′‐biphenyls. The acid‐catalyzed rearrangement of 6‐phenylbicyclo[3.2.0]hept‐2‐en‐6‐ols gave 1‐ and 2‐phenylcycloheptatrienes directly, from which 1,1′‐biphenyl and 1,1′‐biphenyl‐carbaldehydes were obtained by oxidation.     

Cerium(IV) ammonium nitrate-mediated oxidative rearrangement of cyclobutanes and oxetanes

A facile CAN-mediated oxidative rearrangement of alkoxyaryl cyclobutanes and oxetanes is described.