TEMPO/NaIO4-SiO2: a catalytic oxidative rearrangement of tertiary allylic alcohols to beta-substituted alpha,beta-unsaturated ketones

The novel catalytic method for the oxidative rearrangement of tertiary allylic alcohols to beta-substituted alpha,beta-unsaturated ketones is described. TEMPO/NaIO4-SiO2 causes facile and efficient oxidative rearrangement of various acyclic substrates as well as medium-sized and macrocyclic substrates.     

Oxidative conversion of silyl enol ethers to α,β-unsaturated ketones employing oxoammonium salts

The oxidative conversion of silyl enol ethers to α,β-unsaturated ketones using a less-hindered class of oxoammonium salts (AZADO(+)BF(4)(-)) is described. The reaction proceeds via the ene-like addition of oxoammonium salts to silyl enol ethers.     

Oxoammonium salt-mediated oxidative nitriles synthesis from aldehydes with ammonium acetate

An efficient and scalable route for the synthesis of nitriles was developed by oxoammonium salt (4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) mediated oxidative conversion of aldehydes with NH₄OAc. A variety of aliphatic aldehydes as well as benzaldehydes were converted into the corresponding nitriles in high yields. The nitroxyl radical which is the reduced species of the used oxoammonium salt was recovered by simple acid-base extraction for the recycling.     

Mild Metal-Free Tandem α-Alkylation/Cyclization of N-Benzyl Carbamates with Simple Olefins

Easy does it! The chemoselective oxidative α-C(sp(3) )?H alkylation/cyclization reaction of N-benzyl carbamates using simple mono-, di-, and trisubstituted olefins provides functionalized N-heterocycles such as oxazinones. A TEMPO oxoammonium salt serves as the oxidant, making it possible to carry out the reaction at low temperatures. Neither a metal catalyst nor preactivation in the α-position to the nitrogen group are needed.     

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.     

Access to Nitriles from Aldehydes Mediated by an Oxoammonium Salt

A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4‐acetylamino‐2,2,6,6‐tetramethylpiperidine‐1‐oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl‐imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.     

Transition‐Metal‐Free Oxidative Cross‐Coupling of Tetraarylborates to Biaryls Using Organic Oxidants

Readily prepared tetraarylborates undergo selective (cross)‐coupling through oxidation with Bobbitt's salt to give symmetric and unsymmetric biaryls. The organic oxoammonium salt can be used either as a stoichiometric oxidant or as a catalyst in combination with in situ generated NO₂ and molecular oxygen as the terminal oxidant. For selected cases, oxidative coupling is also possible with NO₂/O₂ without any additional nitroxide‐based cocatalyst. Transition‐metal‐free catalytic oxidative ligand cross‐coupling of tetraarylborates is unprecedented and the introduced method provides access to various biaryl and heterobiaryl systems.     

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.     

Olefination of α,α'-divinyl ketones through catalytic Meyer-Schuster rearrangement

The direct olefination of 1,4-dien-3-ones remains a synthetic challenge. A two-step protocol, employing acetylide addition followed by catalytic Meyer-Schuster rearrangement has been developed for the olefination of 1,4-pentadien-3-ones to afford [3]dendralenes. Many of the traditional methods for the Meyer-Schuster rearrangement of alkynyl carbinols are not suitable with these highly unsaturated substrates because of their acid sensitivity. Unexpected reactivity during attempted rearrangement, including Nazarov-type electrocyclizations, is presented, along with conditions to promote the Meyer-Schuster rearrangement of ethoxyacetylene adducts using catalytic VO(acac)(2).     

二烷基苯基磷(膦)酸酯重排和水解反应的结构效应

本文用分子力学(MM)和量子化学(MNDO)方法研究了各种不同磷(膦)酸酯的Csp^2-O-P重排反主尖和碱性水解反应的结构效反应.计算结果表明,随着底物分子中C-P键数目的增多,发生重排反主尖的活化能也增加,这与实验结果完全一致.但由于计算得到的各类磷(膦)酸酯碱性水解反应的活化能同实验结果相矛盾,这可能是由于底物同过渡态之间溶剂化能的差别所致.     

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.     

Mechanism of electrochemical oxidation of spatially hindered amines of 2,2,6,6-tetramethylpiperidine series

Electrooxidation of spatially hindered amines of the series of 2,2,6,6-tetramethylpiperidine in the medium of acetonitrile results in formation of radical cations, aminyl radicals, nitroxyl radicals, and oxoammonium salts identified using the methods of cyclic voltammetry and ESR spectroscopy.     

Reaction of cyclic nitroxides with nitrogen dioxide: the intermediacy of the oxoammonium cations

Piperidine and pyrrolidine nitroxides, such as 2,2,6,6-tetramethylpiperidinoxyl (TPO) and 3-carbamoylproxyl (3-CP), respectively, are cell-permeable stable radicals, which effectively protect cells, tissues, isolated organs, and laboratory animals from radical-induced damage. The kinetics and mechanism of their reactions with .OH, superoxide, and carbon-centered radicals have been extensively studied, but not with .NO2, although the latter is a key intermediate in cellular nitrosative stress. In this research, .NO2 was generated by pulse radiolysis, and its reactions with TPO, 4-OH-TPO, 4-oxo-TPO, and 3-CP were studied by fast kinetic spectroscopy, either directly or by using ferrocyanide or 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate), which effectively scavenge the product of this reaction, the oxoammonium cation. The rate constants for the reactions of .NO2 with these nitroxides were determined to be (7-8) x 10(8) M(-)(1) s(-)(1), independent of the pH over the range 3.9-10.2. These are among the highest rate constants measured for .NO2 and are close to that of the reaction of .NO2 with .NO, that is, 1.1 x 10(9) M(-1) s(-1). The hydroxylamines TPO-H and 4-OH-TPO-H are less reactive toward .NO2, and an upper limit for the rate constant for these reactions was estimated to be 1 x 10(5) M(-1) s(-1). The kinetics results demonstrate that the reaction of nitroxides with .NO2 proceeds via an inner-sphere electron-transfer mechanism to form the respective oxoammonium cation, which is reduced back to the nitroxide through the oxidation of nitrite to .NO2. Hence, the nitroxide slows down the decomposition of .NO2 into nitrite and nitrate and could serve as a reservoir of .NO2 unless the respective oxoammonium is rapidly scavenged by other reductant. This mechanism can contribute toward the protective effect of nitroxides against reactive nitrogen-derived species, although the oxoammonium cations themselves might oxidize essential cellular targets if they are not scavenged by common biological reductants, such as thiols.     

Mechanism of the oxidation of alcohols by oxoammonium cations

The mechanism of the oxidation of primary and secondary alcohols by the oxoammonium cation derived from 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) has been investigated computationally at the B3LYP/6-31+G* level, along with free energies of solvation, using a reaction field model. In basic solution, the reaction involves formation of a complex between the alkoxide anion and the oxoammonium cation in a pre-oxidation equilibrium wherein methoxide leads to a much larger formation constant than isopropoxide. The differences in free energy of activation for the rate-determining hydrogen transfer within the pre-oxidation complexes were small; the differences in complex formation constants lead to a larger rate of reaction for the primary alcohol, as is observed experimentally. In acidic solution, rate-determining hydrogen atom transfer from the alcohol to the oxoammonium cation had a large unfavorable free energy change and would proceed more slowly than is observed. A more likely path involves a hydride transfer that would be more rapid with a secondary alcohol than primary, as is observed. Transition states for this process were located.     

The Dendralenes—a Neglected Group of Highly Unsaturated Hydrocarbons

Dendralenes are acyclic and cyclic cross-conjugated polyolefins derived from 3-methylene-1,4-pentadiene. This review summarizes and compares, for the first time, the methods developed for the synthesis of this class of hydrocarbons. Because of their particular arrangement of π-electrons, the dendralenes are novel substrates for addition and rearrangement reactions, and model compounds for spectroscopic studies.     

The Bellus-Claisen rearrangement

Among the reactions available to synthetic chemists for the construction of new C--C bonds, the Claisen rearrangement is one of the most powerful, elegant, and well-characterized methods. A genuinely new variant, the Bellus-Claisen rearrangement came to light a quarter of a century ago: The reaction of an allylic ether, thioether, or amine with a ketene leads through a [3,3] sigmatropic bond reorganization of a zwitterionic intermediate to an E unsaturated ester, thioester, or amide. When applied to cyclic allylic substrates, a ring-enlargement by four carbon atoms in one step provides medium-ring unsaturated E-configured lactones, thiolactones, and lactams. The scope of the Bellus-Claisen rearrangement and the optimum reaction conditions will be discussed in this Minireview.     

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.     

Gold-catalyzed rearrangement of propargylic tert-butyl carbonates

Diversely substituted 4-alkylidene-1,3-dioxolan-2-ones are efficiently synthesized by a gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates. The substrates are readily accessible and the transformation, which is performed under mild reaction conditions using a low loading of catalyst, allows the synthesis of cyclic carbonates, which would be less efficiently obtained using traditional methods. This procedure has also been applied to the stereoselective synthesis of (E)- or (Z)-4-halomethylene-1,3-dioxolan-2-ones, which proved to be suitable substrates for palladium-catalyzed cross-coupling reactions.     

An oxidative [2,3]-sigmatropic rearrangement of allylic hydrazides

The development of an efficient oxidative [2,3]-sigmatropic rearrangement of allylic hydrazides, via singlet N-nitrene intermediates, is reported. The requisite allylic hydrazide precursors are readily prepared and undergo smooth sigmatropic rearrangement upon exposure to iodosobenzene. The products of this novel transformation are shown to be useful precursors to a variety of compounds.