Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• , Aoba-ku, Sendai 980-8578 Japan 10.3762/bjoc.14.172 Abstract A cationic cobalt catalyst efficiently promoted the reaction of N-alkoxycarbonyloxyanilines at 30 °C, affording the corresponding ortho-aminophenols in good to high yields. As reported previously, our mechanistic studies including oxygen-18

• mechanistic studies revealed that the rearrangement of the alkoxycarbonyloxy group proceeded in an unprecedented [1,3]-manner (Scheme 2c). In this article, we describe the overall picture of the intriguing [1,3]-rearrangement reaction, particularly the detail of the reaction, which were not sufficiently

• ]. Further mechanistic studies are underway in our laboratory. Conclusion The cationic cobalt catalysts enabled the rearrangement reaction of N-alkoxycarbonyloxyanilines to proceed under much milder reaction conditions, expanding the substrate scope to more electron-deficient anilines. More importantly, the

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• hypervalent iodine-mediated reactions to achieve the intermolecular oxycarbonylation [79], azidocarbonylation [80] and fluorocarbonylation [81] of alkenes. Mechanistic studies showed that PhI(OAc)2 is activated by the aid of BF3·OEt2 and then reacts with an alkene to form a three-membered iodonium ion

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• in activity. Mechanistic studies substantiated Lewis-acid-catalyzed activation of the epoxide during the reaction. In addition to the asymmetric ring opening of meso-epoxides, other alternative chemical and biocatalytic methodologies have also been explored. Cho and co-workers reported a CBS

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• by weakly-coordinating thiocarbonyl-assisted cobalt catalysis. Thus, carboxylates enabled ferrocene C–H nitrogenations with dioxazolones, featuring ample substrate scope and robust functional group tolerance. Mechanistic studies provided strong support for a facile organometallic C–H activation

• C–H nitrogenation of ferrocenes by weakly-coordinating thiocarbonyls. The carboxylate-assisted cobalt catalysis was characterized by high functional group tolerance and ample substrate scope. Mechanistic studies provided evidence for a facile C–H activation. The C–H amidation was achieved in a

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• this issue of atom-economy, the group of Shafir has reported the metal- and base-free arylation of keto-esters and cyanoketones using [bis(trifluoroacetoxy)iodo]arenes ArI(OCOCF3)2 (Scheme 40) [78]. The reaction can also be applied to cyclic 1,3-diones with equal efficiency [79]. Mechanistic studies

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• by the stereoelectronic interaction between the forming σ(C–Co) bond and a neighboring σ*(C–O) bond. Further mechanistic studies and expansion of the substrate scope, including synthetic applications of this three-component coupling, are currently in progress. Nucleophilic and π-electrophilic

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• as internal alkynes/cycloalkynes taken from literature since its discovery by Huisgen in 1962 up to the current date. Except enumeration of synthetic applications it also covers mechanistic studies, catalysis, effects of substituents and reaction conditions influencing reaction rate and

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• enzymes, nucleases, is one of the underlying biological processes. The remarkable catalytic efficiency of nucleases, together with the ability of ribonucleic acids to serve sometimes as nucleases, has made the cleavage of phosphodiesters a subject of intensive mechanistic studies. In addition to studies

• protein nucleases and ribozymes a subject of intensive mechanistic studies. pH-Rate dependency, X-ray structures, amino acid/nucleotide substitution experiments and the effect of thiosubstitution of phosphate oxygens on the binding of metal ion cofactors have given invaluable information about the

• computational methods [11][12][13][14]. Still, experimental studies with small molecular model compounds play an essential role in mechanistic studies of the enzymatic cleavage of nucleic acids. With small molecules, the importance of various elementary processes, such as proton transfer and metal ion binding

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• mechanistic studies (Scheme 35). First, the key intermediate CF3CuILn is generated in situ by the reaction of TMSCF3 with Cu(II) reagent, followed by transmetalation with activated Ar−H generating the (aryl)CuI(CF3) species C, which might be oxidized to the corresponding (aryl)CuIII(CF3) intermediate D

• . It is desirable to find novel methods to reduce the Cu loadings to catalytic quantities. The preliminary mechanistic studies on the above-mentioned work indicated that CuCF3 was generated in that transformation. It was found that the generation rate of trifluoromethyl anion was much higher than the

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• will involve mechanistic studies and the development of new catalysts to expand the scope of this chemistry. Established methods for the preparation of imines vs this work. Proposed catalytic cycle for quinone-catalyzed deformylation. Studies of quinone-catalyzed C−C bond cleavage in related substrates

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• hours, however, the product was obtained as a mixture of both the syn- and anti-diastereomers. Whilst no mechanistic studies were conducted, it is possible that competing SN1 and/or anchimeric assistance by the benzyloxy group occurred. Work by Schlosser has shown that 1,2-disubstituted epoxide opening

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• versatility of these two reagents have been recently demonstrated through several creative research articles; hence, this review aims to collect the recent progresses in the diverse uses of CF3SO2Na and CF3SO2Cl reagents. A special emphasis is placed on mechanistic studies. The review is divided in Part 1 and

• allowing access to various β-trifluoromethyl ketones 24 featuring aryl, alkyl, functionalised alkyl, alkenyl, acetal, silylated alcohol, pyran, and piperidine functionalities (R group in 24). Mechanistic studies by 19F NMR allowed to identify CF3 complexes of copper(I) and copper(III) and the predominance

• in a sealed tube at 110 °C. Mechanistic studies by electron spin resonance were carried out in which both the CF3• and the β-CF3 alkyl radical intermediate were observed by using 2-methyl-2-nitrosopropane as a radical spin trap. A single-electron oxidative free-radical process was clearly ascertained

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• formyl and hydroxy groups. Preliminary mechanistic studies reveal that a secondary trifluoromethylated alkyl radical is involved in the reaction. Keywords: alkenes; cross-coupling; Heck-type reaction; palladium; secondary trifluoromethylated alkyl bromides; Introduction With the increasing number of

• fluoroalkyl metal species [18][19][20][21][22][23][24]. Recently, we reported a palladium-catalyzed Heck-type reaction of fluoroalkyl bromides, representing an efficient and straightforward alternative to access fluoroalkylated alkenes [25][26][27]. Preliminary mechanistic studies reveal that a fluoroalkyl

• substrate scope and high efficiency. The reaction can also extend to secondary difluoroalkylated alkyl iodide. Preliminary mechanistic studies reveal that a secondary alkyl radical via a SET pathway is involved in the reaction. Results and Discussion We began this study by choosing styrene (1a) and 2-bromo

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• exploration in mechanistic studies of their reactions. Similar to TCNE, these compounds are also attractive Michael acceptors with numerous applications for multistep reactions leading to heterocyclic products. The chemistry of E-1 and Z-1 has not been reviewed, and the goal of the present survey is to

• summarize the methods of their preparation and their applications in organic syntheses. In addition, mechanistic studies of cycloaddition reactions performed with E- and Z-1 will be discussed. Synthesis of dialkyl dicyanofumarates and maleates Numerous methods for the synthesis of E-1 have been reported and

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• mechanochemical reactions. A significant recent advance in mechanistic studies of mechanochemical reaction mechanisms was the introduction of techniques for in situ, real-time monitoring of ball milling processes [27], first through synchrotron X-ray powder diffraction (XRPD) [28][29], and later by Raman

• (Scheme 1). As the Raman signals of both reactants and the quinoxaline product can readily be distinguished, and the product can be obtained in high yield and purity by brief milling (less than an hour), we found this model system to be particularly appealing for mechanistic studies. The milling frequency

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• mechanistic studies suggest that catalyst F1 favours enol formation of starting material 4, thus providing a convincing rational why no base is required for this transformation [79]. Another class of easily accessible electrophilic N-transfer reagents are (aryl)-diazonium salts like compounds 41. The control

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• were obtained with human dermal microvascular endothelial cells (HDMVEC), murine L929 fibroblasts and HeLa cells. Mechanistic studies in a cell-free system then showed that mycolactone efficiently inhibited the co-translational translocation of polypeptides into the ER, while the post-translational

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• previously reported [28]. Presumably, this reaction proceeds via azomethine ylid 6 (Scheme 3); analogous indolium ylids have been used synthetically in 1,3-dipolar cycloadditions [29] and mechanistic studies have been published on the related decarboxylation of pyridinium 2-carboxylates [30]. Fortunately, α

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• organic synthesis and medicinal chemistry. The inside of the reaction mixture has not been studied in depth, but we have begun mechanistic studies. Previous and present approaches. Substrate scope. (All of these reactions were carried out on a 2.0 mmol scale using CH3CN (2.0 mL) as a solvent.) Control

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• that these transformations proceed via a stable sulfonyl-DMAP intermediate [31][32][33][34]. Although many reported mechanistic studies reflect on the unique significance of the para-dialkylamino group [32] to the stabilization of the intermediate, DMAP was never reported to be used as the sole

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• broad applications in studies of chemical and biochemical reaction mechanisms and metabolism pathways. Deuterium is the most common used isotopic label in mechanistic studies. Deuterated organic compounds are widely used in biological [1] and pharmacological [2][3][4][5] investigations. In the last

• intramolecular ring closure [21][22][23][24]. The importance of these cores for medical chemistry studies suggests that isotopically labeled pyrazolo[1,5-a]pyridines and triazolo[1,5-a]pyridines could be of interest. Recently, deuterium-labeled pyridinium-N-imines were applied to mechanistic studies of the

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• in the absence of theoretical or mechanistic studies. Phenylacetylene (7), 1-bromo-4-ethynyl benzene (8) and 1-ethynyl-4-nitrobenzene (9) were hydrogenated using a Pd@C catalyst with trimodal pore-size distribution [152]. The chemoselectivity to the corresponding alkene product showed to follow the

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• significantly, when compared to other reported heteroatom-doping syntheses, the fluorescence of the B-CDs was dynamically quenched by Fe3+ ions. Mechanistic studies suggested that a dynamic quenching model was prevalent at low concentrations due to interactions between Fe3+ and the CD surface, possibly

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• systems for the rapid analysis and optimization of reaction parameters and conditions. The use of this technique in mechanistic studies is also discussed. Review Commercial flow probes NMR spectroscopy is based on the absorption of radiofrequency radiation to produce absorption on the nuclear spin level

• will discuss some recent selected examples of the application of NMR reaction monitoring in flow chemistry. These examples include the design of flow systems, the use of standard NMR instruments and flow probes, the use of microcoils and finally the use of flow-NMR for kinetic and mechanistic studies

• -on-a-chip approach. Kinetic and mechanistic studies The rapid analysis produced in flow NMR can be used for the detection of reactive intermediates and consequently for studying reaction mechanisms and the rapid optimization of a chemical process. The first example was described by Nakakoshi et al

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• followed by anion exchange. The resultant oxocarbenium/tetraphenylborate ion pair undergoes a nucleophilic attack by silyl ketene acetal, which is followed by scavenging the trimethylsilyl cation with a chloride anion to result in chlorotrimethylsilane and the product. Mechanistic studies were conducted to