Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• ) [44]. The reaction presumably proceeds via an ortho-addition of the λ3-iodane 20b, followed by an iodine-to-oxygen 1,3-aryl migration via a concerted mechanism through the five-membered intermediate TS2 to afford the corresponding diaryl ether 24. A mechanistically similar ortho-iodination/O-arylation

• the stable N-arylated intermediate B via an iodine-to-nitrogen 1,3-phenyl migration. An equilibrium with its enol form B’ is proposed, which affords the aromatization product 28 via H-shift to intermediate C and subsequent dehydroiodination under basic conditions. Although the iodine atom is not

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

•  16, upper part) [57][58]. The reaction proceeds via the formation of the phenyliodinate intermediate 82 followed by a stereoselective 1,2-aryl migration. Elegantly, they utilized the 1,2-aryl migration approach to develop an enantioselective oxidative rearrangement of 1,1-disubstituted olefins 83

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• general, the ‘integrin’ nomenclature was first used in 1987 to describe a family of receptors, appearing as heterodimers of noncovalently associated α and β subunits, able to link the extracellular matrix (ECM) with the intracellular cytoskeleton to mediate cell adhesion, migration and proliferation [42

• carcinogenesis is highly dependent on migration, invasion and angiogenesis renders integrins important anticancer targets. Integrin αvβ3 is an important factor in tumor angiogenesis and metastasis [45], two common characteristics of cancer that discriminates it from other diseases. Notably, integrin αvβ3 (also

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• zinc-dependent metalloprotease that functions in cell proliferation, cell migration and angiogenesis [1][3][4]. However, it is known that the Asn-Gly moiety is subject to Asn deamidation through succinimide formation leading to isoaspartic acid (isoAsp, isoD) and aspartic acid derivatives usually in a

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• alternative to a previously suggested cyclisation of A to a less stable secondary cation, followed by 1,4-hydride migration to yield the same intermediate F [36]. Again, the dihydrobenzene derivative H is not observed, but instead its autoxidation product 14 is detected. Finally, the main product 15 arises

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

• stabilizing a rotamer that favors intramolecular attack of the neighboring hydroxy function on phosphorus, while this kind of acceleration evidently plays a minor role, if any, with ribonucleoside 3´-phosphodiesters. Finally, phosphate migration in 1 takes place between a primary and secondary hydroxy group

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -alkynoates with N-bromosuccinimide (NBS) at rt [34], where those reactions proceed via radical spiro-cyclization and then radical 1,2-carboxyl group migration, were reported. On the other hand, diaryliodonium salts are very useful for the C-arylation of active CH groups, the O-arylation of OH groups, and the

• deprotonation of cation intermediate V occurs to generate 4-aryl-3-bromocoumarin 3 (2nd step). The radical ipso-cyclization of the formed vinyl radical and its 1,2-carboxyl group migration agree with previously reported results [31][32][33][34]. Conclusion The successive treatment of 3-aryl-2-propynoic acids

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• with DIBAl-H to 26 that was converted into the epoxide 27a by Sharpless epoxidation with (+)-L-DET. Treatment with TBSOTf and Hünig’s base resulted in opening of the epoxide with concomitant hydride migration to yield 28a. The stereochemical course for this reaction has been reported by Jung and

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• performed by treatment with Pd(PPh3)4 in the presence of formic acid and butylamine to provide 3’-OH – containing precursor ready for the acylation by the long-chain acyloxyacyl acid. To avoid migration of the phosphotriester group from position 4’ to position 3’ and the formation of the acyloxy-chain

• migration and/or elimination of the secondary acyl chain. TfOH-mediated 1,2-trans glycosylation smoothly provided β(1→6)-linked diglucosamine, the free OH group in position 3 was protected as Alloc carbonate and the benzylidene acetal protecting group was regioselectively reductively opened to furnish 6’-O

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• most widely described type of reactions in which CF3SO2Cl and molecules carrying a C=C double bond are involved are actually cascade reactions that include a cyclisation or a group migration step. In this context, the acrylamide motif was a notably popular object of research, and served in several

• species 7 then underwent an aryl migration/desulfonylation cascade reaction to furnish intermediate 8. In the case of an aryl substituted substrate, this nitrogen radical being stabilised, it directly performed an hydrogen abstraction on acetonitrile to lead to the corresponding α-aryl-β-trifluoromethyl

• -cyanotrifluoromethylations [22] of alkenes under photoredox catalysis. These reactions proceeded through a formyl or a cyano group migration triggered by the addition of the trifluoromethyl radical onto the alkene moiety. Both methodologies were developed using Togni’s hypervalent iodine reagent as the CF3 source, but it

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

• Scheme 10. β-Trifluoromethyl ketones could also be obtained from allylic alcohols 25 by a cascade trifluoromethylation/1,2-aryl migration. Yang, Xia and co-workers employed sodium triflinate under metal-free conditions with ammonium persulfate as the oxidant that was necessary to generate the CF3 radical

• difunctionalisation of unactivated alkenes with CF3SO2Na and an heteroaryl group in which the heteroarylation was realised by a distal heteroaryl ipso-migration was provided in 2017 by Zhu and co-workers (Scheme 32) [54]. A variety of nitrogen containing heteroaryl groups showcased the migratory aptitude selectively

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• with more appropriate N/P ratios (Figure 8b). The results obtained indicate that CD1 has the best binding abilities towards pDNA with respect to CD2 and CD3 (pDNA lacks migration in the gel due to AmCD binding). In fact, CD1 bound the supercoiled conformation of pDNA almost completely at N/P 16.5 and

• the linear one at 38.5. Both, CD2 and CD3 bound the supercoiled conformation of pDNA almost completely at N/P 49.5, the linear one at 38.5 and 27.5, respectively. The lack of RNA migration occurred at N/P 16.5, 27.5 and 16.5 for CD1, CD2 and CD3, respectively. The minimum N/P ratios for complete

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• elimination from 2a, 1,2-migration of the phenyl group, and deprotonation, followed by hydrolysis of the resulting doubly activated benzylic difluoromethylene unit (Scheme 2). Neither a combination of bis(pyridine)iodonium (IPy2BF4) and trifluoromethanesulfonic acid nor a combination of I2 and silver(I

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• -migration of the alkoxycarbonyl moiety to produce the corresponding thiophenes. These reactions represent a new facile one-pot preparative method for the synthesis of 2,4-(diamino)thiophenes from the available reagents. The known findings on the synthesis of (diamino)thiophenes are limited to several

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• ), followed by oxazine-ring opening through olefinic-bond migration (T10) then gives the highly conjugated amino acid ester (±)-11 (Scheme 5). Noteworthy, the presence of DBU in the experiment of (±)-8 with Deoxofluor did not have a significant effect on the ratio of the products. However, in the presence of

• as the expected product, with the ring N-atom in the β-position to the ester group and compound (±)-23, having the N-atom in the γ-position relative to the carboxylate. The latter being formed by N-migration, through an aziridinium ion opening reaction with fluoride. Finally, the fluorination

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• constituent of compounds with diverse applications, some of which display potent cytostatic activity through different mechanisms of action such as DNA intercalation, apoptosis, abrogation of cell migration, inhibition of angiogenesis and disregulation of nuclear receptor signaling [34][35]. Moreover, it was

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• clear evidence that a gem-difluorinated compound had also formed: presumably this was compound 34 arising through neighbouring group participation and migration of the phenyl group [38]. A similar problem was encountered in the synthesis of α,β-difluorinated-γ-amino acids (e.g., 5, Figure 1), which was

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

• elimination of cyanoacetate instead of HCN from the primary adduct 76. The subsequent heterocyclization of 77 occurs via nucleophilic attack of the NH2 group onto the CN group, and H-migration then leads to the products 75. Another class of dinucleophilic reagents rarely used in reactions with E-1 is that of

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• proceeds via base-promoted propargyl–allenyl rearrangement followed by cyclization and allyl migration. Phosphine-substituted indoles can be synthesized by a similar strategy. Keywords: allyl migration; benzothiophene; indole; metal-free; propargyl-allenyl; Introduction Heterocycles are frequently found

• propargyl–allenyl rearrangement [17][18][19][20][21][22][23][24][25][26][27] and an allyl migration [32][33][34] (Scheme 1). In addition, phosphine-substituted indole derivatives could also be conveniently constructed by a similar strategy. This method not only avoids the use of transition metal catalysts

• allyl migration (Scheme 2). Phosphine-substituted indole derivatives were obtained in moderate yield (Figure 3, 4a–c). Conclusion In summary, we have developed an expedient route for the construction of benzothiophene and indole derivatives via propargyl–allene rearrangement and allyl migration. The

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• , the present reaction was proved to take place by an intramolecular process. A reaction mechanism is proposed in Scheme 2, which is similar to that with enones [15]. The monoacylated Breslow intermediate C is formed by addition of thiazolium NHC A to benzil (1a), followed by migration of the benzoyl

• group. Then, this nucleophilic species C reacts with ynones 2 to generate the intermediate D. The second migration of the benzoyl group to the α-position of 2 and simultaneous elimination of A affords product 4. According to the intramolecular mechanism shown in Scheme 2, the two benzoyl groups of 1a

• NHC followed by migration of one neighboring acyl group to the central carbonyl oxygen would generate bisacylated Breslow intermediate 10 (Scheme 5). If this species behaves in a similar manner as the monoacylated intermediate C derived from 1,2-diketone 1, its reaction with enone 6a would be expected

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• . F′ or D′ undergoes H-migration to generate 29 and 30, respectively, along with DDQ-H2. A further investigation revealed that path b is the preferred pathway for this transformation (Scheme 7) [41]. An economical and simple procedure for the oxidative dehydrogenation is demonstrated by the usage of

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

• triggering uncontrolled ARP2/3-mediated assembly of actin. As a consequence, mycolactone A/B causes impaired cell adhesion and defects in the migration of epithelial cells (e.g., increased cell motility accompanied by a loss of directionality). Mycolactone binding to WASP was also demonstrated by means of a

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• into the functional group it next reacts with. The intermediate D can be regarded as the common precursor for the parallel formation of the observed products, 23 by dissociation from the Pt catalyst and proton migration from the sulfonamide to the alcoholate, and 22 by a cascade of electron movements

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• a multitude of biological activities. The most famous representative of this family, cycloheximide (5), has been used for decades as an inhibitor of eukaryotic translation elongation [1][2][3]. Other members of this family show potent cell migration inhibition and antiviral activity [4][5][6], which

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• equiv) in DMF solution and ICI as the promoter (3 equiv) in n-PrOH and was subjected to an oxidative 1,2-aryl migration. The reaction is carried out in a coiled reactor at 90 °C and 1 min residence time. The outlet stream is subjected to an alkaline solution of 2-mercaptoethanol, which quenched the ICI