Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia 10.3762/bjoc.14.269 Abstract The one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitriles, aromatic aldehydes, cycloalkanones and ammonium acetate occurred via a six-step tandem Knoevenagel

• -yl)-3-oxopropanenitrile; tandem reaction; Introduction The syntheses of novel heterocycles through greener protocols have received a great deal of attention of the synthetic organic chemists in view of environmental concerns [1][2][3]. The multicomponent tandem/domino reaction is one among several

• transformation [14][15][16][17][18][19][20][21][22]. Hence, multicomponent tandem reactions minimize the number of steps to synthesize complex heterocycles, avoid the isolation and purification of the intermediates, allow less waste to the environment, shorten the reaction time and are also cost effective

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• presence of the O–H stretching of the -SO3H group at 2650–3550 cm−1 as well as the vibrational modes of N–SO2 and O–SO2 bonds at 1062 cm−1 and 1179 cm−1, respectively. The catalyst 3 was found to be effective in the tandem reaction between β-naphthol (23), aromatic aldehydes 7, and amide derivatives 49 at

• another published article by this research group, silica-supported sulfonated 1,4-diazabicyclo[2.2.2]octane 71 was used for the one-pot tandem Knoevenagel–Michael cyclization reaction between isatin derivatives 32 or acenaphthenquinone (33), barbituric acid derivatives 73, and 1,3-dicarbonyl compounds 20

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• the unwanted isomer [3][4][5][6]. Other asymmetric syntheses of 1 have been reported in the literature. These relied either on organometallic catalysis [7], asymmetric tandem addition to chiral tetrahydronaphthalenes [8], bioenzymatic steps [9] or diastereoselective Evans alkylation from oxazolidinone

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by ¹⁷O NMR spectroscopy

• Nico Santschi,
• Cody Ross Pitts,
• Benson J. Jelier and
• René Verel

Beilstein J. Org. Chem. 2018, 14, 2289–2294, doi:10.3762/bjoc.14.203

• -based group-transfer reagents and provide greater mechanistic insight into reactivity of these reagents (Figure 1). Accordingly, we describe herein how 17O NMR spectroscopy in tandem with gauge-independent atomic orbital (GIAO) calculations may be a viable approach to establishing the predominant

• isotropic shift values (δiso) in tandem with experimental 17O NMR data (δobs) lends credence to the aforementioned structural assignment. Specifically, for the "unassigned" compounds mentioned above, the best R2-value for a linear relationship δobs ~ δiso is obtained when 5 and 6 are assigned as 5b and 6a

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• suitable sensitizer for this reaction. In the case of tricyclic diazodiketones 1d,f (with annulated furan and 2-methylfuran-motifs in their structures), a tandem photochemical process of C–H-insertion followed by cycloelimination of furan from the initially generated hydrazones 2d,f apparently occurs

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• useful for solubilizing the range of analogs included in the study and facilitating product work-up via simple evaporation. High-temperature conditions used a 1:1 t-BuOH/H2O solvent system at 70 °C, identified as useful in a previous study focusing on tandem CuAAC reaction development [35]. Importantly

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• ][26][27][28][29][30]. Over the past years, we have been engaged in the synthesis of novel 1,2,4-triazolo heterocycles annulated to benzoazepine or heteroazepine derivatives by a tandem [3+ + 2]-cycloaddition/rearrangement between 1-aza-2-azoniaallenium ions with nitriles [31][32][33][34]. In the [3

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

• sulfonyl- and phoshoryloxylactonization of alkenoic acids 11 with additional nucleophiles (Scheme 4, bottom) [50], in which a bisamide chiral precatalyst was applied [51]. This reaction provides an efficient access to various interesting enantioenriched γ-lactones through a tandem sequence in acceptable

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• I (30) to its spirocyclic analogue arnottin II (32) by reaction with LiOH followed by PIFA (31). The spirocyclic product arnottin II (32) was isolated in 56% yield (Scheme 7). This approach is based on a tandem oxidative dearomatization process and will be quite useful for the conversion of

• stoichiometric amount of bis(iodoarene) 25 with the terminal oxidant mCPBA in the presence of TsOH·H2O in TFE (Scheme 19). In 2012, Zhao and co-workers [91] developed a new approach for the construction of spirooxindoles 61 through tandem cascade oxidation of substituted anilides 60. In this methodology, anilide

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• the basis of the mechanism the origin of the stereoselectivity is ascribed to the interaction of the Cu ion with the oxazoline oxygen driving the ring-closure step selectively. Keywords: catalysis; DFT calculation; iodonium salts; reaction mechanism; tandem arylation–cyclisation; Introduction

• calculations provided several new chemical insights: deprotonation can take place only after the tandem arylation–cyclisation sequence; the mechanism shows a very limited sensitivity in a wide range of substituents installed on the reactants; a crucial copper–oxygen interaction is responsible for the very high

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• step-by-step structural elucidation of novel G-2 melamine dendrimers based on 4-(n-octyloxy)aniline are reported. Our study demonstrates the crucial influence of the nature (covalent vs ionic) of the dendritic construction in tandem with that of its central building blocks on the aptitude of dendrimers

• amperometric detection. More insights on this debate were obtained by means of DFT calculations only (see section 3.3). 3.3 Assignments by means of 2D-1H-DOSY NMR in tandem with DFT calculations at dendritic level Except for dendrimers 4 (dH 2.45 nm) and 5 (dH 2.48 nm) (Table 3), in the series of trimers 7–9

• realised by covalent and/or (carboxyl/amino) ionic trimerisations, to recommend two G-1 N-substituted melamine dendrons with piperzine-1,4-diyl (linkers) and 4-(n-octyloxyphenyl)amino (peripheral units), D-Cl and D-N

  NH, as promising scaffolds for future dendritic elaborations. Tandem DFT-(VT) NMR

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

• transformations involving stoichiometric amounts of λ3- or λ5-iodanes, thus, has been improved by designing tandem reactions that allows for incorporating the aryl motif into the products through a subsequent one-pot nucleophilic addition or catalytic coupling reaction. This review summarizes the main

• achievements reported in this area. Keywords: atom-economy; couplings; hypervalent iodine; oxidation; tandem reactions; Introduction Synthetic applications of the hypervalent iodine chemistry have grown exponentially in the last four decades as highlighted by several books and comprehensive reviews dedicated

• investigated and significant achievements have been reported making iodine compounds now useful organocatalysts in asymmetric synthesis (reaction 2 in Scheme 1a) [15][16][17][18][19][20][21][22][23][24]. In parallel to these investigations, a third strategy has been envisaged with the development of tandem

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• most appealing as it might allow a tandem arylation and cyclization to reach N-acetylphenoxazine (2) in one pot. The arylations were analyzed by crude 1H NMR yields using an internal standard and revealed that a minor amount of a byproduct was formed along with the expected diaryl ether 3 (Table 1

• recovered starting material was 96%. The limited conversion into product 2 complicated our aim to perform the arylation and cyclization in one pot. The tandem reaction set up depicted in Scheme 6b delivered the O-arylated 3 in 87% yield, rather than product 2, further illustrating the sensitivity of the

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

• stoichiometric waste products once again. The further utilization of this side product in a subsequent reaction step would dramatically increase the AE for such oxidative transformations. A general procedure for such a tandem sequence would involve an initial oxidation step of a substrate A followed by a

• incorporated into the final product, the calculated AE (46% for R1 = R2 = H, R3 = Ar = Ph) is close to the procedures of Panda and Xie due to lower PIDA loadings. A metal-catalysed procedure for the atom-economical utilization of (dicarboxyiodo)benzenes 20 in a tandem C(sp3)–H amination/sila-Sonogashira

• values (66% for 33b) are obtained. In another tandem procedure, a metal-free C(sp3)–H olefination of amidines 34 with DMSO and PIDA derivatives 20b was developed by Namitharan and co-workers [49]. A Pd(II)-catalysed Heck reaction of the formed exocyclic double bond with the emerging iodoarene yields

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• -coupling reactions of substrates containing an 1,3-dithiane moiety are feasible, like in the case of the 2-arylation of 2-aryl-substituted 1,3-dithianes. However, in the case of 2-benzyl-substituted 1,3-dithianes, a tandem elimination/1,3-dithiane ring opening followed by a Pd-catalyzed C−S bond formation

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• challenging tandem hairpin Py/Im polyamides which could recognize >10 base pairs with flexible linker conjugated with a fluorescent dye (either Texas Red (TR) or Cyanine 3 (Cy3)) using a Fmoc-based solid phase synthetic approach; two of the representative conjugates 23 and 24 are shown in the Figure 8 [86][87

• telomere foci clearly because of their fluorescent nature. Later on, the authors successfully designed tandem tetramer Py–Im polyamides with 4 hairpins and 3 hinges targeting 24 bp of the human telomere sequences [88]. Thus, the authors set the new record for the longest binding site of synthetic, non

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• transformations involving tandem reaction sequences [3] and the Ugi–deprotection–cyclization (UDC) strategies [4][5][6][7][8] have been exploited as powerful tools allowing access to biological and pharmaceutical high-value heterocyclic scaffolds [9][10][11]. These reactions are appealing in that they are atom

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• of catalysts in a nanoreactor facilitates one-pot tandem reactions that, in most cases, require two or more incompatible catalysts [22][57]. Catalyst confinement leads to a high local concentration of the substrate at the active site, which results in higher reaction rates and better conversion [9

• conversion of glucose in a tandem reaction [82]. The hydrophilic block of their polymersomes was PEG, and the hydrophobic block contained both poly[2-(diethylamino)ethyl methacrylate] (PDEAEM) which is pH responsive, and poly[4-(3,4-dimethylmaleimido)butyl methacrylate] (PDMIBM) as cross-linker. The activity

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ortho-amidoalkylation of phenols in which a tandem Knoevenagel condensation occurs through o-QM followed by the formation of an unstable oxazine intermediate [64]. Later, the same research group published a similar reaction extended by various lactams carried out in trifluoroacetic acid in water [65

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• the synthesis of other organic scaffolds such as furans and pyridines, via cycloaddition/retro-cycloaddition tandem processes (Figure 1d) [10][11][12][13]. A classical example is the preparation of pyridoxine (a form of vitamin B6) using this approach [14][15]. There are several methods for the

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• rolling circle amplification reaction (RCA) initiated by phi29 DNA polymerase to give a long tandem repeat DNA. As low as 0.4 pM of miRNA could be readily detected with single mismatch specificity [143]. In addition to the direct detection of DNA and RNA targets, the PNA–GO platform has also been used for

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• metal-free method for the synthesis of benzothiophenes via a photocatalyzed tandem addition/cyclization reaction (Scheme 11) [41]. Aryl thiols were coupled with dimethyl acetylenedicarboxylate, applying 9-mesityl-10-methylacridinium perchlorate (Acr+-Mes ClO4−) as organic photocatalyst and benzoic acid

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

• tandem trifluoromethylation/cyclisation processes. Dolbier and co-workers first proposed the use of N-arylacrylamides 3 to access trifluoromethylated 3,3-disubstituted 2-oxindoles 4 under photocatalytic conditions (Scheme 4) [11]. In the presence of Ru(phen)3Cl2 (phen = phenanthroline), a variety of N

• silyl enol ethers. Continuous flow trifluoromethylation of ketones under photoredox catalysis. Trifluoromethylation of enol acetates. Photoredox-catalysed tandem trifluoromethylation/cyclisation of N-arylacrylamides: a route to trifluoromethylated oxindole derivatives. Tandem trifluoromethylation

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