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

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• bicarbonate bases, direct bromination of the α-carbon does not occur. Instead, the Br is shuttled to the α-carbon by its coupling partner. With this tandem bromination and cyclization strategy, there is no need to presynthesize substrates, thus reducing the number of synthetic steps, time, chemicals and

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

• products (tandem reactions). These reactions occur through an initial formation of the Michael-type adduct followed by a heterocyclization step upon involvement of either a cyano or an ester group as a second electrophilic center. Hydrazine is a powerful dinucleophile and reacts easily with E-1 in ethanol

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• indolactam-based alkaloids 84 (activators of protein kinase C) as shown in Scheme 30. Employing the same strategy, Webb [76] and Resnick [77] prepared analogues of teleocidin and later Quick [78] accomplished the synthesis of indolactam V. Tandem C-nucleophile addition/cyclization processes involving

• ) followed by a formal [4 + 1]-annulation reaction with ylide (tandem Michael addition/intramolecular nucleophilic substitution of dimethylsulfide by oximate anion in intermediate 94). The addition of sulfonium ylides to nitrosoalkenes can end up not only with cyclic products, but also with α,β-unsaturated

• reagents; (3) the elaboration of tandem and domino-processes utilizing conjugate addition of C-nucleophiles to nitrosoalkenes and finally, (4) the design of catalytic enantioselective versions of the Michael addition to nitrosoalkenes (for advances in catalytic asymmetric cycloadditions of nitrosoalkenes

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

• spectroscopy [30] or by a tandem technique combining these two techniques [31]. Whereas valuable mechanistic information on the course of a milling reaction can be obtained through stepwise, ex situ monitoring [32] based on periodically interrupting the milling process followed by sample extraction and

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• (II) acetate-catalyzed aerobic oxidative amination and it proceeds through a tandem Michael addition followed by an intramolecular oxidative amination. Therefore, our target molecules A could be synthesized by the oxidative coupling of 2-aminopyridines with α,β-unsaturated ketones B, themselves easily

• % yield (Table 2, entry 1). Having these optimized conditions in hand, and to explore the substrate scope, different substituted 2-aminopyridines were successfully employed to afford the tandem oxidative cyclization products 7 in 32–65% yields. On the other hand, enones 6 with two different R groups

• (Table 2, entries 1, 2, 3, 6, 8, and 9) were well tolerated under the optimized conditions affording the tandem products 7 in fair to moderate yields, although lower yields were obtained in the cases of 7j and 7g (32% and 36%, respectively). Moreover, two other important heterocyclic frameworks, imidazo

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• efforts in exploring enaminone C(sp2)–H bond sulfenylation [40][41] reactions have led us to establish the synthesis of 3-sulfenylated chromones via KIO3-catalyzed tandem reactions of o-hydroxylphenylenaminone and thiophenols via tandem C–H sulfenylation and intramolecular C–N bond oxygenation (B, Scheme

• protocol toward these compounds through the tandem reactions between o-hydroxyphenylenaminones and sulfonyl hydrazines. In this method, the construction of the target products is furnished via the key C–H sulfenylation without using any transition metal catalyst or oxidative additive. Results and

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• .13.197 Abstract The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction

• combined X-ray diffraction and Raman spectroscopy measurements in a tandem approach. Our investigations reveal that the formation of the crystalline product begins after 36 min and is completed after 50 min. The reaction can be described as a melt-mediated reaction since malononitrile melts during the

• single crystal determination. The crystal structure could be solved, matching the parameters described in the literature [26]. Conclusion Using an in situ tandem approach combining synchrotron X-ray powder diffraction and Raman spectroscopy, we investigated the mechanochemical Knoevenagel condensation of

Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al₂O₃/MeSO₃H

• Hashem Sharghi,
• Mahdi Aberi,
• Mohsen Khataminejad and
• Pezhman Shiri

Beilstein J. Org. Chem. 2017, 13, 1977–1981, doi:10.3762/bjoc.13.193

• , expensive catalyst and low regioselectivity in some cases. One current area of modern synthetic organic chemistry is the development of powerful and effective practical procedures that minimize the requisite time, temperature, labour, and cost for the desired transformations [12][13]. The tandem reaction of

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 reaction efficiency was much lower than that of benzil (1a) (Scheme 4). The only isolated by-product in the reaction of 5a was bicyclo[3.2.1]octanone 8 (ca. 10%), which was formed by competitive tandem Michael–aldol reaction [21]. Cycloheptane-1,2-dione (5b) and cyclododecane-1,2-dione (5c) gave

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• other hand, and in order to further explore the scope of the PVP-Pd NPs catalyst, the synthesis of stilbene derivatives by Pd-tandem reactions was carried out. Some synthetic methods employing consecutive Pd Hiyama–Heck coupling reactions have been reported to obtain a variety of stilbene derivatives

• PVP-Pd NPs maintain their catalytic activity after an initial little drop for at least five cycles. Moreover, the PVP-Pd NPs catalyst system was applied to a tandem Stille–Heck reaction. Experimental Materials and methods 4-Bromoacetophenone (1a), 4-bromobenzophenone (1b), 3-bromoquinoline (1c) 1

• : 10 min; 2º cycle: 20 min; 3º cycle: 30 min, 4º cycle: 30 min, 5º cycle: 30 min. Synthesis of (E)-pterostilbene (19) catalyzed by PVP-Pd NPs. Reaction condition optimizations.a Mizoroki–Heck reaction of aryl halides with olefins catalyzed by PVP-Pd NPs.a Stille–Heck tandem reaction of aryl halides

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

• (Scheme 24). Ruthenium catalysts have also been used under aerobic conditions for oxidative dehydrogenation of heterocycles. For example Lingayya et al. demonstrated that ruthenium chloride (p-cumene)2 [RuCl2(p-cumene)2] catalyzed tandem reaction involving oxidative dehydrogenation, cross coupling and

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

• originally been proposed by the Small group (11, Figure 3) after partial TLC purification and subsequent high-resolution mass spectrometry and 1H NMR spectroscopy (although no NMR data are shown in their report) [50]. Shortly afterwards, the Leadlay group proposed structure 6 (Figure 2) based on tandem mass

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• other is an Au-catalyzed tandem oxazole synthesis using a primary amide, aldehyde, and alkyne [18]. These methods are reasonable for the synthesis of diverse libraries of trisubstituted oxazoles because the combination of three starting materials that are corresponding to the substituents can be readily

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• BASF SE, 67056 Ludwigshafen, Germany 10.3762/bjoc.13.140 Abstract Two hitherto unknown fusaricidins were obtained from fermentation broths of three Paenibacillus strains. After structure elucidation based on tandem mass spectrometry and NMR spectroscopy, fusaricidin E was synthesized to confirm the

• H–C interactions, these resonances were assigned to the β-CH2 group of asparagine (Asn) in the lower homologue 2. Thus, the conclusion was supported by reported data for Asn in other fusaricidins [9] in conjunction to fragments obtained from the tandem mass of the parent peak at m/z 961.6 (Figure 3

• was performed with extensive NMR spectroscopy and tandem mass spectrometry. The full stereostructure of the major component, fusaricidin E, could be confirmed by total synthesis. It included a macrolactamization approach combined with a late stage attachment of the GHPD side chain which was

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• nucleosides [23][24]. The enzymes typically employed for these purposes are nucleoside phosphorylases (NPs) or nucleoside deoxyribosyltransferases (NDTs) in the presence of inorganic phosphate in a tandem enzymatic process [25]. In Scheme 5 we highlight a very recent example of this methodology for the