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

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

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 1136–1138, doi:10.3762/bjoc.13.112

• original article. N/P-doped hollow CDs for efficient drug delivery of doxorubicin. Corrected Scheme 15 of the original article. N/P-doped green-emissive CDs working in tandem with hyaluronic acid-coated AuNPs to monitor hyaluronidase activity. Corrected Scheme 20 of the original article. Different

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• spectroscopy. Liquid chromatography and tandem MS fragmentation studies [21][22][23] are also important additions in deeper structural characterization of CD-oligoester conjugates. The L-LA was reacted with α-, β- and γ-CD (Scheme 1) in bulk at 110 °C in order to ensure a good dispersion of reactants. 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

• provide uniform PL trapping sites on the CD surface, alongside promoting new functionality that can work, in tandem with the core, to turn-on fluorescence. Another example, which highlights the importance of surface passivation and how SPAs can be used to modify and tune CD chemical and physical

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• converted to the corresponding vinylthiazolines 38 through the treatment with dithioic acids 37 in the presence of EDCI in dichloromethane. This transformation is believed to occur through a tandem coupling–cyclization reaction. The authors showed that the treatment of 38 with DBU at 0 °C provided thiazoles

• precursors 31. (a) Microwave-assisted cyclization of N-propargyl thiocarbamate 34. (b) Synthesis of thiazoles 39 through a tandem coupling–cyclization–isomerization sequential process. Synthesis of thiazolidines 42 (42’) from the reaction of β-oxodithioesters 40 (40’) with N-propargylamine (41) through an N

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -promoted α-methylenation of compounds 118 followed by cyclization of the resulting enones 119 allowed to obtain a series of 2-alkyl-1-indanones 120 in very good yields (Scheme 38). A stereoselective, catalytic, tandem transformation of α,β-unsaturated arylketones 121 to fluorine-containing 1-indanone

• in 98% yield for both THP and MOM ethers (Scheme 62). Irradiation of aromatic γ,δ-epoxy ketones 226 with a medium-pressure UV mercury lamp (450 W) led to the formation of 1-indanones 227 via a photochemical epoxy rearrangement and 1,5-biradical cyclization tandem reaction (Scheme 63) [92]. The best

• 276 [106]. The new catalytic reaction which replaced a previously described four-step synthesis [107], involved a tandem aldol condensation/dehydration and cyclization of the intermediate 275 to 276 (Scheme 77). In 1999, Ikeda and Mori have presented a cyclotrimerization of enones (e.g

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• demonstrate the intrinsic epimerase activity of specific non-reducing KRs [87]. In this ‘tandem EIX’ format (Figure 14b), the ketoacyl substrate for the KR to be assayed is generated transiently from the appropriate reduced product by a second, validated non-epimerizing KR, at which point, the intrinsic

• site-directed inactivation of the NADPH-binding site. The tandem assay strategy was also used to try to identify residues potentially participating in the epimerization reaction [88]. This is an intriguing question, as comparative sequence analysis [57][90] fails to reveal any residues which are

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• -(methylamino)phenol (4) to form the corresponding fused polycyclic heterocycle 5. Conditions and limits for the optimisation used in tandem with RD1. Ketone 1 concentration 0.40 mmol/L, semicarbazide concentration 1.20 mmol/L. Supporting Information Supporting Information File 14: General considerations

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• the Passerini reaction for the first time in a sequential multicomponent tandem reaction approach. After evaluation of all possible linker components and a suitable solvent system, highly functionalized dihydropyrimidone–α-acyloxycarboxamide compounds were obtained in good to excellent yields. In a

• reactions, a large number of structurally diverse compounds could be synthesized. In addition, a one-pot Biginelli–Passerini tandem reaction was demonstrated. All products were carefully characterized via 1D and 2D NMR as well as IR and HRMS. Keywords: Biginelli reaction; molecular diversity

• ; multicomponent reactions; Passerini reaction; tandem reactions; Introduction Multicomponent reactions (MCRs) are fascinating straightforward reactions for the preparation of diversely substituted products starting from three or more precursor molecules, forming products containing atoms/moieties of all

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• – Toxicology, Äppelallee 45, 65203 Wiesbaden, Germany 10.3762/bjoc.12.279 Abstract The synthetic cannabinoid MDMB-CHMCZCA was characterized by various spectroscopic techniques including NMR spectroscopy and tandem mass spectrometry. The synthetic sample was found to be of S-configuration by VCD spectroscopy

• samples. For this purpose, we used analytical methods such as NMR, tandem mass spectrometry, vibrational and electronic circular dichroism spectroscopy (VCD and ECD), as well as chiral HPLC. Results and Discussion Pure MDMB-CHMCZCA (3) was obtained as a so-called “research chemical” (RC) from an online RC

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261