Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• in 64% and 58% yield, respectively. Substituted styrenes and 1-ethynylbenzene were also tolerated well, giving corresponding products 3ai–3aj in 45–50% yields. The formations of 3ah–3aj likely derives from an azo-Diels–Alder reaction of styrene or ethynylbenzene with an imine intermediate, in situ

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• [22]. There are not many transformations of aliphatic SF5 compounds described in the literature. Among them are the preparation and derivatization of SF5-aldehydes [23], Diels–Alder reactions [24][25][26], the “click reaction” of SF5-acetylenes with azides to form triazoles [27], and 1,3-dipolar

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• extensive attention [14][15][16]. Also as a five-membered heterocyclic ring, the cycloaddition reaction of N-substituted pyrroles is much less than that of furan [17][18][19][20][21]. As a matter of fact, the Diels–Alder adduct formation of pyrroles with benzyne has been postulated in 1965 as transient

• products under thermal conditions to afford arylamines [22]. Inspired by the pioneering work of Stuart and Wang [12][13], herein we reported the usage of diaryliodonium salts as aryne precursor for Diels–Alder cycloadditions of N-arylpyrroles (Scheme 1d). Results and Discussion We initially started the

• cycloaddition reaction of 1-phenylpyrrole (1a) using phenyl(mesityl)iodonium tosylate (2a) as benzyne precursor. To our delight, with LiHMDS as the base in toluene, the Diels–Alder adduct 3aa was obtained in 23% yield at room temperature (Table 1, entry 1). However, when the reaction temperature was increased

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• syntheses of various pyrimidinones as potentially bioactive products by means of the highly controlled continuous-flow retro-Diels–Alder reaction of condensed pyrimidinone derivatives are presented. Noteworthy, the use of this approach allowed us to rapidly screen a selection of conditions and quickly

• confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved. Keywords: continuous-flow; desulfurisation; norbornene-fused heterocycles; pyrimidinones; retro-Diels

• –Alder reaction; Introduction The continuous-flow (CF) technology has gained significant importance in modern synthetic chemistry [1][2][3] and becomes a core technology in the pharmaceutical, agrochemical, and fine chemical industries [4][5]. The use of this technology opens a new door to a quick

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• CaCO-2. Lin et al. [52] developed the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 via aza-Diels–Alder reaction of pyrazolylimines 43 with maleimides 44 (Scheme 8). Pyrazolylimines 43 were in turn obtained from the reaction of 5-aminopyrazole 16 with diisopropylformamide dimethyl acetal (R

• -arylmaleimides 44 in a solvent-free methodology based on microwave-assisted (80 W, 80 °C, 1.5 h) hetero-Diels–Alder reaction for the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 (Scheme 8). Jiang et al. [54] described the synthesis of macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives 49 by the

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• base to give the σ-adducts. Earlier it was found that an aza analog of DNBF – 4-aza-6-nitrobenzofuroxan (1, ANBF) ranks among the most electrophilic heteroaromatics known to date [17][18]. Compound 1 gives a remarkably stable hydrate in aqueous solution and forms Diels–Alder cycloadduts 2 with dienes

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• structure of Ecm1 which forms a substrate binding cleft rather than a pocket [94]. Vinylbenzyl-modified cap analogues (bearing the modification at either the N7 or N2-position) provided a platform for inverse electron-demand Diels–Alder reactions with tetrazine conjugates and for photo-click reactions using

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

• -Diels–Alder reaction [87]. Coupling between alkynoic acid and 2-aminobenzothiazole and the use of ionic liquids have also been developed [88]. Heterogeneous catalysts such as kaolin and hydrotalcites have been employed in the synthesis of benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones [89][90

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• vinylphosphonium salts can be used in the Diels–Alder reaction with dienes such as isoprene, 1,3-butadiene, 2,3-dimethyl-1,3-butadiene, cyclopentadiene, and 1,3-cyclohexadiene, resulting in cyclic phosphonium salts 115 in yields of 90–96% (Scheme 66) [78]. Gelmi et al. showed that vinylphosphonium bromide 8 in

• )vinylphosphonium salt. Synthesis of 7-oxo-7H-pyrido[1,2,3-cd]perimidine derivative via nucleophilic displacement of the triphenylphosphonium group in intermediate α,β-di(methoxycarbonyl)vinylphosphonium salt. Application of vinylphosphonium salts in the Diels–Alder reaction with dienes. Synthesis of pyrroline

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• laboratory scale with high yields, from affordable, commercially available starting materials. Keywords: [4 + 2] cycloaddition; Diels–Alder; isobenzofuran; trapping reagent; Introduction Isobenzofurans have been described as the most reactive dienes for Diels–Alder reactions [1][2][3][4][5]. Their high

• reactivity is mainly due to the resonance energy gained by formation of a benzene ring in the cycloaddition product (Scheme 1) [6]. Isobenzofurans have been extensively used as 4 electron (diene) components in Diels–Alder reactions, and moreover in other cycloaddition reactions such as [4 + 3], [4 + 4], [8

• the majority of the reported methods is a retro Diels–Alder reaction [6][13][15][16][17]. Fieser and Haddadin [17] describe IBF as a transient intermediate and Warrener and Wege [13][15] isolated IBF at −80 °C on a cold finger. The disadvantages of these methods are high reaction temperatures during

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• cycloaddition, CuAAC and RuAAC), the thiol–yne reaction, Diels–Alder reactions and the Sonogashira cross-coupling. While amino acids with a terminal alkyne in the side chain are well-known, the synthesis of their correlates where the carboxy group is replaced by a terminal alkyne is still tedious. Nevertheless

• acid function of amino acids can be easily converted into amides or esters (Figure 1), propargylamines have been converted into acids, alcohols [12] or olefins in order to obtain natural products like angustureine and cuspareine [13]. Intramolecular Pauson–Khand reaction [14], Diels–Alder reaction [15

• ) Intramolecular Pauson–Khand reaction, R = (S)-tert-butylsulfinyl, R’ = CH2CH2OTBDPS [14]. b) Diels–Alder reaction, R = pTs, R’ = H, R’’ = Me [15]. c) Gold-catalyzed intramolecular reaction to azetidin-3-ones, R = tert-butylsulfonyl, R’ = aromatics, aliphatics [16]. d) Sonogashira cross-coupling, R = tert

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

• product [30] (Scheme 6). The analogous reaction with phenyl vinyl sulfide (22) gave the expected cyclobutane 23 exclusively. However, in the absence of ZnCl2, a mixture of 23 and 3,4-dihydro-2H-pyran 24 was obtained, with the latter compound formed through a competitive hetero-Diels–Alder reaction [30

• isomeric homo-Diels–Alder adducts were found in the mixture. [3 + 2]-Cycloadditions (1,3-dipolar cycloadditions) Electron-rich 1,3-dipoles such as thiocarbonyl S-methanides and azomethine ylides react with dipolarophiles E-1 and Z-1 to give five-membered cycloadducts through stepwise zwitterionic reaction

• changes to non-concerted stepwise processes, which can involve zwitterionic or diradical intermediates. [4 + 2]-Cycloadditions (Diels–Alder reactions) In analogy to reactions with tetracyanoethene (TCNE), the first [4 + 2]-cycloadditions (Diels–Alder reactions) of E-1a were performed using typical 1,3

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• , sultams have been prepared employing Diels–Alder reactions, radical cyclizations, reductions of sulfonylimines, ring-closing metatheses, nucleophilic aromatic substitutions and Heck cyclizations [14][15][16]. Earlier on, our group has developed versatile syntheses of sultams based on the transformation of

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• heterocyclic terpenes by subsequent (hetero)-Diels–Alder or [4 + 1]-cycloadditions with nitrenes is also depicted. Keywords: dimerization; heterocycles; isoprene; monoterpene; palladium catalysis; Introduction The dimerization of conjugated dienes represents a useful, highly atom economic and straightforward

• increase of the reactivity (86% yield), delivering the TT-linear terpene as the main product in a 16:1 ratio of 2-TT vs other dimeric isomers 2, along with Diels–Alder-generated cyclic monoterpene byproducts (Table 1, entry 4). Interestingly, the dimerization did not take place at temperatures below 90 °C

• - and N-heterocycles The different dimers of isoprene can be transformed into a large number of derivatives such as terpene-alcohols or ethers [38]. Moreover, some isoprene dimers have been submitted to Diels–Alder reactions with olefins such as maleic acid anhydride or methacrolein to form products

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• intramolecular Diels–Alder (IMDA) cycloaddition as key step to construct the tetrahydroindane unit (Scheme 1) [7]. An enone, derived from allylic alcohol 8 served as precursor to yield tetrahydroindane 9 with excellent diastereocontrol at −25 °C. The major drawback of our first total synthesis of elansolid B1 (2

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• the synthesis. The cyclization of the linear precursor is usually achieved by utilizing various ring-closing reactions such as Diels–Alder reactions, [15] aldol reactions, [16] copper-catalyzed azide–alkyne cycloaddition, [17][18] macrolactonization, macrolactamizations, Staudinger ligation or

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• ][30]. Although the Ugi-4CR generates linear α-acylamino-amides, a wide range of heterocycles are accessible through the combination with other transformations (post-transformation strategy) [31]. For example, the Ugi/Diels–Alder process leads to the formation of benzofurans and indoles [32] as well as

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• formation [12][13][14], Diels–Alder reaction [15][16] or the imine/oxime condensation [17][18]. These reactions tend to produce strong covalent interactions between the surface and the molecules in solution which ensure a stable immobilization. One limitation of the covalent strategy lies in the

Unpredictable cycloisomerization of 1,11-dien-6-ynes by a common cobalt catalyst

• Abdusalom A. Suleymanov,
• Dmitry V. Vasilyev,
• Valentin V. Novikov,
• Yulia V. Nelyubina and
• Dmitry S. Perekalin

Beilstein J. Org. Chem. 2017, 13, 639–643, doi:10.3762/bjoc.13.62

• formation of meta/para-products of Diels–Alder reactions [28][29][30][31][32], linear/branched products of hydrovinylation reactions [33][34], [2 + 2] cycloadditions vs Alder-ene reactions [35], E/Z isomerizations of alkenes [36][37] and other processes [38][39][40][41][42]. Herein, we report the

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• biscembranoids are believed to originate as products from Diels–Alder cycloaddition between two cembranoid units. Besides methyl sarcoate, only methyl tetrahydrosarcoate and isosarcophytonolide D are reported to act as dienophile (western part) in over 60 described biscembranoids [49]. The western parts in the

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

• neurodegenerative diseases and as effective insecticides, fungicides and herbicides. Keywords: biological activity; Diels–Alder reaction; Friedel–Crafts reaction; 1-indanones; Nazarov reaction; Introduction In the last few years, 1-indanone derivatives and their structural analogues have been widely used in

• provide the biggest number of carbon atoms during the synthesis of the 1-indanone benzene ring. For instance, 1,3-dienes in the Diels–Alder reaction provide 4 carbon atoms of the six ones needed to construct the benzene ring of 1-indanone compared to dienophiles which deliver only two of them. 2.1 From

• 1,3-dienes Wolf and Xu have synthesized 7-methyl substituted 1-indanone 241 utilizing 1,3-pentadiene (238) and 2-cyclopentenone (239) as starting compounds [96]. 7-Methyl substituted 1-indanone 241 has been obtained in the Diels–Alder reaction between 1,3-pentadiene (238) and 2-cyclopentenone (239

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

• to analyze NMR (via Labview software) data and optimize the reaction conditions. They performed a range of reactions including imine formation (Figure 14), electrophilic fluorinations and Diels–Alder reactions. This system was employed to perform kinetic studies, in-line structural characterization

• including DEPT spectra, 2D-NMR spectroscopy, 19F NMR spectroscopy and monitoring of the stereoselectivity in Diels–Alder reactions and self-optimization of flow conditions using a modified version of the Nelder–Mead algorithm. For the NMR integral data for each experiment, the algorithm (Figure 15) selects

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• decyanation reaction depends on the structure of the α-aminonitrile, stereoelectronic effects and internal strain of the molecule [68]. Chuang et al. prepared a set of α-aminoacrylonitriles 11 by a cyano-promoted aza-Diels–Alder cycloaddition [71]. The cyano groups were then removed in high yields by

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• Christian H. Hornung Miguel A. Alvarez-Dieguez Thomas M. Kohl John Tsanaktsidis CSIRO Manufacturing, Bag 10, Clayton South, Victoria 3169, Australia 10.3762/bjoc.13.15 Abstract This work describes the Diels–Alder reaction of the naturally occurring substituted butadiene, myrcene, with a range of

• different naturally occurring and synthetic dienophiles. The synthesis of the Diels–Alder adduct from myrcene and acrylic acid, containing surfactant properties, was scaled-up in a plate-type continuous-flow reactor with a volume of 105 mL to a throughput of 2.79 kg of the final product per day. This

• fragrances are based on myrcene, such as geraniol, nerol, linalool, menthol, citral, citronellol or citronellal [3]. The terminal diene moiety present in myrcene allows for a reaction with a suitable dienophile following the Diels–Alder reaction mechanism. Dahill et al. describe the synthesis of the Diels