A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• involved the synthesis of precursor (+)-198 from phenylacetic acid and (−)-α-PEA via sequential amidation, reduction and Pictet–Spengler cyclization reactions. The key anodic oxidation in the presence of NaCN converted (+)-198 to α-amino nitrile (+)-199 with excellent diastereoselectivity. Upon further

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• bromo substituent of the appropriate substrates 20a or 20b should converted into the respective organomagnesium product by bromine–magnesium exchange. In an expected subsequent Parham-type ring-closing reaction [33] the nucleophilic carbon at position 4 should trap the ester (or nitrile) group to lead

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• -arylated lilolidines were generally obtained in high regioselectivities and in good yields using aryl bromides as easily available aryl sources, acetates as inexpensive bases and PdCl(C3H5)(dppb) as air-stable catalyst. The reaction tolerated a wide variety of useful functional groups such as nitrile

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• -diimidazole or di-2-pyridyl thionocarbonate [57][58]. Decomposition of dithiocarbamate salts or thiocarbamates with various reagents offers a good alternative [59][60][61][62] as well, however, this approach first requires the synthesis of the appropriate precursor. Nitrile oxides react with thiourea to

• afford isothiocyanate and harmless urea [63][64][65], but one should note that the instability of the nitrile oxides leads to many byproducts, turning this approach less attractive. The synthesis of isothiocyanates starting from isonitriles involves sulfur-containing reagents such as thallium

• , we have turned our attention to different benzylic alcohols that could be utilized to further examine the functional group tolerance of the reaction. Notably, chlorine, bromine and iodine substituents were compatible with the transformation, providing 3m, 3n, 3r and 3s in 81–89% yield. The nitrile

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China 10.3762/bjoc.15.143 Abstract Isoxazoline-linked porphyrins have been synthesized by a regioselective 1,3-dipolar cycloaddition reaction between vinylporphyrin 2 and nitrile oxides. The steric interaction directed the

• ; isoxazoline; macrocycles; nitrile oxide; porphyrin; Introduction In nature, porphyrin-type compounds play a prominent role in life [1]. It is well known that certain vital functions, like O2 transport, photosynthesis etc. depend on the action of porphyrin–metal complexes [2][3][4][5]. Inspired by the natural

• -generated nitrile oxide, which showed inferior selectivity and afforded regio-/stereoisomers [43]. NMR analysis assisted the identification of various isomeric isoxazoline-linked chlorin products. Here, we would like to report an artificial vinylporphyrin 2, which has been designed to control the

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• -component reaction, to afford isoindolinones 53 substituted with nitrile or carboxamide groups (Scheme 15, method A) [93]. Trimethylsilylcyanide (52), and benzyl-, alkyl- and allylamines 2 were reacted with 2-formylbenzoic acid (33) in the presence of OSU-6, a mesoporous silica performing as a green Lewis

• acid catalyst for this transformation. At room temperature, the product of this environmentally friendly Strecker reaction is nitrile derivative 53 (R2 = CN, Scheme 15, method A), while at reflux carboxamide 53 (R2 = CONH2, Scheme 15, method A) is obtained. Notoriously, aromatic amines 2 did not work

• oxidation of this radical would give rise to the corresponding cation 74, which would add to the nucleophilic nitrile 70. Intramolecular nucleophilic attack of the carboxy group in 75 followed by rearrangement of intermediate 76 delivered isoindolinone derivatives 71. Ortho-functionalized benzoic acids have

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• CN at 2250 cm−1. In addition, there are characteristic bands at 1664–1668 cm−1, which may include both C=C bond and the exocyclic C=N bond. Fluctuations of endocyclic C=N fragments are observed at 1584 cm−1. Thus, at least one nitrile and one NH2 group are present in the obtained compounds. The 1H

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• -step sequence of oxidation employing ammonium cerium(IV) nitrate (CAN) [20] to afford the corresponding quinone (not shown), followed by reduction with sodium hydrosulfite [21]. With the nitrile in hand, we next attempted to reduce that functional group to an amine to which a leucine moiety could be

• , followed by addition of bromide 5a, potassium phosphate and PdCl2(dppf)2 in DMF at 85 °C for 3.5 h gave the coupled product 10 in 47–63% yields (Scheme 3). In contrast to the case of the Heck coupling products (6 and 8, Scheme 2), nitrile 10 underwent facile reduction with lithium aluminium hydride. The

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• hydrogen in intermediate B, it is possible to form chromonyl-malononitrile conjugated system C and to eliminate the phenylhydrazine. Intermediate C is a highly potent Michael acceptor that may allow the addition of hydrazine to the nitrile group resulting in intermediate D that after elimination of water

• products 5a–d were not formed. The reaction mechanism is shown in Scheme 2. The chemical structures of the products 5a–d are shown in Figure 4. Usually, to activate the nitrile group for cyclization reaction, the existence of Lewis acid, the addition of organolithium reagents or metal

• hexamethylenedisalazane is necessary. However, in this approach, the nucleophilic addition on the nitrile group and the cyclization was achieved without the addition of a catalyst [44]. This reaction possesses a highly atom economical character and requires only triethylamine (40 mol %) as a base in EtOH and provides

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• to β-ketoenamides that are uniquely functionalized alkenes and suitable for a variety of subsequent reactions, in particular in heterocyclic synthesis. This LANCA three-component reaction (LA = lithiated alkoxyallene, N = nitrile, CA = carboxylic acid) was observed for the first time by Oliver Flögel

• in the three-component reaction. The products KE36–39 are derived from the O-protected nitrile obtained from (S)-lactic acid [35][36]. This chiral acid itself was incorporated as third component resulting in β-ketoenamides KE39–41. There is no indication of an erosion of the enantiopurity and the

• reasonable overall yields (Scheme 20) [30]. This pathway via the pyrimidine N-oxides represents a good alternative to the direct oxidation of the 4-methyl group by selenium dioxide (see Scheme 11). The subsequent transformation of the aldehyde PM71 to the oxime followed by dehydration afforded nitrile PM72

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• nitrile functionalities [19][20] have been shown to yield shorter routes to compounds of interest as well as for green chemical applications [21][22]. Hydroxamates belong to a class of valuable biologically relevant compounds of proven record of utility. For example, the hydroxamate SAHA (1, Figure 1) [23

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• –30 °C under argon gas cover during the addition of n-BuLi (1.05 mmol) in hexane (0.47 mL). The created LDA (up to 1.05 mmol) solution was treated with the solid nitrile 1 (200 mg, 0.95 mmol) and stirred further at rt till 1 was completely dissolved, whereupon the carbonyl compound (1.24 mmol, neat or

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• that are generally obtained by the reaction of benzyl halides with appropriate cyanating agents such as KCN [14], TMSCN [15], K4(Fe(CN)6 [16]. Deprotonation of the α-carbon (adjacent to nitrile) by strong bases, especially lithiated ones, resulted in an anionic species that easily undergoes a

• products 4f and 4g, respectively, in a shorter reaction time (Table 2, entries 6 and 7). However, due to the replacement of the nitrile group with hydrogen after decyanation in product 4, the methylenic protons and the methinic proton resonates at around 4–5 ppm as doublets and 5 ppm as pentet

• . Then, the acidic hydrogen adjacent to the nitrile group in the intermediate product is sequentially abstracted by a CN− anion with the extrusion of an HCN molecule and a carbanion alpha to the nitrile group bearing a 1,2,4-oxadiazole ring is formed. The resulted carbanion undergoes a substitution

1,8-Bis(dimethylamino)naphthyl-2-ketimines: Inside vs outside protonation

• A. S. Antonov,
• A. F. Pozharskii,
• P. M. Tolstoy,
• A. Filarowski and
• O. V. Khoroshilova

Beilstein J. Org. Chem. 2018, 14, 2940–2948, doi:10.3762/bjoc.14.273

• Synthesis of DMAN-ortho-ketimines and their cations Target compounds 4a–7a were synthesised by techniques previously developed in our laboratory (Scheme 4) [7][8]. Compounds 4a–6a were obtained by the treatment of the ortho-lithium derivative 8 with the corresponding nitrile (path a). Unfortunately, the

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

• [b]pyridine-3-carbonitrile hybrid heterocycles 7 with an ortho/ortho-para/ortho-meta substituted phenyl ring at C-4 may be attributed to the axial chirality induced in these molecules due to the restricted rotation of the C–C single bond. The steric hindrance exerted between the nitrile group at C-3

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• catalyst or redox catalyst. Various metalloenzymes have been applied in laboratory-scale reactions and a few metalloenzymes such as nitrile hydratase (cobalt(III) in the active site) for the production of acrylamide have found application in industry [25]. Notably, however, the reaction scope of natural

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• found, giving rise to an oxidation wave corresponding to the closed isomer (Figure S23, Supporting Information File 1). Once formed, the closed isomers of both nitrile-substituted compounds, i.e., sDTE66-PhCN and DTE-PhCN, can be reversibly reduced and oxidized (Figure S20 and Figure S23, Supporting

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• terminal part of the LTA from S. pneumoniae. The deprotection of disaccharide 22 to give 27 followed by formation of the trichloroacetimidate 28 proceeded smoothly, as shown in Scheme 6. The following glycosylation using MeCN as solvent relied on the nitrile effect to afford the desired β-anomer 29 in 74

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -hydroxyaryl)pyridine derivatives bearing a carboxylate or a nitrile group suitably placed at C3 position of the aza-ring has been achieved in acceptable chemical yields with a broad functional group tolerance. This sequential C–C/C–N bond making process proceeds through a regioselective allylic alkylation/aza

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• (5 mol %), leading at 20 °C to δ-lactone derivative (±)-15 although with low yield (Scheme 6, Table 4). In continuation, we selected a cyclooctene-fused system, namely isoxazoline (±)-16 which, in turn, was accessed through nitrile–oxide dipolar cycloaddition, by using nitroethane, DMAP and Boc2O

• vacuum and the residue was purified by column chromatography on silica gel (n-hexane/EtOAc). General procedure for the nitrile–oxide cycloaddition To a solution of 1,5-cyclooctadiene (1.5 mmol) in THF (20 mL), EtNO2 (5 equiv), DMAP (0.3 mmol, 20 mol %) and Boc2O (4.5 mmol, 3 equiv) were added and the

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• ], via intramolecular cyclization of a diazomethane group and a nitrile [23], or via our recently reported NH-triazole synthesis starting from 6-methoxyflavanone [24]. Furthermore, 1,4,5-trisubstituted 1,2,3-triazole annulated chromenes have been reported via an intramolecular arylation reaction of 1,2,3

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• followed by a suffix indicating the positively-charged groups has made nomenclature richer and more fluent. IUPAC has given name to several functional groups as protonated species and organyl derivatives thereof: imine–iminium, amide–amidium, nitrile–nitrilium, amine–aminium [34]. In this sense, we propose

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• the corresponding products, which were isolated as methyl esters (Scheme 8). Thus, compound 7 bearing alkyl, ether, ester, and halide substituents exhibited good reactivity. Cinnamonitrile afforded 8f-Me in 81% yield using 10 mol % of catalyst. α-Phenyl-substituted α,β-unsaturated nitrile also reacted

• conditions, the desired carboxylated product 26a was obtained in 75% yield. A variety of arylboronic esters (25b–i) were converted into the corresponding carboxylic acids 26b–i in good-to-high yields. It is noteworthy that ketone, ester, and nitrile functionalities in 26d, 26e, and 26f, respectively, were

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• . Very recently, our group reported on a crown/ammonium rotaxane 17 in which a TTF unit is implemented in the crown-ether wheel (Figure 15) [82]. The rotaxane was synthesized by a catalyst-free nitrile oxide capping strategy in 67% yield. In the neutral state, the wheel is strongly bound to the ammonium