Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• ; Introduction Due to the high polarization of the push–pull triple bond, haloacetylenes show high reactivity in nucleophilic substitution reactions. Our systematic studies of the reactions of chloroethynylphosphonates with various nucleophilic reagents have recently revealed a new direction of this reaction

• nucleophilic substitution of chlorine in the chloroethynylphosphonate to form ynamine intermediate A, isomerization of which provides ketenimine B. Further formation of the imine tautomer C enables an intramolecular 5-exo-dig cyclization to furnish the title [1,2,4]triazolo[4,3-a]pyridines (Scheme 6

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

• similar way to that described in Scheme 3. In this case, the coupled alkyne moiety is again activated by Cu(I) and then base-promoted cyclization occurs. A new copper complex formation with the alkene analogue to 13 (see Scheme 3) facilitates the aromatic nucleophilic substitution by indole or pyrrole

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• mesyl chloride in pyridine at 0 °C to give 2-deoxy-1-mesylgalactoheptulose 8 (91%), followed by a nucleophilic substitution reaction with sodium azide in dimethylformamide to give the azide 9 in good yield (90%) [26]. The azide 9 was reacted with a panel of substituted ethynyl arenes to give

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• . Scheme 5 reflects the synthesis of the azo-extended thiomethylpurine 23 starting with the synthesis of hydroxymethylazobenzene 19 [72] in a Baeyer [62]–Mills [63] reaction and subsequent nucleophilic substitution using cyanuric chloride (20) [73] providing chloromethyl azobenzene 21. The introduction of

• photochromic derivatives with varying electronic and thus photochromic properties. The respective arylamines 13a–c were converted into their corresponding hydrazines 14a–c via diazonium-salt formation using sodium nitrite and subsequent reduction using tin(II) chloride [70]. The following nucleophilic

• substitution at a chloro-substituted purine (15a,b) or thienopyrimidine (15c), respectively, and subsequent oxidation of the hydrazine moiety afforded the corresponding azobenzene derivatives 16a–d [71]. Synthesis of azobenzene-extended thiopurine derivatives To further tune the photochromism and compare the

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• developed by Fujita et al. by introducing customized capping reagents for β-CD [10]. Tabushi and co-workers developed a series of capping agents providing 6A,6B-, 6A,6C-, or 6A,6D-selectivity on β-CD (Scheme 1) [11][12]. The cap could be subsequently removed by a suitable nucleophilic substitution to afford

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• -4-oxoquinoline derivative, the aliphatic nucleophilic substitution reaction can be employed, in which the 4-oxoquinoline nucleus acts as an azanucleophile, reacting with different alkyl halides. This reaction leads to products with high yields, and no byproducts are isolated. In this paper we

• and Discussion Synthesis Intermediate 6 was synthesized through the Gould–Jacobs method [24][25][26] and was first subjected to the carbonyl nucleophilic substitution reaction with benzylamine, according to a procedure already described in the literature [15][16]. The isolated carboxamide 5 was then

• verification is, for example, justified by the analysis of the electronic effects, as shown in the Scheme 5. Precisely because it is more unstable, the carboxamide conjugate base is a more reactive nucleophile and, therefore, associated with a lower energy barrier for the nucleophilic substitution reaction

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• activity against Candida albicans and Candida tropicalis [8] and 2-mercapto-1,3-benzothiol and its derivatives exhibit inhibitory effects against thyroid peroxidase [9]. (Hetero)aryl thiols are often prepared from the corresponding halides through direct nucleophilic substitution [10][11][12] or metal

• three-component reaction of o-iodoanilines and K2S in DMSO [20]. Another way to prepare 2-mercaptobenzothiazoles and 2-mercaptobenzoxazoles is the nucleophilic substitution of 2-halo-substituted benzothiazoles and benzoxazoles with sulfur-containing reagents including sodium thiosulfate [21], thiourea

• coupling product 6 [40]. As our previous work shows [23], (hetero)arylthioalkylthiols are easily converted to the corresponding (hetero)arylthiols in the presence of KOH and DMSO through an intramolecular nucleophilic substitution. Conclusion In this work, we developed a facile protocol for the direct

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• Nucleophilic substitution at silicon is already discussed with SN2 mechanism, following a backside attack opposite of the leaving group, as well as a front side attack near the leaving group [62][63][64][65][66][67][68]. A backside attack at the silicon in dichlorosilane 7 and monochlorosilanol 8 is blocked by

• . TIPS: triisopropylsilane. TBDMS: tert-butyldimethylsilane). Hydrogen-bond-catalyzed nucleophilic substitution of 18 with BIFOXSi(OH)2 (9) and nucleophile silyl ketene acetals 11. 18 and 9 form an activated electrophile ion pair complex which yields C–C coupling product 19 (Table 10). Nucleophilic

• substitution of 20 with BIFOXSi(OH)2 (9) and nucleophile silyl ketene acetals 11, 20 and 9 form an activated electrophile ion pair complex which yields C–C coupling product 22 (Table 11). Hydrolysis of BIFOXSiCl2 (7) to BIFOXSi(OH)2 (9) (Scheme 3) in different solvent mixtures, with or without KOH at different

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• precursors for the incorporation in photopharmacophores using cross-coupling, peptide coupling or further functionalization methods such as nucleophilic substitution reaction of the benzyl alcohol 5. The yield determining steps prior to the Baeyer–Mills reaction are the formation of the hydroxylamine with

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• 10.3762/bjoc.14.240 Abstract The direct C–H functionalization methodology has first been applied to perform transition metal-free C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyllithium. This atom- and step-economical approach, based on one-pot reactions of nucleophilic substitution of

• 1-oxide; nucleophilic substitution of hydrogen (SNH); Introduction Dicarbadodecaboranes (carboranes) are known to be 3D polyhedral clusters with a special type of structural organization, relative thermal and chemical stabilities, as well as unique physicochemical properties [1][2][3]. The

• substrates [39][40][41][42], which can be carried out by using SNH reactions (nucleophilic substitution of hydrogen) [43][44][45][46][47][48]. The SNH methodology corresponds to the basic principles of green chemistry [49][50][51][52][53], and it is now considered to be one of the most valuable approaches to

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• reaction sites was quantitatively prepared by the deprotection of 2,2’-OEtBP4 using excess BBr3. The nucleophilic substitution reaction of 2,2’-OHBP4 and ethyl bromoacetate, K2CO3 as the base, afforded 2,2’-COOEtBP4 in 88% yield. The hydrolysis of 2,2’-COOEtBP4 in NaOH solution and then acidification with

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• ][6][7][8][9]. Our group has experience in the synthesis of homothiacalix[n]arenes, a subclass of the thiacalix[n]arenes that has so far received little attention compared to other homoheteracalix[n]arenes [10][11]. Homothiacalix[4]arenes were successfully synthesized via nucleophilic substitution and

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• benzenesulfinate results in the nucleophilic substitution of both the iodine atom and the oxyphthalimide moiety to form a vicinal disulfone 4b. Conclusion Iodo-oxyimidation of vinylarenes using N-hydroxyphthalimide and N-hydroxysuccinimide was developed. PhI(OAc)2 was the best oxidant for the synthesis of the

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• highly explosive [29]. Usually azide groups are installed in the upper rim of the macrocycle by a chloromethylation reaction and subsequent nucleophilic substitution by azide anions [30][31] forming rather flexible azidomethyl fragments. In this investigation more rigid arylazide calixarene derivatives

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• ) condensation b) aromatic nucleophilic substitution reaction, c) deprotection and d) formation of lactate salt. Details of the same are given below: Condensation: Condensation takes place in a first reactor TR1 between the nitrile and hydrazine at high temperature and under pressure. Here, the nitrile was

• using pump P13. Aromatic nucleophilic substitution: The nucleophilic substitution reaction takes place between the pyrazole and N-ethylmorpholine. Pyrazole of step 1 in the extractor was pumped through P13 and N-ethylmorpholine through P3 into the reactor TR2 to form the arylated product of the pyrazole

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

• . Compared to the diverse reactivity profiles of transition metal-catalyzed functionalization of alkenes, hypervalent iodine (III)-mediated reactions are limited to nucleophilic substitution processes. Recently, Liu and co-workers reported a novel cooperative strategy by combining palladium catalysis and

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• % yield. Diazotation followed by nucleophilic substitution with sodium azide gave the desired tetra-azido compound 4 in 56% overall yield from 3. It is noteworthy that the introduction of the azido groups on the calix[4]arene scaffold was clearly confirmed by the presence of an intense band at 2108 cm−1

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• , the dM-Dmoc group is expected to be more stable under nucleophilic conditions, which will allow many transformations including base hydrolysis of esters and amides, hydride reduction of carbonyl compounds, and a wide range of nucleophilic substitution reactions to be carried out without losing the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• important method in the synthetic toolbox for anomeric modification of sugars and glycoconjugate preparation. Left: The Mitsunobu reaction is essentially a nucleophilic substitution of alcohols occurring with inversion of configuration at the alcohol stereocenter. The auxiliary reagents are involved in a

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• , Slovakia 10.3762/bjoc.14.115 Abstract The aromatic nucleophilic substitution reaction based synthesis of a three-armed cryptand displaying 2,4,6-triphenyl-1,3,5-triazine units as caps and pyridine rings in the bridges, along with NMR, MS and molecular modelling-based structural analysis of this compound

• are reported. Appropriate NMR and molecular modelling investigations proved the formation of 1:1 host–guest assemblies between the investigated cryptand and some polynuclear aromatic hydrocarbons or their derivatives. Keywords: aromatic guests; aromatic nucleophilic substitution; cryptand; NMR

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• intermediate (path A). Alternatively, the benzyl radical formed in situ couples with the iodanyl radical to give the pseudo halide, benzyl-λ3-iodane, which is more reactive to nucleophilic substitution by a carboxylic acid [77][78]. Another possible course of the reaction mechanism assumes the formation of a

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• subsequent 5-exo-type cyclization by nucleophilic attack on the iodonium then leads to the isoxazoline or pyrazoline cores (C) bearing the hypervalent iodine(III) group. Following iodine activation by the Lewis acid, the iodonium ion D undergoes nucleophilic substitution with excess acetonitrile to form

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• -catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc). Keywords

• -diethyl tartrate (L-DET) directing the reaction towards the D-galacto-configured epoxythreitol 5a. Alternatively, epoxidation of 4b with D-DET was used to access L-galacto-configured epoxythreitol 5b. A procedure by Miyashita et al. [19] for nucleophilic substitution of epoxides by an azide functionality

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• syntheses have contributed to structural diversity and drug discovery efforts. Convergent and modular approaches to synthesis have garnered much attention in this regard. Among them nucleophilic substitution at C1' has seen wide applications providing flexibility in synthesis, good yields, the ability to

• that is also based on the nucleophilic substitution of ribonolactone. Review Nucleophilic addition to D-ribonolactone and its stereochemistry Two prominent methods of C-nucleoside syntheses involve either i) the linear construction of a (hetero)aryl moiety on a C1'-functionalized ribose or ii) coupling

• ascribed to the modular nature of syntheses that allows for simultaneous alterations in the sugar and the nucleobase to generate diverse analogues in a facile manner. Within this approach, nucleophilic substitution of ribonolactone (Figure 6A) has garnered much attention [61][62][63][69][70][71][72][73][74

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• intermediate. The functionalities required for the secondary transformations like the leaving group (-Cl) for nucleophilic substitution, alkyne and azide for IAAC can be assembled via the Ugi reaction (Scheme 1). Results and Discussion We initiated our studies with the Ugi 4-component reaction of o