Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• sulfonyl fluorides in biological applications has been on the increase as evidenced by the number of recent publications [1][2][3]. One potential application of sulfonyl fluorides is as an 18F-radiolabelled synthon that can be conjugated to macromolecules and used to image cancer and other diseases in 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

• fact that in the large – kilogram – scale production of the key synthon 6-monotosyl-β-CD besides the desired product, over-tosylation occurs giving a mixture of regioisomers of ditosylated and tritosylated β-CDs. The ditosylated fraction represents a significant amount (10–20%) of the crude product

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• ) of polyaminoazide mixtures, which were in turn used for the preparation of CaNSs materials with pH-tunable properties, by reaction with the (5,11,17,23-tetra(tert-butyl))-(25,26,27,28-tetrakis(propargyloxy)calix[4]arene (Ca) under the CuAAC reaction conditions. In turn, the synthon Ca is obtained by

Gold-catalyzed ethylene cyclopropanation

• Silvia G. Rull,
• Andrea Olmos and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2019, 15, 67–71, doi:10.3762/bjoc.15.7

• additives [11], alkylating reagent in the Friedel–Crafts synthesis of indanones [12] or as synthon toward the introduction of cyclopropyl moieties in compounds with medicinal or biological interest [13][14]. In view of the lack of examples of direct conversions of ethylene into cyclopropanecarboxylates, and

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• than originally reported are lacking. With an emerging interest in the 4-imino-1,2,3-triazole motif as coordination chemistry synthon, motivation for revisiting the ring degenerate rearrangements first described by L’abbe is twofold. A better understanding of parameters suppressing this rearrangement

• was undertaken. With a secondary aim of identifying improved reaction conditions for exploiting this rearrangement as an efficient synthetic tool for formyltriazole preparations, it was proposed that 1a might display significant advantages over previously utilized 1c [30][31][32][42] as a synthon for

• useful synthon for formyltriazole preparations, it was used to prepare analogs 1c (59% isolated yield) and 1d (64% isolated yield) by the kinetic assay conditions (see Supporting Information File 1). Optimizing of reaction yields and exploring of the scope of amine reagents tolerated by this

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• organic synthesis viewpoint, both CyNSs and CyCaNSs are “artificial” materials, in the sense that they derive from chemical manipulation of a natural occurring starting synthon, namely the cyclodextrin unit. We reasoned that it could be very interesting to explore the possibility of obtaining an entirely

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• provide a useful rigid structure. During the course of our project on the exploitation of dimethyl dibromoadipate as a synthon to access original molecules [13][14], we thought that it could provide an original access to the DKP Pro–Pro framework. More specifically, this type of framework has been used as

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• developed an efficient method for the synthesis of a C12-aminoalditol H2NCH2–(CHOBn)10–CH2OH 10. The chemical reactivity of this valuable synthon was demonstrated by its high yielding coupling with the C-6 position of a selectively protected sucrose by a reductive amination reaction. Experimental General

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• : corrugated chains of head-to-head or head-to-tail aligned molecules and discrete centrosymmetric dimers based on the R22(8) supramolecular synthon in the case of sterically hindered thioureas (Figure 2). The crystal structures of N,N'-diarylthioureas linked in chains via N–H···S hydrogen bonds can further be

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

• facilitate a variety of quinazolinones 44 (Scheme 12) [47]. N-Alkyl benzamides 44´ were also synthesized with this protocol. The average yield ranged from 30 to 92%. Other than methyl(hetero)arenes dimethylamides were also used as C-synthon for such intermolecular annulation to afford unsubstituted

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• N-bromosuccinimide (NBS) as an activator. The coupling efficiency was high (98%) on using 2.5 equiv of the H-phosphonate synthon and 5 equiv of the activator. After each coupling step, the support was precipitated from Et2O and recrystallized from MeCN/Et2O. The unreacted hydroxy groups were capped

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• cross-coupling reactions, cycloaddition reactions, radical reactions and reductive addition reactions. A terminal alkyne can also react as nucleophile or serve as synthon for pyrrole rings [24][25]. Thus we here fuse the rich alkyne chemistry to the EDOT backbone, resulting in a novel EDOT derivative

• , the 3-(EDOT)prop-1-yne (pyEDOT, 3). pyEDOT provides a useful synthon for the synthesis of a variety of EDOT-based polymerizable building blocks. This new EDOT functionalization strategy (Scheme 1), including the polymerization of the resulting building blocks, we illustrate by introducing two examples

• on a glassy carbon electrode, giving a robust electroactive film. Additionally, we show that alkyne-PEDOT can also be post-functionalized in a “click” fashion. All of these proved the synthetic and electrochemical utilities of pyEDOT. Thus, we believe that the pyEDOT synthon provides valuable

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• nitroso dienophiles with masked o-benzoquinones [128]. For instance, they synthesized synthon 152 from 2-methoxyphenol (150) and the chiral auxiliary 151 with 99% de, which was further utilized for the synthesis of (+)-conduramine E-1 (153, Scheme 30). The hetero-Diels–Alder reaction of chloronitroso

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• diallylation; Introduction The norbornene moiety is a useful template and also a versatile synthon in organic synthesis [1]. The double bond present in the norbornene frame is strained and therefore participates in cycloaddition sequences as a C2-synthon [2][3]. It was reported that the norbornene system is

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• (Scheme 1, bottom) as a useful synthon, as it is readily accessible from prenol using our original bromochlorination protocol [7]. In a forward sense, this intermediate could be coupled with a vinyl organometallic to introduce the remainder of the carbon skeleton of 1. While we have achieved moderate

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• results, we decided to synthesize TFOs directly by solid-phase synthesis using a 3'-terminal synthon possessing an alkyne group [30] in order to avoid additional post-synthetic reactions and formation of side products. Also we decided to profit from pH-independent triplex formation by antiparallel TINA

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• the dialdehyde 5 this procedure failed to give the expected Wittig adduct. Whatever the origin of this problem, we decided to explore a new strategy based on a more nucleophilic deuterated synthon. In this regard we targeted prop-1-en-2-yllithium-d5 (15) which is easily accessible through the Shapiro

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin

• Matthias Bender,
• Henrik Mouritsen and
• Jens Christoffers

Beilstein J. Org. Chem. 2016, 12, 912–917, doi:10.3762/bjoc.12.89

• 3 as C-ring synthon. The first report by Ashton et al. [14][15] used N-(D-ribityl)-3-hydroxyaniline (2) as A-ring fragment. The second report by Yoneda et al. [16][17][18] employed 4-benzyloxy-2-chlorobenzaldehyde (4) as building block for the A-ring. Both syntheses suffer from several drawbacks

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• carboxyaldehyde 15. Employment of a Darzens condensation followed by bromination was considered for further elaboration of 15 to 16. For the synthesis of key synthon 12 (Scheme 2), we started from cyclohexenone 19, which was prepared by base-catalyzed condensation of methyl acetoacetate with methyl crotonate [24

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• investigated both the possible synthetic strategies (pathways A and B, Figure 2) in which the phosphate group (or its synthon) has been attached either on the end of the N1-pentyl chain (precursor A) or on the 5’-ribose position (precursor B). At first, to obtain the cpIMP (4) we followed the synthetic pathway

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• alternative feedstock for the production of many of the chemicals we have come to rely on [6][7][8][9][10][11]. Chemical processes that employ CO2 as a synthon for the production of commodity chemicals may form the basis of a sustainable carbon economy. The benefits notwhithstanding, chemical conversion of

Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Mukesh E. Shirbhate

Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165

• cyclophane 1 containing the thiophene and indole moieties is shown in Figure 1. Here, we conceived thiophene-containing diolefin 3 as a possible synthon to assemble the target molecule 1 via 2. Route A involves an RCM of 3 followed by Fischer indolization of 2 (Figure 1). Alternatively, Fischer indolization

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• target molecule 1 is shown in Figure 1. RRM of the tricyclic allylated compound 2 can deliver the target lactam 1. The key synthon 2 can be derived by allylation of lactam 3, which in turn can be prepared via BR starting with the known enone 4 [25][26][27], derived from dicyclopentadiene (5) [28][29][30

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• activated uridine [31], because the triazolyl derivatives are known being stable enough to allow convenient handling and isolation, and they have shown very good reactivity with aliphatic amines. Synthon 3 could be isolated by recrystallization in 76% yield. Next, we introduced a short linker to the N4

• , which was coupled with synthon 12 in anhydrous THF in the presence of 5-benzylmercapto-1H-tetrazole (BMT) as activator (Figure 5). The coupling product 16 was isolated with a yield of 28%. Finally, all remaining protecting groups were cleaved off. The base-labile β-cyanoethyl (CE) group was removed by

• Information File 1). Retrosynthetic analysis of the bifunctional cytidine derivative 1 for functionalization of a periodate-oxidized RNA library. Introduction of the triazolyl moiety into the uridine derivative 7 generating synthon 3. I: 4 equiv POCl3, 16 equiv triazole, 20 equiv NEt3, MeCN, 60 min at 0 °C

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• = pulse length for bipolar pulses. All diffusion spectra were processed in Mat NMR [47]. Glycodendrimer synthesis Procedure A: multiple CuAAc couplings on polypropargylated cores To a solution of polypropargylated core (1.00 equiv) and complementary azido synthon (1.25 equiv/propargyl) in a THF/H2O

• solution of phloroglucinol (13, 10.0 mg, 79.3 μmol, 1.00 equiv) in anhydrous DMF (3 mL) was added under nitrogen anhydrous K2CO3 (previously heated at 250 °C under vaccum, 39.5 mg, 285 μmol, 3.60 equiv). After 10 min of vigorous stirring, tripropargylated synthon 14 (93.0 mg, 285 μmol, 3.60 equiv) was

• ≡CH); HRMS (+TOF-HRMS, m/z): [M + H]+ calculated for C51H57N3O15, 952.3862; found, 952.3843 (Δ = −2.10 ppm); [M + Na]+: calculated for 974.3682; found, 974.3662 (Δ = −2.05 ppm). Synthesis of bromoacylated dendron 18: To a solution of tripropargylated synthon 14 (140.0 mg, 393.0 μmol, 1.00 equiv) and