Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• operationally simple fluorination strategy suitable for bioactive structural motifs. Manganese-catalyzed late-stage C–H azidation In organic synthesis, organic azides are of considerable significance in the fields of medicinal chemistry, chemical biology, and nanotechnology as they can participate in elegant

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• industry. The current review aims to cover a wide literature survey of numerous synthetic strategies. Recent reports (2017–2021) in the field of 1,4,5-trisubstituted 1,2,3-triazoles are emphasized in this current review. Keywords: azides; Click reaction; [3 + 2]‐cycloaddition; fully functionalized 1,2,3

• applications of these five-membered N-heterocycles are the result of both their easy synthetic procedures and ring functionalization [9][31][32]. Typically, 1,2,3-triazole derivatives are prepared via a 1,3-dipolar cycloaddition reaction between azides and alkynes [33]. It is worth noting that the metal

• 1,2,3-triazoles through multicomponent reactions and the relevant mechanistic aspects have been surveyed by Chen, Ren, et al. [27]. The 1,3-dipolar cycloaddition reaction between azides and alkynes is the most efficient pathway for the preparation of disubstituted 1,2,3-triazole derivatives. The copper

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• azides and alkynes [14][15]. However, the formation of the nitrogenated azoles by the classical Huisgen methodology is slow due to its high activation energies and also lack of regiochemical control, in general, leading to a mixture of 1,4- and 1,5-regioisomers of 1,2,3-triazoles. Later, Sharpless and

• alternative approach for the synthesis of such triazole moiety 3a is the [3 + 2] cycloaddition between alkynes and the corresponding azides. However, the major disadvantage of such a strategy is the use of 3-azidoenone which is difficult to handle owing to its explosive nature. Therefore, our method provides

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• modifications were introduced into the DNA backbone using the Staudinger reaction between the 3’,5’-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• , conveniently prepared by [3 + 2] cycloadditions of terminal alkynes with sulfonyl azides, have been used as the precursors to N-sulfonylindoles by transition-metal-catalyzed transannulation reactions. In the presence of Rh(II) or Ni(0) catalysts the triazole ring-opening takes place and intermediate highly

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

• of vinyl azides, or by other strategies involving oximes, imines and oxazoles [24]. One appealing strategy for the preparation of 2H-azirines involves the use of readily available vinyl azides [25][26][27][28][29][30]. However, the batch cyclization of vinyl azides into the corresponding 2H-azirines

• could generate some risks, due to the explosive nature of organic azides, and possible overpressure issues caused by nitrogen generation at high temperatures. Consequently, scalability and control of this processes represents a real challenge. The exploitation of microfluidic technologies has therefore

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4-carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5

• -arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. Keywords: amidines; Dimroth rearrangement; isoxazoles; sulfonyl thiazoles; thioamides; 1,2,3-triazoles; Introduction The biological activity

• commonly used methods to prepare these compounds include the Cu-catalyzed multicomponent reaction of alkynes, sulfonyl azides and amines [23][24][25][26][27][28][29][30][31], the reaction of thioacetamide derivatives and cyclic thioamides with sulfonyl azides [22][32][33], the chlorophosphite-mediated

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• -forming repeat unit from the “insulin-linked polymorphic region” (ILPR) [50], that was also shown to bind quadruplex ligands [51]. Results Synthesis As the Cu-catalyzed click reaction between azides and alkynes is a well-established method for the variable functionalization of G4-DNA ligands [52], the

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• . Keywords: alkynes; azides; host–guest; macrocycles; molecular knots; Introduction Macrocycles have played a central role in the development of molecular recognition, self-assembled molecular devices, and molecular topology [1][2][3][4][5][6]. For example, early work by Pedersen on crown ethers [1], Lehn

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• , Università del Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy Dipartimento di Chimica, Università di Bari “Aldo Moro”, Via E. Orabona 4, I-70125 Bari, Italy 10.3762/bjoc.16.158 Abstract We report that phenacyl azides are key compounds for a regiodivergent synthesis of valuable, functionalized

• °C) in the presence or absence of bases (Et3N). Keywords: deep eutectic solvents; imidazoles; phenacyl azides; phenacyl halides; pyrimidines; Introduction In a world with dwindling petroleum resources, the setting up of more and more sustainable routes for the preparation of heterocyclic compounds

• (g) heterogeneous “click” cycloaddition reactions [15] using DESs as environmentally responsible and non-innocent reaction media. Telescoped, one-pot transformations of phenacyl halides to symmetrical 2,5-disubstituted pyrazines (A), through phenacyl azides as intermediates, were also found to take

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• triazole 45 in 83% yield. Photophysical properties Finally, we examined the photophysical properties of both the azides and the triazoles. UV–vis absorption measurements of para-bromobenzaldehyde 3 and ortho-bromobenzaldehyde 4 as well as the corresponding triazoles 33–40 were conducted in chloroform

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• for the synthesis of 3-(bromomethyl)coumarins. Literature-reported cycloaddition reactions of MBH acetates involving azides and alkynes [24][25][26][27][28]. Synthetic methodologies for triazolations of MBH adducts. a) Literature-reported indirect triazolation of MBH adducts [32][33]. b) This work

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• sulfonyl radical, prone to start a tandem sulfonylation/annulation of vinyl azides [84]. Recently, the phenanthridine core was assembled through a radical cascade triggered by the trifluoromethylthiolation of N-(o-cyanobiaryl)acrylamides. The process occurred under visible-light irradiation (6 W blue LED

• heteroarylalkynes. Synthesis of noravicine (14.2a) and nornitidine (14.2b) alkaloids. Gram-scale synthesis of the alkaloid trisphaeridine (15.3). Synthesis of phenanthridines starting from vinyl azides. Synthesis of pyrido[4,3,2-gh]phenanthridines 17.5a–d through the radical trifluoromethylthiolation of N-(o

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• the anticipated glycopeptides, we started from the respective fully acetylated β-ᴅ-glycosyl azides 1a–f in the gluco, galacto, manno, cello, lacto, and malto series (Scheme 1). These glycosyl azides were prepared from the corresponding halogenoses by the treatment with 1.2 equivalents of sodium azide

• NaN3 in DMF) [23], the azide 1c could be obtained in 33% yield (compared to the reported 13%). Attempts to prepare the corresponding α-ᴅ-mannosyl azide under various previously described conditions [27][28] failed in our hands though. Next, the glycosyl azides 1a–f were converted into the corresponding

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• protecting groups [12]. Later, ruthenium complexes-catalyzed alkyne–azide cycloadditions (RuAACs) regioselectively produced the opposite form of the disubstituted triazoles. Thus, a wide range of azides was reacted with diverse nonactivated terminal alkyne substrates using ruthenium complexes to generate

• two-component or three-component “click” reactions. In the two-component reaction, acetylene compounds and organic azides were stirred in dimethylformamide or in a mixture of t-BuOH/H2O, 3:1, v/v as the solvent using diethylisopropylamine and SiO2–Cu. In the three-component example, acetylene species

• nitride-supported copper nanoparticles was disclosed by Islam and co-workers (Scheme 18) [79][80]. The nanocatalyst 87 was successfully used as a high-performance photoreactor promoting “click” reactions of alkynes with organic azides under light irradiation in the absence of basic condition. In the first

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• area, reporting on the synthesis of the first heteroleptic bis-NHC and mixed NHC/phosphine copper(I) complexes [20][21][22]. Interestingly, these new copper-based complexes have shown excellent activity in the [3 + 2] cycloaddition reaction of azides/sulfonyl azides and alkynes (Scheme 1, right) [22

• 6 was also shown to be active in water and in 1,4-dioxane. Based on these results, a reaction scope was conducted under solvent-free conditions, in air, using 1 mol % of [Cu(Triaz)2]BF4 6 (Scheme 3). Functionalised azides were reacted with phenylacetylene and diisopropylamine resulting in good to

• shown applicable to phosphoryl azides; and reaction of phenylacetylene with diisopropylamine and diphenylphosphoryl azide leads to the formation of the corresponding phosphorylamidine product [34] in good yield (Scheme 7), using 2 mol % of catalyst under mild conditions (solvent-free, room temperature

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• -phosphine ligands of type 136 were prepared by reacting phosphoacetylene 134 with different alkyl azides to generate the borane-protected ligand 135. The protection is necessary because it prevents the formation of iminophosphorane during the click reaction. The click-phosphine ligands 136 can be liberated

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• "click" chemistry [16][17][18] of azides and alkynes catalyzed by Cu(I) salts, the CuAAC reaction. Self-assembling properties were not observed for any of the prepared monotriazoles, namely the 4-substituted 1-glucopyranosyltriazoles 1a–g and 2a–g (Scheme 1) [15]. However, most ditriazoles 7a–g and 8a–g

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• zinc from the coordination sphere of the porphyrin macrocycle and gave the free base maleimide porphyrin 6 in a quantitative yield. A successful formation of the fluorinated porphyrin azides 3a and 3b allowed their utility as intermediates in the further porphyrin core functionalisation especially with

• 1,2,3-triazole heterocycles via the copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC) between alkynes and azides, developed independently by Sharpless [41] and Meldal [42]. In addition to the applications of triazoles as pharmacophores in the potential biologically active molecules, these

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• ][13]. The approach required five isolations only. Unlike Magano [1], the authors could not avoid the use of the potentially explosive azide chemistry. The azide intermediate was not isolated to address the safety concerns posed by azides. Positively, their approach was characterised by low catalyst

• . NaN3 proved to be the best azidating agent (Figure 18). It is evident that the application of ionic bonded azides (NaN3 and TBAA) gave almost similar conversion, 100% and 93%, respectively. Whilst the use of covalently bonded azides (DPPA and TMSA) resulted in lower conversions, 84% and 81

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• prospect of the tetrazole hybridization strategy in drug discovery. Among the most versatile methods for obtaining tetrazoles are the Ugi-azide four-component reaction (Ugi-azide-4CR) [14][15][16] and the 1,3-dipolar cycloaddition of azides with (acyl)cyanides [17][18]. The Ugi-azide-4CR enables the

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• [6][7], anhydrides [8], esters [9], and acyl azides [10] with amines by employing coupling reagents [11]. Alternative protocols include the Staudinger–Vilarrasa reaction [12], Schmidt reaction [13][14], Beckmann rearrangement [15], aminocarbonylation of aryl halides [16], Staudinger ligation [17

• -workers also demonstrated a transition metal-free aerobic oxidative cleavage of C–C bonds of phenacyl azides employed in the construction of amides utilizing benzylamines [41]. Herein we wish to report a metal-free C(CO)–C(α) bond cleavage of pyridinium salts of phenacyl bromides for the facile synthesis