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

• tandem reaction proceeds via formation of a Schiff-base 39 and subsequently 1,3-dipolar cycloaddition to produce the intermediate 42. Then, the intermediate 42 affords the final product 43 via an oxidative aromatization process in the presence of air or iodine (Scheme 15). To propose a precise mechanism

• , a cyclization reaction was carried out without molecular iodine in an inert atmosphere. No final product was observed, and only 42 was achieved in good yield. However, 42 was effectively transformed into the corresponding product with excellent yield in the presence of molecular iodine (Scheme 15

• that the reaction requires a strict control of the temperature in the different steps, while the nature and position of the substituents of the aryl azide do not influence the yield of the reaction. The use of aliphatic alkynes, as well as the replacement of bromine and chlorine with iodine, leads to a

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• unsymmetrical 3,3'-diindolylmethanes (DIMs) with a quaternary carbon center has been developed via iodine-catalyzed coupling of trifluoromethyl(indolyl)phenylmethanols with indoles. In contrast to previously reported methods, the new procedure is characterized by chemoselectivity, mild conditions, high yields

• via an iodine-catalyzed coupling reaction of trifluoromethyl(indolyl)phenylmethanol with indole derivatives. This method has also been extended to the synthesis of pentafluoro-ethylated and heptafluoro-propylated DIMs in excellent yields. Selected compounds were evaluated in radioligand binding

• 3a as an example, as depicted in Figure 5. We suggest that the reaction is initiated by iodine-mediated activation of the secondary alcohol in compound 1a (A), followed by elimination of HOI to generate the vinyliminium ion species B (see mesomeric structure C) [52]. This electrophilic intermediate

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• alkaloid ingenine B [20]. The iodine-catalyzed [3 + 3] cycloaddition of indolyl alcohol to enaminones [21] and the thiourea-catalyzed iso-Pictet–Spengler reaction of isotryptamine with aldehydes [22], are some noteworthy contributions to the field. A cascade or domino reaction is an interesting approach

• thin-layer chromatography (TLC) was carried out on silica gel plates (silica gel 60 F254 aluminum supported plates), and the spots were visualized with a UV lamp (254 nm and 365 nm) or using chemical staining with Brady’s reagent, KMnO4, ninhydrin, iodine, and bromocresol. Column chromatography was

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -headed nucleosides 151a–d starting from LNA uridine diol 147 which in turn was synthesized from diacetone-α-ᴅ-allose following a procedure reported in the literature [76]. LNA uridine diol 147 was reacted with iodine and ceric ammonium nitrate (CAN) in acetic acid to afford the nucleoside 148. Nucleoside

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• chemist Georges Denigès (1859–1951), who, however, published his discovery of the same reaction six months after the disclosure by Guareschi. The ability of the test to distinguish between iodine and bromine is remarkable and difficult to explain in the light of the mechanism by which the Schiff reagent

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• is similar to that of 2 (at 3.569(2) Å) (Figure 4A). Additionally, the edge-on interactions show the same tilted motif seen in compound 1. However, this is combined with a new halogen directed close packing between the iodine atom and the edge of the porphyrin ring in a repeating step-wise pattern

• this case, is the marked decrease in the CaCmCa of 2° seen in compound 3. Generally, all atom displacements (Δ24, ΔN, ΔCa, ΔCb, and ΔCm) [20] show a significant increase along with the pyrrole tilt angle which are moderately increasing when substituting a bromine atom for an iodine atom. This, however

• equal and it is only in the IP modes that they differ with an increase in the B2g and a corresponding decrease in the A1g distortion modes (Supporting Information File 1, Figure S17). The final structure in this series is the iodine and hexyl combination (compound 8). In this structure, the stacking is

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -electron transfer occurs under white-light irradiation, leading to an electron-deficient fluoroalkyl radical. Thereafter, fluoroalkyl radical is captured by 87, affording radical 88 that gives rise to radical intermediate 89 by uptake of iodine. Finally, the dealkylation product 86 is given by removing

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

• functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N2 alkylation [27], organocatalytic N1 alkylation [28][29], N2-arylation using hypervalent iodine (Scheme 1c) [30], N2-alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N1

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

• TsN3 in MeCN or 0.7 M 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide in DMF) was introduced as replacement of a standard iodine/pyridine oxidation step to react with 3',5'-dinucleoside β-cyanoethyl phosphites (Scheme 1, I), forming the N-modified iminophosphorane (Scheme 1, II). ONs bearing

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• dibromodifluoromethane is a suitable source of difluorocarbene. However, the same reagent produces low yields in the reactions with electron-deficient alkenes. Dolbier et al. reported the cyclopropanation of α-methylstyrene (7) using dibromodifluoromethane and zinc dust in the presence of iodine (Scheme 3) [18]. The

• Nazarov cyclization with the strong silylating agent Me3Si+ B(OTf)4− to afford the corresponding 2-fluorocyclopentenone derivatives, e.g., compound 124 (Scheme 54) [37][90]. Radical-mediated ring-opening reaction: The photochemical iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl

• (methylene)cyclopropanes (F2MCPs) of type 139 (Scheme 61) [112]. The heating with iodine in the presence of CuI resulted in the cleavage of the proximal C2–C3 bond and the overall addition of a molecule of iodine to give products 141 in high yields. Xiao et al. described a direct synthesis of 2

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• azopyridines with molecular iodine or bromine [9]. Interestingly, the broadest mesophase temperature ranges were found for the bromine-based assemblies and not as anticipated, for the iodine system which yields a stronger halogen bond. In order to prove that the halogen bond plays a crucial role for the

• induction of liquid crystallinity in our assemblies, we synthesised a series of azo compounds with decreasing fluorination degree at the halogen bond donating iodobenzene [12]. Reducing the number of the fluorine atoms at the halogen bond donating moiety lowers the polarisation of the iodine atom and thus

• . This is in accordance with our previous results on pyridine-based assemblies and supports the assumption that a reduction of the fluorination degree at the iodobenzene yields a weaker polarisation of the iodine and thus a weaker halogen bond [12]. To investigate this effect experimentally, a series of

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• access to dienylboronate (rac)-19a in 43% yield. A competitive Suzuki coupling was also observed with compound (rac)-19b being isolated in 35% yield [32][33][34][35]. Dienylboronate (rac)-19a was then transformed into dienyl iodide (rac)-20 by iodine monochloride addition and methoxide-mediated

• reduction as reported previously [56]. Similarly, the treatment of (+)-83 with in situ-generated Schwartz’s reagent from zirconocene dichloride and DIBAL-H followed by iodine to produce an inseparable 6:1 mixture of (Z,E)-iododiene 85a and its 6-iodo-isomer 85b in 82% yield (Scheme 8). The vinyl iodide (Z,Z

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• very sensitive to the amount of ICl used. In the case of 2a, the use of a 1.5-fold excess of ICl led to a hardly separable mixture of compound 7a and diiodo derivative 8a (Table 3, entry 1, for the NMR spectrum of the mixture see Supporting Information File 1, Figure S13). Iodine chloride, taken in an

• equimolar amount, made it possible to obtain the required product 7a in 65% yield and to remove minor impurities of diiodo derivative 8a by chromatography (Table 3, entry 2). For the selective synthesis of 7b, iodine chloride was taken in a small deficit (Table 3, entries 3 and 4). Compound 8b was

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• iodine by treatment with zinc, followed by the reaction with iodine monochloride. The iodide 2b reacted quite rapidly with the nitrone but the expected fluoroalkylation product was not observed. Instead, the tetrafluorinated piperidine 3a was obtained in a moderate yield (Table 1, entry 2). Apparently

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• acid, as previously reported [45]. In the next step, the electrophilic addition of iodine monochloride to the double bond of the enesulfonamide 10, followed by a nucleophilic attack of methanol on the formed iodonium ion afforded the α-methoxy-β-iodopiperidine 11 as a single stereoisomer (91% yield

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -workers in 2014 [49] (Scheme 9A). The synthesis began with the conversion of ketone 112 into alcohol 113 in four steps, which involved a hypervalent iodine-mediated ring expansion [60]. A two-step synthesis from 113 gave epoxide 114. Epoxide 114 was converted to the corresponding β-ketoester and

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• halide to iodine, taking into account that direct iodination of purines has been claimed being troublesome [26], although not impossible [27]. For C8-iodination of adenosine, first the hydroxy groups at the sugar moiety were protected with tert-butyldimethylsilyl (TBDMS) groups. The silylated nucleoside

• 2 was dissolved in THF and lithium diisopropylamide (LDA) was added, followed by iodine in THF. The reaction temperature was kept strictly between −70 and −80 °C to make sure that iodination proceeds without further side reactions (Scheme 1) [28]. Despite the fact that the exocyclic amino group was

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• spectrum at 528 nm (Figure S1 in Supporting Information File 1). Further structural information was obtained by releasing the ligand molecules from the surface of NPrac-1 with iodine, adding a known amount of 2,4,6-trimethoxy-1,3,5-triazine to the solution as an internal standard, and recording an 1H NMR

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• -workers have recently described a method for the one-step, diastereoselective 1,2-difluorination of alkenes, mediated by a hypervalent iodine catalyst [24]. The substrate scope of the Jacobsen method has certain constraints but their original report did include some examples of α,β-unsaturated amides, and

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• Oxone™ (Wegner et al. [19][20][21], Scheme 1). Isolation of 3 was achieved, however, a one pot approach including a subsequent Baeyer–Mills reaction to yield 10 is preferred. 1-Iodo-3-nitrosobenzene (6) cannot be prepared by oxidation of the corresponding aniline because hypervalent iodine is formed [22

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• the larger iodine cation to a greater extent. With this in mind, we also tried the chlorofluorination of compound 19. Again, two chlorofluorinated products were formed, but only (rac)-20c could be isolated in a pure form (Scheme 12). Chlorofluorination is usually inferior in terms of the yield when

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• ketyl radical anion 166•−. The latter intermediate 166•− can then abstract an iodine atom from another molecule of 163 to propagate the chain reaction and generate alkyl iodide 167, which collapses to give the desired enantioenriched alkylation products 168 in moderate yields and excellent

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• yield. Next, compound 202 was treated with KI/NaNO2 under Sandmeyer reaction conditions to afford the triiodo compound 203 which on subsequent reaction with mCPBA and triflic acid (TfOH) provided the iodine-doped sumanene 204 in 68% yield. Finally, compound 204 was converted to the required

• tritellurasumanene 205 through the reaction with Te powder in the presence of tetrabutylammonium bromide (TBAB) and 2-picoline in DMSO as shown in Scheme 49. Interestingly, as can be pointed out from Scheme 49, pristine trithiasumanene 151 and triselenasumanene 206 were also obtained from the common iodine-doped

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• thiocyanate 2 in the presence of several oxidants and metal salts (Table 1). The initial attempts employing iodine, CAN and ZnCl2 upon refluxing in acetonitrile for 6 hours did not yield any product (Table 1, entries 1, 2 and 4). When potassium persulfate (K2S2O8) is employed, highly substituted oxazole 3i

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• establish high-yielding and selective oxidative coupling reactions, has afforded new and greener synthetic protocols for biaryls [5][6][7]. Several oxidants, such as the salts of Ag(I&II) [8], Ti(III&IV) [9], Mn(III) [10], Ce(IV) [11], Sn(IV) [12] and Fe(III) [13], as well as the hypervalent iodine reagents

• aqueous conditions to prevent complexation of the reagent and the starting material. Of the Lewis acids used, stannic chloride proved to be the most effective oxidant for dimerization (Table 1). However, the hypervalent iodine reagents PIFA and PIDA gave better results overall, affording dimer 18 in 63