Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• Guthrie in the 1860s as an attraction between ammonia and molecular iodine [19]. The 20th century saw halogen bonding extended to organohalides such as diiodoacetylene [25][26], and also saw the first X-ray crystallographic evidence of a ‘halogen molecular bridge’ between molecular bromine and 1,4-dioxane

• weakening in the host/donor R–X bond, and an accompanied decrease in the HOMO–LUMO gap which may be experimentally observed as a red-shift in the vibrational frequency [46][47][64][65]. 1.2 Halogen bonding in monovalent iodine The σ-holes expressed by both molecular iodine and other organoiodine compounds

• halogen bond lengths and their interaction energies [66][67][68][69][70][71]. Comparing the VS,max of select iodine-containing molecules shows that the electrostatic potential for molecular iodine (I-1) was 0.049 e, significantly greater than that of iodobenzene (I-2, 0.027 e) [70][72], though identical

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• –98% yields by reacting various amines 60 and 2,5-DMTHF 2 under solvent-free conditions in the presence of 5 mol % molecular iodine as catalyst (Scheme 29a). These synthesized products were tested against various cancer cells in vitro. In the proposed mechanism, deprotection of the methoxy group of

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• and to determine the possible active intermediates involved, several control experiments were carried out. As shown in Scheme 4, when molecular iodine was employed as oxidant, the desired product 3a was obtained in a 67% yield under otherwise identical conditions (Scheme 4a), but without passing

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• Information File 1, Table S1, entries 4 and 5). When molecular iodine or NIS were used as oxidants, product 5a was obtained in 83% and 80% yield, respectively (Supporting Information File 1, Table S1, entries 6 and 7). However, the yield of the desired product 5a slightly decreased to 92% with lowering of the

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• expected products [76]. Sun and co-workers modified the method proposed by Singh. In 2011, they reported a method that employed molecular iodine as the catalyst, under microwave radiation as heat source, and obtained tetrahydrobenzo[a]xanthene-11-one and diazabenzo[a]anthracene-9,11-dione derivatives in

• good to excellent yields (70–94%) [77]. Then, in 2012, Sun and co-workers reported another method employing molecular iodine as catalyst under reflux with acetic acid instead of microwave radiation and also obtained good yields (66–89%) [78]. Because the three methodologies provided good yields, the

• -Proline-catalyzed [4 + 2] cycloaddition reaction of naphthoquinones and α,β-unsaturated aldehydes. Iridium-catalyzed [2 + 2 + 2] cycloaddition of a 1,2-bis(propiolyl)benzene derivative with alkynes. Synthesis of several anthraquinone derivatives by using InCl3 and molecular iodine. Indium-catalyzed

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

• , 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

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

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• innocuous, water-soluble byproducts, such as iodide and sulfate salts, and uses inexpensive molecular iodine to facilitate the hydration. Moreover, unlike other metal-free alkyne hydration procedures, heat and strong acids are not required [17][18][19][20]. The reaction proceeds under mild conditions at

• were much slower as compared to what has been reported for the larger-scale processes. Initial attempts to observe the intermediate 9 involved the treatment of 8 with two equivalents of molecular iodine in deuterated acetonitrile (Figure 1a and Figure 1b). Significant changes in the 1H NMR spectrum of

• chloride anion produced using ICl is less nucleophilic than iodide released from molecular iodine. As such, it was thought that the deiodination of intermediate 9 would proceed at a slower rate with Cl− and hence, the intermediate would be longer lasting. This proved true: after five hours in the presence

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

• ) [119]. In this reaction, iodine promoted the formation of iodo-intermediate 98 with a carbonyl compound that underwent nucleophilic substitution with 2-AP 3. CuO played multiple roles in this reaction. Firstly it acts as an oxidizing agent to convert molecular iodine to the reactive iodonium ion (I

• +) species, secondly as a weak base to neutralize HI and next to reoxidize the iodide ion (I−) to molecular iodine (I2, Scheme 33). The reaction has enjoyed a broad substrate scope including arylmethyl, heteroaryl, α,β-unsaturated methyl ketones, β-ketone esters and 2-APs-substituted with EW and EDGs. The

• tandem synthesis of 3-iodoimidazo[1,2-a]pyridines (Scheme 35) [120]. The synthesis was similar to that reported by Kumar and co-workers with the difference of a heterogeneous catalytic system and iodination of the product [121]. Molecular iodine was used as an iodinating agent in the reaction. In this

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• are trapped by molecular iodine which is produced under catalytic conditions via the reduction of iodate. While iodine is produced under experimental conditions via the reduction of iodate, it is not entirely clear what the origin of all the electrons for this process is given that the benzylic

• oxidation is only a net 2 electron process. Previous research shows that the rate of radical trapping by molecular iodine nears diffusion control, similar to that of diatomic oxygen [68][69][70]. This process of radical trapping was probed through the pyrolysis of tert-butyl 2-(naphthalen-1-yl

• )ethaneperoxoate (10), a benzylic radical precursor [71], in the presence of molecular iodine. Heating of this acyl perester at 100 °C for 1 hour in the presence of molecular iodine yielded acetate ester 7a in 69% yield and the benzylic iodide 11 in 29% yield (Supporting Information File 1, Figures S3 and S4

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• screening of the oxidants revealed, that the use of molecular iodine gave the desired product with 27% yield (Table 1, entry 4), while employment of NaOCl, NaIO4, MnO2, H2O2, or CuI/TBHP was not effective and led to the formation of complex mixtures (Table 1, entries 5–9), and use of CAN did not promote the

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• -(phenylselanyl)-1H-pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis. Keywords: diaryl diselenide; diazo compound; 1H-pyrazole; molecular iodine; multicomponent reaction; Introduction Selenium-containing compounds are of great

• (Scheme 2). The reaction is catalysed by molecular iodine in MeCN as solvent. Results and Discussion Initially, to optimize the reaction conditions experiments were performed using benzoylacetonitrile (1a), phenylhydrazine (2a) and diphenyl diselenide (3a) as standard substrates to define the best

• diphenyl diselenide (3a, 0.5 mmol) were solubilized in MeCN (3 mL) and molecular iodine (50 mol %) was added. The mixture was stirred at reflux temperature and after 48 h under these conditions, the expected product 4a was obtained in 71% yield (Table 1, entry 1). With these result, we attempted to

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• formation of 4d represents the first Markovnikov-selective alkene hydrobromination by an HAT pathway. Attempts to extend this reaction to hydroiodination using related reagents, p-toluenesulfonyl iodide, N-iodosuccinimide, or molecular iodine failed to provide the expected product (see Supporting

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

• molecular iodine. In the optimized reaction conditions (Table 1, entry 2) iodo-oxyimidation of various vinylarenes were performed in order to study the scope of the developed method (Figure 1). The iodo-oxyimidation successfully proceeded using styrenes having both electron-withdrawing (Cl, F, Br

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• substrate for the synthesis of natural product (+)-biscarvacrol (157). Koag and Lee [140] reported the synthesis of a spiroketal by radical cyclization of a steroidal alkylamine in presence of PIDA (15) as oxidant and molecular iodine in dichloromethane at low temperature. It is an example of hypoiodite

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• stereoselective trans iodo-benzoylation of glycals using a combination of IBX and molecular iodine, that is considered as a source of I+ formed from the in situ generated hypoiodite species [30]. The controlled oxidation of various N-(alkyl)- and N-(aryl)pyrroles with Dess–Martin periodinane also leads to

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• more user-friendly protocols that rely on Oxone® [20], DIB [24], or PIFA [25] since the iodide source is an iodide salt and not molecular iodine. Chlorination In the case of chlorination, we have yet to observe adducts arising from the vicinal difunctionalization of the double bond and, in accordance

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

• hypervalent iodine reagent were reported, both of which include the formation of benzyl radicals during the key initial reaction step. Togo and co-workers developed a reaction system consisting of stoichiometric amounts of PIDA with catalytic amounts of molecular iodine and p-toluenesulfonamide for the

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• substrate, have recently emerged, these methods have limited substrate scope [17][18][19][20]. A seminal work on decarboxylative functionalization in which a combination of PhI(OAc)2 and molecular iodine (I2) are used was reported by Suárez et al. [21]. The method features mild reaction conditions, simple

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -phenylcoumarin (3Aa), 3-iodo-4-phenylcoumarin (3Aa’), and 3-bromo-4-phenylcoumarin (3Aa) in 28, 49 and 46% yields, respectively (Table 2, entries 3–5). The treatment of phenyl ester 2Aa with molecular iodine (2.0 equiv)/K2CO3 (2.0 equiv) did not generate 3-iodo-4-phenylcoumarin (3Aa’) at all (Table 2, entry 6

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• ). However, NCS-cericammonium nitrate (CAN) successfully yielded mono-chlorinated products [88]. Consecutively, the same group reported metal-free oxidative iodination of electron rich aromatic rings with molecular iodine and oxone (Scheme 25) [98]. This method proved to be highly chemoselective and no

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• ], although the direct β-iodination of enol ethers using a suitable electrophilic iodine reagent is relatively underdeveloped. For the iodination of 4-alkoxy-3,6-dihydro-1,2-oxazines 3, we selected molecular iodine as the most simple iodination reagent in the presence of a base [28][29][30]. A clean reaction

• the enol ether unit of 3,6-dihydro-2H-1,2-oxazines 3 can efficiently be converted into the corresponding 5-iodo-substituted compounds 4 under mild reaction conditions using molecular iodine in the presence of pyridine as base. The obtained alkenyl iodides 4 are ideal candidates for further

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• directionality that might make these interactions of a great value to the field of organocatalysis [71][72][73]. Molecular iodine has been used for many decades as a mild catalyst or promoter of various organic transformations such as conjugate addition, imine formation or aldolate dehydration reactions [74][75

• ][76][77][78][79]. Interestingly, such reaction mechanisms are not well understood, and the formation of trace quantities of hydroiodic acid rather than the direct substrate activation by molecular iodine has been frequently invoked to rationalize the outcome of these studies. Recently, Breugst and co

• -workers have re-evaluated the molecular iodine-catalyzed conjugate addition to α,β-unsaturated carbonyls or nitrostyrenes (Scheme 14) [80]. Based on their computational studies, they proposed that iodine activates the enone moiety by forming a halogen bond with the carbonyl and thus forming a more

TBHP-mediated highly efficient dehydrogenative cross-oxidative coupling of methylarenes with acetanilides

• Cui Chen,
• Weibing Liu and
• Peng Zhou

Beilstein J. Org. Chem. 2016, 12, 2250–2255, doi:10.3762/bjoc.12.217

• reaction does not occur in the absence of molecular iodine (Table 1, entry 14), which indicates that molecular iodine is requisite for this conversion. We were pleased to find that an excellent product yield of 86% was obtained (Table 1, entry 15) when increasing the loading of TBHP to 3.0 equivalents

• by the formation of 3aa. Initially, toluene (1a) reacted with molecular iodine and TBHP to produce the 1-(iodomethyl)benzene (4) and benzaldehyde (5) [21][22]. Intermediate 6 was generated from the coupling of 2a with intermediate 4 [22], by eliminating a molecule of HI. According to the results of

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• methylketones 75 in the presence of molecular iodine, respectively. The tandem transformation of a carbonyl acetalization and a iodination in sustainable ethylene glycol under mild heating provided a practical approach in the synthesis of useful protected α-haloketones (Scheme 25). Recently, Kakiuchi and co