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

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

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• suppressed catalysis. The prerequisite for this substructure was established by molecular editing and was complemented with a physical organic investigation of possible determinants. Keywords: α-fluoroketone; alkyne; fluorination; hypervalent iodine; organocatalysis; Introduction The venerable role of

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• Sandmeyer-type reaction (Scheme 7, reaction a) [49]. The reaction was efficient, although heteroaryl diazonium salts were reluctant in this reaction. To overcome these limitations, hypervalent iodinated species were used as substrates. The copper-mediated reaction with λ3-iodanes demonstrated a large

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• valuable enol phosphonates in very good yields. Keywords: alkenylation; copper; C(sp2)–O bond formation; hypervalent iodine; phosphonates; Introduction Organophosphorus compounds represent an important class of products with a wide range of applications in biology, agriculture and synthetic organic

• (alkenyl)iodonium salts, which are air- and moisture-stable, nontoxic and easy to prepare compounds, have become efficient reagents for mild and selective arylation and alkenylation reactions in organic synthesis [16][17][18]. In particular, the use of these hypervalent iodine reagents in copper catalysis

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• high reaction temperature, extended reaction time, involvement of transition metal catalysts, and low yield. In these regards, the development of alternative approaches that can realize an efficient synthesis of chromones under mild conditions is desirable. In recent decades, hypervalent iodine

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• et al. described the electrophilic chlorination of arenes and heterocycles by 1-chloro-1,2-benziodoxol-3-one (12) [18][19]. The hypervalent iodine(III) reagent 12 is reported to be a mild and effective reagent for the chlorination of nitrogen containing heterocycles which is easy to prepare and is

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• stability with reactivity in a model oxygenation. Keywords: differential scanning calorimetry; hypervalent iodine; N-heterocycle; stability; thermogravimetry; Introduction Hypervalent iodine compounds, in particular aryl-λ3-iodanes, have found wide spread applications as oxidants and electrophilic group

• transfer reagents in organic synthesis [1][2][3][4][5][6][7][8][9][10][11]. A 3-center 4-electron bond connects the central iodine atom, providing two electrons, with two carbon- or heteroatom ligands L1 and L2, providing one electron each (Figure 1). These ligands can be arranged along the hypervalent

• electrophilic hypervalent iodine atom in its ground state or directly influences its reactivity by stabilizing reactive intermediates or transition states. In recent years, a plethora of cyclic and pseudocyclic iodanes have been developed with covalently attached stabilizing ligands L2 and applied in a variety

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• fluoride source and PhI(OPiv)2 as a hypervalent iodine oxidant (Scheme 8). Very recently, they [44] optimized this transformation and achieved the benzylic C–H radiofluorination with no-carrier-added Ag[18F]F. This method was applied to the radiolabeling of diversely substituted 8-methylquinoline

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• ][22][23][24]. Huber and co-workers demonstrated the activation of a carbonyl group by halogen bonding, and successfully applied this concept to catalysts for Michael addition reactions [25] and also employed neutral [26], and hypervalent iodolium derivatives as activators in a halide abstraction

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

• , hypervalent iodine reagents, etc. The synthetic methods towards diverse [1,2,4]triazolo[3,4-a]pyridines have been reviewed in detail [12][13]. It should be noted that the use of acetylene species to create this heterocycle (including triazole ring) is presented only by few examples. There has been reported

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

• hypervalent iodine species as a terminal oxidant. Combinations of ammonium iodate and catalytic N-hydroxyphthalimide (NHPI) were shown to be effective in the selective oxidation of n-butylbenzene directly to 1-phenylbutyl acetate in high yield (86%). This method shows moderate substrate tolerance in the

• hypervalent iodine oxidants to mediate benzylic C–H oxidation is one area experiencing a surge of interest [22][23][24][25][26][27][28][29][30][31][32][33]. Nonmetal-based benzylic oxidations have also been mediated by species including, but not limited to, electron deficient quinones, photoexcited organic

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• using several arylamines and hypervalent iodine(V) reagents by direct mixing is unrealistic because of the high exothermic reaction or explosion. Herein we demonstrate, when anilines were substituted with an amide group at the ortho-position, successful chemical reactions could be performed due to

• ; contact explosive; IBX; mechanochemical synthesis; quinazolin-4(3H)-one; Introduction An iodine and ammonia mixture is a well-known contact explosive due to formation of NI3 [1]. Similarly, hypervalent iodines as oxidizing compounds [2] react violently with amines under solvent-free conditions [3

• may take place between hypervalent iodine reagents and electron-rich amines. For this reason, synthetic methods based on hypervalent iodine reagents and primary amines under solvent-free conditions or constrained media are limited [8]. Recently, we have described a method for the successful reaction

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by ¹⁷O NMR spectroscopy

• Nico Santschi,
• Cody Ross Pitts,
• Benson J. Jelier and
• René Verel

Beilstein J. Org. Chem. 2018, 14, 2289–2294, doi:10.3762/bjoc.14.203

• for the design of electrophilic transfer reagents. A particularly intriguing aspect is the fundamental II–IIII tautomerism about the hypervalent bond, which has led in certain cases to a surprising re-evaluation of the classic hypervalent structure. Thus, through a combination of 17O NMR spectroscopy

• structural elucidation technique to predict the constitution of an electrophilic iodine-based cyano-transfer reagent as an NC–I–O motif and study the acid-mediated activation of Togni's trifluoromethylation reagent. Keywords: electrophilic; hypervalent iodine; 17O NMR spectroscopy; trifluoromethylation

• ; trifluoromethylthiolation; Introduction The remarkable stability and reactivity of Togni's hypervalent iodine-based trifluoromethylation reagents (e.g., 4a) [1] have inspired the development of analogous compounds, including a well-known SCF3-transfer reagent 5 in 2013 by Shen and co-workers [2][3]. In the presence of

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

• , Ostrovitianov str., 1, 117997 Moscow, Russian Federation National Research Center “Kurchatov Institute”, Akademika Kurchatova pl., 1, 123182 Moscow, Russian Federation 10.3762/bjoc.14.188 Abstract The iodo-oxyimidation of styrenes with the N-hydroxyimide/I2/hypervalent iodine oxidant system was proposed. Among

• the examined hypervalent iodine oxidants (PIDA, PIFA, IBX, DMP) PhI(OAc)2 proved to be the most effective; yields of iodo-oxyimides are 34–91%. A plausible reaction pathway includes the addition of an imide-N-oxyl radical to the double C=C bond and trapping of the resultant benzylic radical by iodine

• . It was shown that the iodine atom in the prepared iodo-oxyimides can be substituted by various nucleophiles. Keywords: free radicals; hypervalent iodine; imide-N-oxyl radicals; iodination; N-hydroxyimides; oxidative functionalization; Introduction The presented work opens a new chapter in the

Preparation and X-ray structure of 2-iodoxybenzenesulfonic acid (IBS) – a powerful hypervalent iodine(V) oxidant

• Irina A. Mironova,
• Pavel S. Postnikov,
• Rosa Y. Yusubova,
• Akira Yoshimura,
• Thomas Wirth,
• Viktor V. Zhdankin,
• Victor N. Nemykin and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 1854–1858, doi:10.3762/bjoc.14.159

• ) heterocycle (2-iodosylbenzenesulfonic acid), while the oxidation of sodium 2-iodobenzenesulfonate in neutral aqueous solution gives the iodine(V) products. Keywords: hypervalent iodine; iodine; 2-iodoxybenzenesulfonic acid; oxidation; X-ray; Introduction Recently, the interest in synthetic applications of

• hypervalent iodine compounds as stoichiometric reagents or catalysts has experienced an explosive growth [1][2][3][4][5][6][7][8]. Hypervalent iodine(V) compounds represent an important class of oxidative reagents extensively employed in organic synthesis [9][10][11]. 2-Iodoxybenzoic acid (IBX) and the

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• the quinolones 6 and phenylhydrazine with a catalytic amount of AcOH in refluxing n-propyl alcohol. Subsequently, the hydrazones 7 were converted into the 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 via the oxidation with hypervalent iodine(III) reagent PhI(OAc)2 (Scheme 2) [45]. The

• -dihydro-4(1H)-quinolone 6a [46]. However, it was odd that the oxidation using the hypervalent iodine(III) reagent PhI(OAc)2 as described for phenylhydrazones 7 failed to produce the expected α-acetoxy-ethoxycarbonyl compound 12. Instead, the hydrazone 11 remained intact and was recovered. Therefore, we

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

• Xiang Li Pinhong Chen Guosheng Liu State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China 10.3762/bjoc.14.154 Abstract Hypervalent iodine(III

• hypervalent iodine(III)-catalyzed functionalization of alkenes and asymmetric reactions using a chiral iodoarene are summarized. Keywords: asymmetric catalysis; functionalization of alkenes; hypervalent iodine(III); Introduction Hypervalent iodine(III) reagents, also named as λ3-iodanes, have been widely

• occupying the equatorial positions, and the electronegative ligands are in the apical positions (Figure 1, 1 and 2) [8]. Hypervalent iodine(III) reagents are electrophile in nature, resulting from the node in a hypervalent nonbonding orbital, a 3-center-4-electron (3c-4e) bond (L–I–L), which is formed by

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

• Fateh V. Singh Priyanka B. Kole Saeesh R. Mangaonkar Samata E. Shetgaonkar Chemistry Division, School of Advanced Sciences (SAS), VIT University, Chennai Campus, Chennai-600 127, Tamil Nadu, India 10.3762/bjoc.14.152 Abstract Hypervalent iodine reagents have been developed as highly valuable

• reagents in synthetic organic chemistry during the past few decades. These reagents have been identified as key replacements of various toxic heavy metals in organic synthesis. Various synthetically and biologically important scaffolds have been developed using hypervalent iodine reagents either in

• stoichiometric or catalytic amounts. In addition, hypervalent iodine reagents have been employed for the synthesis of spirocyclic scaffolds via dearomatization processes. In this review, various approaches for the synthesis of spirocyclic scaffolds using hypervalent iodine reagents are covered including their

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -catalyzed 1,2-acetoxysulfenylation of Baylis–Hillman products at 50 °C under an oxygen atmosphere as shown in Scheme 35 [70]. The β-ketomethylene 94 substrate was generated in situ from the oxidation of Baylis–Hillman product 93 using a hypervalent iodine reagent (iodoxybenzoic acid, IBX) in an ionic liquid

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• donor of in the latter are carried out in the presence of an appropriate activator. As an activator of the glycosylation, a combination of a Lewis acid catalyst and a hypervalent iodine was developed for synthesizing 4’-thionucleosides, which could be applied for the synthesis of 4’-selenonucleosides as

• well. The extension of hypervalent iodine-mediated glycosylation allowed us to couple a nucleobase with cyclic allylsilanes and glycal derivatives to yield carbocyclic nucleosides and 2’,3’-unsaturated nucleosides, respectively. In addition, the combination of hypervalent iodine and Lewis acid could be

• used for the glycosylation of glycals and thioglycosides to produce disaccharides. In this paper, we review the use of hypervalent iodine-mediated glycosylation reactions for the synthesis of nucleosides and oligosaccharide derivatives. Keywords: glycosylation; hypervalent iodine; Lewis acid

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

• achievements reported in this area. Keywords: atom-economy; couplings; hypervalent iodine; oxidation; tandem reactions; Introduction Synthetic applications of the hypervalent iodine chemistry have grown exponentially in the last four decades as highlighted by several books and comprehensive reviews dedicated

• than its O-tautomer 88, the rearrangement step seems to be much faster. The use of the radical scavenger TEMPO had no effect on the reaction outcome suggesting that the initial hypothesis is correct. By screening additives, it was shown that the hypervalent iodine could be quickly generated in situ by

• application of modern transition-metal-catalyzed methods. Simple hypervalent iodine reagents can now be considered as valuable building blocks in the synthesis of both polyfunctionalized compounds and complex polycyclic skeletons. We believe that the application of this strategy could be a source of

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• -dimethyl-1,2-benziodoxole (1’, Figure 2), are effective and efficient hypervalent iodine reagents for trifluoromethylation reactions of a variety of substrates [22][23]. These reagents have found wide applications in the area of organofluorine chemistry, synthetic method development as well as medicinal

• [52][53][54][55] have been developed for accessing this exclusive class of heterocycles. In our previous works, we have realized the application of hypervalent iodine reagents for the construction of the 2H-azirine skeleton starting from enamines 2 via intramolecular oxidative cyclization (Scheme 1

• -obtained trifluoromethylated enamines could undergo a hypervalent iodine-mediated intramolecular azirination to give the corresponding trifluoromethylated 2H-azirines [56][57]. To test this conversion, the readily available enamine 5a was used as a model substrate. The treatment of 5a with Togni reagent 1

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• Andreas Boelke Peter Finkbeiner Boris J. Nachtsheim Institute for Organic and Analytical Chemistry, University of Bremen, 28359 Bremen, Germany 10.3762/bjoc.14.108 Abstract Hypervalent iodine compounds, in particular aryl-λ3-iodanes, have been used extensively as electrophilic group-transfer

• atom efficiency. Keywords: atom economy; benziodoxolones; homogeneous catalysis; hypervalent iodine; iodonium salts; Introduction Atom economy (AE) is an important parameter which helps to evaluate the overall efficiency of a chemical reaction or a chemical process [1][2]. It is defined as the

• -economical transformations using hypervalent iodine reagents (iodanes) as electrophilic group-transfer reagents. Iodanes, in particular iodonium salts, are well-balanced reagents in terms of stability, reactivity and synthetic and/or commercial availability and therefore it is not surprising to see these