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

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

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• -one (4S,5S)-20 after reduction of the carbon–iodine bond formed in the primary products of cyclization (via iodonium ion 22). Hydrogenolytic debenzylation preceded oxidation of the hydroxymethyl group to afford diester (4R,5S)-21 which after hydrolysis gave (2R,3S)-2 as the hydrochloride (Scheme 5

Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region

• Aude-Héloise Bonardi,
• Frédéric Dumur,
• Guillaume Noirbent,
• Jacques Lalevée and
• Didier Gigmes

Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282

• (TMS)3SiH), amines such as ethyl 4-(dimethylamino)benzoate (abbreviated EDB) or carbazole derivatives such as 9-vinylcarbazole (NVK) are presented. As oxidizing agent, it is possible to use a iodonium salt such as diphenyliodonium (Ph2I+). With these additives, three systems involving catalytic cycles

• triplet excited state through metal to ligand charge transfer (Scheme 3, reaction 1). As described in Table 2, the irradiation must be around 450 nm. Thus, as the triplet excited state is long enough and thanks to the values of oxidation potentials, a single electron transfer (SET) to the iodonium salt

• absorption and redox properties through well selected ligands [52]. This Ir-based complex reacts in the photoredox catalytical cycle with iodonium salt and (TMS)3SiH as the Ru-based complex in reactions 1, 2 and 3. Moreover, Iridium complexes can be interesting for applications in ring-opening

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

• HCl compound 4a afforded an isolable iodonium-type structure [20]. Although this activation can be conveniently followed by 19F NMR spectroscopy with 4a resonating at −40.1 ppm and the fully protonated “iodonium” congener 4c at −20 ppm [1], this technique provides no indication on how to best

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

• hypervalent iodine-mediated reactions to achieve the intermolecular oxycarbonylation [79], azidocarbonylation [80] and fluorocarbonylation [81] of alkenes. Mechanistic studies showed that PhI(OAc)2 is activated by the aid of BF3·OEt2 and then reacts with an alkene to form a three-membered iodonium ion

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

• iodonium diacetate 132 in 2,2,2-trifluoroethanol/DCM at −10 °C (Scheme 51). Additionally, the synthesized functionalized spirodienone 140 was used as precursor for the synthesis of (+)-plicamine (141). In 2002, Quideau and co-workers [131] developed the synthesis of marine sesquiterpenoid (+)-puupehenone

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• the basis of the mechanism the origin of the stereoselectivity is ascribed to the interaction of the Cu ion with the oxazoline oxygen driving the ring-closure step selectively. Keywords: catalysis; DFT calculation; iodonium salts; reaction mechanism; tandem arylation–cyclisation; Introduction

• Recently a very efficient synthetic strategy has been developed where diaryl iodonium salt 1 [1][2][3][4][5][6][7][8] and copper(I) catalyst 2 are employed together to produce in situ Ar–Cu(III) species 3 for the carbofunctionalisation of appropriate substrates 4 [9][10][11][12][13][14][15][16][17][18][19

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

• disaccharide 158 in good yield (Scheme 20). Randolph and Danishefsky reported a glycal assembly strategy to the synthesis of a branched oligosaccharide [82]. Bennett and co-workers reported that phenyl(trifluoroethyl)iodonium triflimide was a stable promoter for glycosylation reactions using thioglycoside

• selectively achieved in the absence of directing groups. After preliminary screens, they found that the reaction in the presence of phenyl(trifluoroethyl)iodonium triflimide 160 and the non-nucleophilic base 2,4,6-tri-tert-butylpyrimidine (TTBP) at 0 °C with the solvent combination of 2:1 CH2Cl2/pivalonitrile

• /acetonitrile/isobutyronitrile/pivalonitrile greatly improved both the chemical yields and stereoselectivity, as shown in Scheme 21. The results suggested that both the solvent system and iodonium salt promoter are required for selectivity. Even though glycals have a π-electron-rich enol ether unit, reports

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

• products 46 resulting from a 1,2-benzoyloxyiodination and isolated with moderate to excellent yields (Scheme 15). The reaction is believed to take place through the formation of a hypoiodous species that activates the olefin via an iodonium intermediate. Tandem catalytic couplings Diaryliodonium compounds

• , their reactivity is higher than that of the corresponding aryl halides, a property that has been widely exploited to develop efficient transition-metal-catalyzed cross coupling reactions [55]. The latter, however, allow for transferring only one of the two aromatic motifs of the iodonium reagents

• catalyzed cascade reaction to afford alkylidenefluorenes 49 (Scheme 17) [57]. In terms of mechanism, a Pd(0)/Cu(I)-catalyzed Sonogashira coupling reaction from the iodonium salt 48 delivers a 2-alkynyl-2’-iodoarene 50 that, then, cyclizes to 51 via insertion of the Pd(0) species into the iodoarene moiety

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• sequence, proceeding via arylation of phenols with diaryliodonium salts using our reported methodology [23][24][25]. In reactions with unsymmetrical iodonium salts, this type of O-arylation is known to have an ortho-effect, i.e., chemoselective transfer of the ortho-substituted aryl moiety [29][30]. The

• use of unsymmetrical iodonium salts facilitates the synthesis of the reagents and avoids waste of an expensive iodoarene, and we hence envisioned chemoselective transfer of the desired aryl moiety from an unsymmetrical salt with a suitable “dummy” aryl group. Two different approaches to reach 3 are

• a symmetric iodonium salt (R = 2-NHAc). In route B, the challenge would instead be the synthesis of iodonium salt 7, as the iodo substituent might be prone to oxidation. Furthermore, selective O-arylation in the presence of an amide moiety could be challenging, as N-arylation of amides with

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

• 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

• (Scheme 2a) [23]. Throughout this review, iodonium salts will be shown consequently in the latter structure due to clarity and due to literature habits. Typically, only one of the two aryl ligands is transferred to the substrate, yielding a monoarylated reaction product and aryl iodide as stoichiometric

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• ) reagent 9b was used successively for the synthesis of δ-lactones 45 in a highly stereoselective manner starting from 44 [43]. The formation of cyclic iodonium 46 is the vital part of this difunctionalization process. Wirth et al. were the first to introduce asymmetric dioxytosylation of styrene (47) using

• leading to the formation of valuable α-arylated ketones 84. In this reaction I(III) reagent 9b gave the best reaction outcome. Key to the success of the reaction is the formation of the cyclic iodonium ion intermediate 85 (Scheme 16, below part) [59][60]. Asymmetric α-functionalization strategy Methods

• more effective chiral iodonium salts 16 which were used for the α-arylation of β-ketoester 86 to deliver α-arylated β-ketoesters 87 with moderate enantioselectivity (Scheme 17) [63]. This was the first example of an asymmetric α-arylation of β-ketoesters using hypervalent iodine reagents. A more

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• (III) catalyst for C-5 and C-6 functionalization, respectively [13]. Hypervalent iodine reagents in general [20], and benziodoxole derivatives in particular [21], have found broad application in synthetic chemistry. Aryl iodonium salts have been used successfully in transition-metal-catalyzed

• transformations [22], but only one application of indole iodonium salts in copper catalysis by You and co-workers had been reported until 2017 [23]. In this context, indole-based benziodoxole hypervalent iodine reagents, recently introduced by Yoshikai's and our group [24][25][26][27], appeared ideal partners to

• ) resulted in lower yields. Finally, three control experiments with 1-methylindole (8, Table 1, entry 8), 3-iodo-1-methylindole (9, Table 1, entry 9) and the poorly stable (1H-indol-3-yl)(phenyl)iodonium tetrafluoroborate [23] (10, Table 1, entry 10) did not lead to the formation of 7a, highlighting the

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• mechanism could be occurring with metalloid groups such as silicon and boron. Hypervalent iodine reagents such as Zefirov’s reagent, cyclic iodonium reagents, iodosobenzene/BF3, and PhI(OAc)2/BF3 or triflate-based activators were tested. A desirable facet of the reported reaction is that iodine(I) is

• -withdrawing groups could also explain how the carbonyl of the cyclic iodonium (3) caused that specific reagent to fail (Table 1, entries 6 and 7). Several para-substituted I(III) reactants were attempted but all led to complex mixtures with the exception of the diaryliodonium triflate 2d (Table 2, entry 3

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• (TMP)iodonium tosylate salts. The aryl transfer from the iodonium moiety occurs under electronic control with the electron-rich trimethoxyphenyl group acting as a competent dummy ligand. The yields of N-aryl phthalimides are moderate to high and the coupling reaction is compatible with electron

• transfer [6][7][8][9][10] and Muñiz and co-workers have recently reported an elegant study on sterically controlled C–N coupling of 2,6-disubstituted aryl(phenyl)iodonium salts and imides [11]. We have been investigating the generality of electronically controlled aryl transfer from aryl(trimethoxyphenyl

• )iodonium salts [12][13][14] and describe here the development of a C–N coupling of a phthalimide anion with non-sterically biased aryl groups. The protocol is compatible with ortho-, meta-, and para-substitution on the aryl group and the phthalimide moiety may also provide access to anilines. Results and

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• Scheme 4. First, an activation of hypervalent iodine(III) by the Lewis acid generates the active iodine(III) species A in situ. The resulting iodine(III) then, in turn, forms the electrophilic iodonium intermediate B with the terminal alkene of the allyl ketone oxime or allyl ketone tosylhydrazone. The

• subsequent 5-exo-type cyclization by nucleophilic attack on the iodonium then leads to the isoxazoline or pyrazoline cores (C) bearing the hypervalent iodine(III) group. Following iodine activation by the Lewis acid, the iodonium ion D undergoes nucleophilic substitution with excess acetonitrile to form

One-pot synthesis of diaryliodonium salts from arenes and aryl iodides with Oxone–sulfuric acid

• Natalia Soldatova,
• Pavel Postnikov,
• Olga Kukurina,
• Viktor V. Zhdankin,
• Akira Yoshimura,
• Thomas Wirth and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 849–855, doi:10.3762/bjoc.14.70

• , Park Place, Main Building, Cardiff CF10 3AT, UK 10.3762/bjoc.14.70 Abstract A facile synthesis of diaryliodonium salts utilizing Oxone as versatile and cheap oxidant has been developed. This method shows wide applicability and can be used for the preparation of iodonium salts containing electron

• -donating or electron-withdrawing groups in good yields. In addition, this procedure can be applied to the preparation of symmetric iodonium salts directly from arenes via a one-pot iodination–oxidation sequence. Keywords: diaryliodonium salts; iodine; iodonium; oxidation; Oxone; Introduction

• acetonitrile, the iodonium salt 3a was formed in 75% yield (Table 1, entry 4). The addition of 2 equivalents of Oxone increased the yield to 92% (Table 1, entry 5). Surprisingly, a smaller amount of toluene did not affect the yield (Table 1, entry 6). In order to avoid the formation of undesired 4

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• group and localized at the benzylic position. This may allow the preferential formation of I3 from I1. If I2 was the major intermediate in the pathway leading to 3, the stereochemical purity of 3 would have decreased owing to the facile elimination of the iodonium group [54] at the benzylic position of

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• . These results led us to synthesize more compounds, previously unknown sterically demanding diaryliodonium salts having a pentafluorosulfanyl (SF5) functional group at the ortho-position, that is, unsymmetrical ortho-SF5 phenylaryl-λ3-iodonium salts. Newly synthesized mesityl(2-(pentafluoro-λ6-sulfanyl

• )phenyl)iodonium exhibited the greatest potency in vitro against U937 cells. Evaluation of the cytotoxicity of selected phenylaryl-λ3-iodonium salts against AGLCL (a normal human B cell line) was also examined. Keywords: biological activity; diaryliodonium salt; fluorine; hypervalent iodine; lymphoma

• -functionalized diaryliodonium salts. These findings led us to synthesize four more previously unknown diaryliodonium salts having a sterically demanding pentafluorosulfanyl (SF5) functional group at the ortho-position, that is, unsymmetrical ortho-SF5 phenylaryl-λ3-iodonium salts. Finally, one of the new

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• diaryiodonium salts in the literature. In 1995, Kitamura prepared phenyl[o-(trimethylsilyl)phenyl]iodonium triflate which could be used as an efficient benzyne precursor in trapping furans [10]. Surprisingly, the research groups of Stuart [11][12] and Wang [13] independently discovered in 2016 that simple

• cycloaddition reaction of 1-phenylpyrrole (1a) using phenyl(mesityl)iodonium tosylate (2a) as benzyne precursor. To our delight, with LiHMDS as the base in toluene, the Diels–Alder adduct 3aa was obtained in 23% yield at room temperature (Table 1, entry 1). However, when the reaction temperature was increased

• reaction time did not improve the yield of 3aa (Table 1, entries 18–21). With the optimal reaction conditions in hand, various aryl(mesityl)iodonium salts 2 were examined. As shown in Table 2, an extensive range of substituted aryl(mesityl)iodonium salts, bearing a wide variety of substituent groups, could

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

• ). Thus, the iodonium-based or bromonium-based electrophilic cyclization of phenyl 3-phenyl-2-propynoate (2Aa) does not proceed efficiently. Then, the bromo-radical-based cyclization of phenyl 3-phenyl-2-propynoate (2Aa) with tetrabutylammonium bromide (TBAB, 2.0 equiv)/Na2S2O8 (1.5 equiv) [31] in a

• (1a) with diaryliodonium triflates (1.0 equiv), such as di(p-methylphenyl)iodonium triflate (B), di(tert-butylphenyl)iodonium triflate (C), di(p-chlorophenyl)iodonium triflate (D), and di(p-bromophenyl)iodonium triflate (E), in the presence of CuCl and K2CO3 in CH2Cl2 for 3 h under refluxing

• ) with di(p-chlorophenyl)iodonium triflate (D) and then with TBAB and Na2S2O8, was carried out, as shown in Figure 1. Based on those results, the possible reaction pathway is shown in Scheme 4. The O-arylation of 3-aryl-2-propynoic acid 1 with diaryliodonium triflate in the presence of K2CO3 and CuCl

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• cyclization. Three-membered iodonium intermediates generated in the reaction course were expected to exhibit switchable regioselectivities [22]. This is because their cationic charge might be less localized on the carbon atoms α to the fluorine substituents, as compared to the aforementioned cationic

• elimination from 2a, 1,2-migration of the phenyl group, and deprotonation, followed by hydrolysis of the resulting doubly activated benzylic difluoromethylene unit (Scheme 2). Neither a combination of bis(pyridine)iodonium (IPy2BF4) and trifluoromethanesulfonic acid nor a combination of I2 and silver(I

• atom β to the fluorine substituents of the cyclic iodonium intermediate, which was derived from 1a and PyICl. This indicates that the cationic charge in the cyclic iodonium intermediate might be localized at the β-carbon atom because of stabilization by the proximal phenyl group [28]. Under the optimal

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• ) electrophilic addition of I2 to the alkyne moiety of this intermediate produces the iodonium intermediate B, (iii) isomerization of iodonium B gives intermediate C and (iv) a sequential intramolecular cyclization and HI elimination of C finally affords thiazolidines 27 [88]. Seeking for a greener approach

• mixture of 4H-1,3-thiazines 56 and 4,5-dihydrothiazoles 57. The mechanistic course of this reaction sequence is shown in Scheme 17 and involves the initial formation of the charge-transfer complex A between the iodonium ion and the triple bond. The 5-exo-dig cyclization of this intermediate gives rise to