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

• halofunctionalizations of acyclic monoterpenoids were performed using a combination of a hypervalent iodine(III) reagent and a halide salt. In this manner, the dibromination, the bromo(trifluoro)acetoxylation, the bromohydroxylation, the iodo(trifluoro)acetoxylation or the ene-type chlorination of the distal

• trisubstituted double bond occurred with excellent selectivity and moderate to good yields. Keywords: halogenation; hypervalent iodine; monoterpenes; Introduction In nature, mostly in marine environments, halogenated compounds are produced by means of various enzymes that rely on widely available halides as

• , which contains both iodine and chlorine atoms (Figure 1) [5]. This structural richness has fuelled the development of many synthetic strategies that take inspiration from these enzymatic machineries. A key aspect is to be able to mildly oxidize the halides into halenium equivalents in order to promote

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

• ; C–H activation; iodine; oxygenation; radicals; Introduction The oxidative activation of a C(sp3)–H bond in organic molecules to directly install various functional groups and new carbon–carbon networks is a topic of interest for researchers engaged in modern synthetic chemistry [1][2][3][4][5][6][7

• , reports aimed at realizing efficient and selective metal-free C(sp3)–H transformations are rather limited; however, investigations by several research groups are still ongoing [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Hypervalent iodine reagents are now widely accepted as a safe

• single-electron-transfer (SET) reactivities [33][34][35][36][37] allow selective activation of the benzylic C(sp3)–H bond for oxidative functionalization and coupling reactions. Initially, the SET oxidation ability of pentavalent iodine reagents, especially o-iodoxybenzoic acid (IBX), in benzylic

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

• . Keywords: acetoxylation; carboxylic acids; decarboxylation; hypervalent iodine; iodine; Introduction The decarboxylative functionalization of carboxylic acids and the derivatives thereof is an important transformation in organic synthesis. In recent years, increasing efforts have been devoted to the

• 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

• indicated that the reaction proceeds via the formation of an alkyl iodide and the corresponding iodine(III) species as key intermediates. In this context, we concluded that the use of such an oxidation system, combined with the judicious choice of solvent, would enable a decarboxylative C–O bond forming

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

• Cyrus Mowdawalla Faiz Ahmed Tian Li Kiet Pham Loma Dave Grace Kim I. F. Dempsey Hyatt Department of Chemistry and Biochemistry, Adelphi University, 1 South Ave., Garden City, NY, 11530, USA 10.3762/bjoc.14.91 Abstract The reactivity of benzyl hypervalent iodine intermediates was explored in

• 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

• incorporated into the product thus providing greater atom economy and a valuable functional group handle for further transformations. The altering of the RICR’s ortho-selectivity to form para-selective products with benzyl hypervalent iodine intermediates suggests a mechanism that involves hypervalent iodine

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

• -deficient and sterically encumbered aryl groups. Keywords: arylation; C–N coupling; diaryliodonium; hypercoordinate iodine; metal-free; Introduction Imides are important structural units in a range of approved pharmaceuticals and agrochemicals (Scheme 1a) [1]. Despite the general prevalence of imides, N

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

• Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu, Republic of Korea 10.3762/bjoc.14.89 Abstract Hypervalent iodine-mediated olefin functionalization provides a rapid gateway towards accessing both various heterocyclic cores and functional groups. In this regard, we have developed a Ritter-type

• . Keywords: amido-amidation; hypervalent iodine; isoxazoline; metal-free; oxyamidation; pyrazoline; Introduction Isoxazoline and pyrazoline-containing heterocycles are abundant in natural products and biologically active molecules [1][2][3][4][5]. Thus, these scaffolds are also important from the standpoint

• , diverse halonium sources have been utilized for the synthesis of isoxazolines via halocyclization. Furthermore, transition metal-, visible light, and hypervalent iodine-mediated oxidative cyclization protocols provide isoxazoline backbones bearing diverse substituents such as –SR, -CF3, -OH and halogens

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• ; cyclisation; fluorination; gauche effect; hypervalent iodine; oxazolines; Introduction Marine and terrestrial natural product bioprospecting has established a broad spectrum of structurally complex, bioactive metabolites containing the venerable 2-oxazoline unit [1][2]. This diversity is exemplified by the

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle

• Akira Yoshimura,
• Michael T. Shea,
• Cody L. Makitalo,
• Melissa E. Jarvi,
• Gregory T. Rohde,
• Akio Saito,
• Mekhman S. Yusubov and
• Viktor V. Zhdankin

Beilstein J. Org. Chem. 2018, 14, 1016–1020, doi:10.3762/bjoc.14.87

• , Duluth, MN 55811, USA, Division of Applied Chemistry, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan 10.3762/bjoc.14.87 Abstract A new bicyclic organohypervalent iodine heterocycle derivative of benziodazole was prepared by

• oxidation of 2-iodo-N,N’-diisopropylisophthalamide with m-chloroperoxybenzoic acid under mild conditions. Single crystal X-ray crystallography of this compound revealed a five-membered bis-heterocyclic structure with two covalent bonds between the iodine atom and the nitrogen atoms. This novel benziodazole

• ; biheterocycles; hypervalent iodine; iodine; oxidatively assisted esterification; Introduction In recent years, the interest in heterocyclic organohypervalent iodine compounds has experienced an unprecedented growth [1][2][3][4][5][6]. A variety of new hypervalent iodine heterocycles have been prepared, and

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition. Keywords: 1,4-diketones; enolates; enolonium species; hypervalent iodine

• -coupling by using cerium(IV) as a one-electron oxidant [11]. Importantly for the discussion of the present work, Wirth’s strategy relied on a hypervalent iodine [13][14][15] mediated oxidative cross-coupling. Although these processes add a further step to the process, carrying out the cross-coupling in an

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

• Takayuki Yakura,
• Tomoya Fujiwara,
• Akihiro Yamada and
• Hisanori Nambu

Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82

• iodine; iodobenzamide; organic catalysis; oxidation; oxone; Introduction The development of an efficient and environmentally benign organic synthesis is required for minimizing material use, energy consumption, and environmental pollution in the production of both bulk and fine chemicals. Oxidation is a

• fundamental and frequently used transformation in organic synthesis. Heavy metal-based oxidants such as chromium(VI), lead(IV), and mercury(II) have been extensively used for this purpose for a long time. However, these oxidants are highly toxic and produce hazardous waste. Recently, hypervalent iodine

• oxidants have been widely employed for oxidation in organic synthesis [1][2][3][4][5][6][7][8][9] because they are nonmetallic, less toxic, and easy to handle, and they allow mild reaction conditions in most cases. Pentavalent iodine reagents such as Dess–Martin periodinane (DMP, 1) [10] and 2

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

• -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

• Diaryliodonium salts, which are also known as diaryl-λ3-iodanes, are widely considered to be an important and practically useful class of hypervalent iodine compounds [1][2][3][4]. Diaryliodonium salts have found broad synthetic application as electrophilic arylating reagents in reactions with various

• based on the use of inexpensive, commercially available oxidants is an important and challenging goal. A vast majority of existing procedures involve the interaction of electrophilic hypervalent iodine(III) species with suitable arenes through ligand exchange processes [16][17][18][19][20]. The reactive

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• regioselective reaction of aryl- and α-substituted phenylallenes with the hypervalent iodine (HVI) reagent 1-chloro-1,2-benziodoxol-3-one. The reaction typically results in vicinal dichlorides, except with proton-containing α-alkyl substituents, which instead give chlorinated dienes as the major product

• . Experimental evidence suggests that a radical mechanism is involved. Keywords: allene; chlorination; hypervalent iodine; synthetic methods; vinyl chloride; Introduction Organochlorine compounds are vital as polymer precursors [1], as pharmaceuticals [2][3] and agrochemicals [4][5][6] and as functional

• vicinal-dichlorination of phenylallenes; however, no such chlorination reaction has yet been achieved [29][30][31][32][33][34]. Recent reports of reactions between hypervalent iodine reagents and phenylallenes have highlighted the possible product outcomes achievable through ionic and radical reaction

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

• Morifumi Fujita Koki Miura Takashi Sugimura Graduate School of Material Science, University of Hyogo, Kohto, Kamigori, Hyogo 678-1297, Japan 10.3762/bjoc.14.53 Abstract A series of optically active hypervalent iodine(III) reagents prepared from the corresponding (R)-2-(2-iodophenoxy)propanoate

• derivative was employed for the asymmetric dioxytosylation of styrene and its derivatives. The electrophilic addition of the hypervalent iodine(III) compound toward styrene proceeded with high enantioface selectivity to give 1-aryl-1,2-di(tosyloxy)ethane with an enantiomeric excess of 70–96% of the (S

• )-isomer. Keywords: 1,2-difunctionalization of alkenes; enantioselective synthesis; hypervalent iodine; oxidation; Findings Hypervalent aryl-λ3-iodanes have been widely used for metal-free oxidation with high selectivity in organic synthesis [1][2][3]. The reactivity of an aryl-λ3-iodane is controlled by

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -amidoalkyl-2-naphthols carried out in the presence of Lewis and Brønsted acid catalysts. As depicted in Table 1, entries 13–38, the applicability of p-toluenesulfonic acid (p-TSA) [27], montmorillonite K10 [30], Indion-130 [31], iodine (I2) [32], potassium dodecatungstocobaltate (K5CoW12O40·3H2O) [33

• up to 94% yields. Shinde et al. also published iodine catalysis carried out at room temperature in DCE [45]. Whereas long reaction times were needed in the latter process, good yields could be achieved under mild conditions. In additional publications listed in Table 1, entries 42–64, phosphorus

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• moderate to high yields. The present method could be applied to the HDA reactions of acylnitroso species with o-benzoquinones generated by the oxidative dearomatization of guaiacols. Keywords: acylnitroso; benzoquinone; cycloaddition; dearomatization; iodine(III); Introduction The hetero-Diels–Alder (HDA

• research on the syntheses of heterocycles by iodine(III)-mediated/catalyzed oxidative cycloaddition reactions [17][18][19], we have found that iodine(III) reagents are effective in the oxidation of N–O bonds of oximes in the cycloaddition reaction of in situ formed nitrile oxides [20][21]. Although Adam

• and Bottke’s group have demonstrated that (diacetoxyiodo)benzene (DIB) and iodosylbenzene are applicable to the ene reactions of acylnitroso species derived from hydroxamic acids [22], the iodine(III)-mediated oxidative cycloaddition reaction of hydroxamic acids with dienes is still unknown. Herein

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• . China 10.3762/bjoc.14.31 Abstract A solvent-free palladium-catalyzed ortho-iodination of acetanilides using N-iodosuccinimide as the iodine source has been developed under ball-milling conditions. This present method avoids the use of hazardous organic solvents, high reaction temperature, and long

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

• )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

• compounds in the pharmaceutical history indicates that some of these reagents have a heterocyclic skeleton which makes them suitable as drug candidates [29][30][31][32]. Among these compounds, our group is interested in investigating the biological activity of hypervalent iodine-type reagents [33

• ]. Hypervalent iodine compounds have been receiving a lot of attention lately due to their varied applications in organic synthesis [33][34][35][36][37][38][39][40]. A wide range of bioactive compounds make use of diaryliodonium reagents as a part of their synthesis [41][42][43]. On the other hand, there are

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

• coupling for pyrroles using a hypervalent iodine reagent and a stabilizer for pyrrolyliodonium intermediates (Scheme 1c) [9]. The reactions readily provided a variety of desired coupling products in good yields. In general, the mechanism of these arylations was postulated by generating aryl radicals with

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

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• catalysts like L-proline, InCl3 and ZrCl4 also resulted in the formation of o-hydroxyphenylpyrazolo[3,4-b]pyridine derivatives 85 but no product was formed in iodine- and acetic acid-catalyzed reactions (Scheme 22). Huang et al. [70] investigated a three-component reaction of β-ketonitriles 15, 5

• 200 from the cyclocondensation of 5-amino-1-(2,4-dinitrophenyl)-1H-pyrazole-4-carboxamide (199) with aromatic aldehydes in the presence of iodine in acetonitrile (Scheme 55). The synthesized pyrazolo[3,4-d]pyrimidines were evaluated for antibacterial activities. Venkatesan et al. [132] also used 4

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• -membered-ring transition state. Note that the presence of an olefin moiety in the product promised further conversion to other types of CF3-containing molecules. Later, the group of Wang [50] employed cheap copper chloride as the catalyst and a hypervalent iodine(III) reagent 1j as both the oxidant and the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• isomerized in the presence of an Ir complex and the resulting prop-1-enyl group was then removed by aqueous iodine to yield hemiacetal 30 which was stereoselectively phosphorylated by reaction with lithium hexamethyldisilazide (LHMDS), and subsequent treatment with tetrabenzyl pyrophosphate. Final

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -cyanotrifluoromethylations [22] of alkenes under photoredox catalysis. These reactions proceeded through a formyl or a cyano group migration triggered by the addition of the trifluoromethyl radical onto the alkene moiety. Both methodologies were developed using Togni’s hypervalent iodine reagent as the CF3 source, but it

• introduction of the CF3 moiety on enol acetates (Scheme 29) [37]. Anecdotally, CF3SO2Cl was evaluated for the trifluoromethylation of allylsilanes, but, disappointingly, gave lower yields than Togni’s hypervalent iodine reagent [38]. More recently, Balaraman and co-workers studied extensively the reaction of β

• through the nucleophilic attack of the sulfur atom by the iodine counter anion, leading to the formation of intermediate 43, which ultimately furnished CF3SOCl, regenerating I2 in the process. A second reduction then took place, followed by the electrophilic trifluoromethylsulfenylation step. According to

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

• , CF3H, as an ideal source of trifluoromethide offered new horizons for atom-economical, low-cost trifluoromethylation reactions. With regard to electrophilic CF3 donors, S-(trifluoromethyl)sulfonium salts developed by Yagupolskii and Umemoto and hypervalent iodine(III)-CF3 reagents developed by Togni

• reactions with K2S2O8, I2O5 or a hypervalent iodine reagent, and (iii) photochemical activation. Most of the works concerned cascade intramolecular reactions in which a C–C bond is formed after the initial trifluoromethylation. Therefore, Lipshutz and co-workers reported a copper-catalysed intramolecular

• persulfate by hypervalent iodine oxidants such as iodobenzene diacetate (PIDA, Scheme 28) [49], or iodobenzene bis(trifluoroacetate) (PIFA) [50]. Fu and co-workers proposed the reaction mechanism depicted in Scheme 28. PIDA reacted with CF3SO2Na under heating conditions to produce two radicals: CF3• along

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• rearrangement of the primary O-imidoylation reaction product 21 (Scheme 15). The second method (procedure B) is based on the reaction of ylides with imidoyl iodides that are synthesized in situ from the corresponding imidoyl chlorides via the exchange of chlorine for iodine in the presence of sodium iodide