Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• cyclization of N-propargylamides and the second involves the cyclization of β-amidoketones. These are proposed to proceed through different mechanisms and have different substrate scopes. Keywords: amides; catalysis; cyclization; hypervalent iodine; isoxazolines; Introduction Hypervalent iodine reagents are

• ][26][27][28][29]. Saito and co-workers have reported the cyclization of propargylamides to form oxazoles rather than oxazolines under stoichiometric and, more recently, catalytic hypervalent iodine conditions [30][31]. Various other methods for the cyclization of unsaturated amides have been reported

• of hypervalent iodine in catalytic procedures. Studies concerning the elucidation of reaction mechanisms are ongoing and will be reported in due course. Experimental General procedure for 2-iodoanisole-catalyzed cyclization of N-propargylamide 4 or β-amidoketone 5: Propargylamide 4 (1 equiv) or β

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• investigated the phase-transfer catalysed α-cyanation of ketoesters 1 using hypervalent iodine-based cyanide transfer reagents [97]. Hereby we observed the in situ oxidation of the PTC counter anions (Br− or I−) and subsequent α-halogenation of 1. We tried to employ and optimise this procedure, but without any

• alkaloid-based organocatalysts to carry out the α-trifluoromethylthiolation of β-ketoesters 1 by using the hypervalent iodine-based CF3S-transfer reagent 36 in an asymmetric fashion. Very interestingly, they realized that for indanone-based ketoesters 1 (with n = 1) simple cinchona alkaloids themselves

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• tryptophan derivatives with appropriate aldehydes. A hypervalent iodine reagent, iodobenzene diacetate was used in stoichiometric quantities to facilitate both oxidative decarboxylation/dehydrogenation of 108–110 to afford the desired natural products 111–113 (Scheme 42). Conclusion Substantial amount of

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• for their synthesis have been developed. Among them are reactions between lithium or sodium acetylides and electrophilic selenium reactants [23]. The use of hypervalent iodine(III) species [24] or alkynyl bromides with RSeLi [25] as nucleophilic selenium species or the reaction of alkynyl bromides

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• Organoborates M[RBX3] (X = OAlk, F) are widely used in various fields of chemistry [1][2][3][4][5][6][7][8][9][10][11][12]. Their polyfluorinated analogues M[RFBX3] have been used as starting reagents in the synthesis of compounds of hypervalent bromine [13], iodine [14][15][16] and xenon [17][18][19][20][21

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• benzaldehyde and o-phenylenediamine to obtain 2-phenyl-1H-benzimidazole (1a) are known. However, they afforded moderate yields requiring longer reaction times in the presence of air (Table 1, entries 27 and 28) [38][39]. Product 1a was also obtained in a shorter reaction time using hypervalent iodine as

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• methylpalladium(II) complexes like 13 (Scheme 3). It has previously been shown that the oxidation of palladium(II) complexes is feasible [42]. Several papers reported the successful oxidation of Pd(II) complexes by hypervalent iodo reagents [43][44][45][46][47][48]. Sanford, Arnold and co-workers could also show

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• is highly attractive, but the use of a carbon linker is usually required. Herein, we report the gold-catalyzed direct alkynylation of tryptophan in peptides using the hypervalent iodine reagent TIPS-EBX (1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one). The reaction proceeded in 50–78% yield

• under mild conditions and could be applied to peptides containing other nucleophilic and aromatic amino acids, such as serine, phenylalanine or tyrosine. Keywords: alkynes; C–H functionalization; gold catalysis; hypervalent iodine; peptides; Introduction Alkynes have always been important building

• the Sonogashira reaction, which requires modified non-natural amino acids [32][33]. In 2013, our group reported the alkynylation of thiols using the hypervalent iodine reagent TIPS-EBX (1a, 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one) (Scheme 1A) [34]. The reaction was almost

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• -oxazolidinone motifs (Scheme 1D) [16]. Metal-free intermolecular oxyamination reactions have also been accomplished; examples were reported by the Zhu lab with the use of peroxides [17] and by the Studer lab with the use of hypervalent iodo-azide reagents [18]. Furthermore, the intramolecular oxyamination of

• olefins with a tethered amino or oxygen functionality has been achieved for the construction of a variety of 1,2-oxyamino products, using palladium [19][20], platinum [21], gold [22], copper [23][24][25][26], free-radical initiators [27][28][29], hypervalent iodine [30], and electrochemical oxidation [31

Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

• Kazuhiro Hata,
• Hideto Ito,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2015, 11, 2737–2746, doi:10.3762/bjoc.11.295

• such oxidative reaction conditions. For example, triphenylphosphine is easily oxidized to triphenylphosphine oxide by a hypervalent iodine reagent that has been used as an oxidant for gold-catalyzed C–H arylation [69]. Appropriate ligands that are tolerant to the oxidative conditions would offer

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• -aryl migration step. This was mediated by a hypervalent iodine reagent, PhI(OAc)2 (13), conducted in trimethyl orthoformate (14, TMOF) and methanol (Scheme 2). The direct saponification of the resulting rearranged methyl ester with an excess of base thus completed the telescoped flow synthesis of

• the existing manufacturing routes which have been highly refined and optimised [49][50][51]. Although modern reagents such as hypervalent iodine and triflic acid represent very valuable additions to the chemists’ repertoire they are also inherently expensive and difficult to source at scale. In

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• other than in pHPMA (3.4) and hPG (3.7 nm). The larger distance in hPG might be related to the hypervalent morphology of this carrier, which possibly limits the proximity of attached ligands. Expected values of averaged (over time and atoms) radial distributions (correlating with normalized mean

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• species, various hypervalent transition metal–oxo and metal–peroxo species, dihalogens, hypohalites, and enzymes. The first direct electrochemical oxidation was reported only in 2005. The electrochemical oxidation of cholesterol may occur at the C3-hydroxy group, at the C5–C6 double bond, at the allylic

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• large steric demand of encapsulating fenchane units renders the phosphorus atom nearly inaccessible by nucleophilic reagents, but only for BIFOP–Cl. In addition to the steric effect, a hypervalent P(III)–O interaction as well as an electronic conjugation effect causes the high reactivity of O–BIFOP–Cl

• (Scheme 4) suggest a neighbor-group effect through an O-lp donor to σ*P–Cl acceptor interaction, supporting chloride substitution (Figure 5, Scheme 4). Hypervalent P(III)–O interactions with similar P–O distances are documented for five membered rings [47][48] as well as for acyclic systems [49]. The

• hydrolysis, O–BIFOP–Cl (3) reacts instantly with water, leading to cyclofenchene 6. X-ray studies revealed that the increased reactivity of the intermediate carbenium ion and cyclopropane formation is due to a steric effect caused by the shielding of the fenchane groups and a hypervalent P(III)–O interaction

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• ][22][23][24]. Reports of organometallic additions to THIQs in this context are limited to aryl [25][26][27] and alkynyl [22][28][29][30] nucleophiles and the substrate scope is generally limited to N-aryl THIQs [31]. However, Li reported a hypervalent iodine mediated N-aryl THIQ oxidation which

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• hypervalent iodine reagents [9][10][11][12], and homogeneously or heterogeneously catalyzed multicomponent reactions [13][14]. Moreover, radical cyclizations predominantly conducted using Bu3SnH in the presence of azobisisobutyronitrile (AIBN) play a crucial role [15][16]. However, all these methods require

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• immediately. Although a broad range of (hetero)arenes undergo C–H-arylation under copper catalysis, heterocycles possessing acidic N–H bonds react at the nitrogen preferentially [52][53]. Moreover, directing groups such as acetyl (in combination with a hypervalent iodine aryl source) [42], or 2-pyridinyl

Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl)-3H-1λ³,2-benziodaoxol-3-one

• Nico Santschi,
• Roman C. Sarott,
• Elisabeth Otth,
• Reinhard Kissner and
• Antonio Togni

Beilstein J. Org. Chem. 2014, 10, 1–6, doi:10.3762/bjoc.10.1

• -(trifluoromethyl)-3H-1λ3,2-benziodaoxol-3-one (3), a hypervalent-iodine-based electrophilic trifluoromethylating reagent, is described. Whereas considerations based on cyclic voltammetry and X-ray structural properties would predict an inferior reactivity when compared to the non-nitrated derivative 2, 19F NMR

• trifluoromethylation; 19F NMR kinetics; nitration; organo-fluorine; Introduction Since the advent of the hypervalent-iodine-based electrophilic trifluoromethylation reagents 1 and 2 in 2006 they have found widespread application in organic synthesis (Figure 1) [1][2][3][4]. Recently, increasing interest has been

• around 300 nm, a strong hypsochromic shift of roughly 40 nm is observed for 3. This can be explained by the installation of the hypervalent bond and the presence of the strongly electron-withdrawing CF3 group, as also indicated by the carbon chemical shift analysis. Compounds 6 and 3 were also

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• derivatives 5a–o. These incipient products undergo feasible Dimroth rearrangement to furnish the isolated [1,2,4]triazolo[1,5-c]pyrimidines 6a–o in moderate to high yields. Keywords: cyclization; hydrazones; hypervalent iodine; oxidation; rearrangement; [1,2,4]triazolo[1,5-c]pyrimidines; Introduction The

• an efficient synthesis of new [1,2,4]triazolo[1,5-c]pyrimidine derivatives from hypervalent iodine (IBD)-mediated oxidative cyclisation of aldehyde pyrimidinylhydrazones and consecutive Dimroth rearrangement in relatively good yields under very mild conditions. Results and Discussion The

• aldehydes, affording the corresponding hydrazones 4. In general, aromatic aldehydes provided higher yields than aliphatic aldehydes. In recent years, organo hypervalent iodine reagents have drawn considerable interests as versatile and environmentally benign oxidants with many applications in organic

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• ) redox couples could be accessed using external stoichiometric oxidants (i.e. Selectfluor or hypervalent iodine compounds) [73]. As schematically shown in Figure 1 this approach allows a double functionalization of simple alkenes with subsequent formation of new C–X and C–C bonds in a single catalytic

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• reaction conditions showed that cesium fluoride proved the best base. PhI(OAc)2 was the preferred oxidant over other hypervalent iodine compounds or sources of F+ or CF3+; additionally, the presence of a bis(oxazoline) as a ligand was beneficial to the reaction, as well as that of TEMPO to prevent

• -releasing groups at the 5-position, and considering the regioselective 3-functionalization of N-methylindole, the authors proposed the following catalytic cycle: 1) electrophilic palladation of indole, 2) oxidation of the resulting Pd(II) species by the combination of the hypervalent iodine reagent and

• trifluoromethylation; indeed, all of them used the same electrophilic CF3 source, namely Togni’s benziodoxolone reagent. M. Sodeoka and coworkers reported on the trifluoromethylation of indoles with Togni’s hypervalent iodine reagent in the presence of catalytic copper(II) acetate [82]. No additives were necessary

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• available reagents have been employed under metal-free conditions. A group [27] reported that the hypervalent iodine reagents (diacetoxyiodo)benzene (DIB) and phenyliodine bis(trifluoroacetate) (PIFA) could successfully promote the oxidation of aldoximes to the corresponding nitrile oxide. Those reagents

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• % yield (Table 1, entry 10). Using 4.0 equiv of Umemoto’s reagent 3b instead of 3a gave the product 2a in 27% yield (Table 1, entry 12). S-(Trifluoromethyl)benzothiophenium salt 3c [24], trifluoromethylsulfoxinium salt 3d [25], and hypervalent iodine(III) CF3 reagent 3e [26] did not proceed or provided

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• Yifan Li Jerome Waser Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH4306, 1015 Lausanne, Switzerland 10.3762/bjoc.9.204 Abstract The direct alkynylation of benzofurans was achieved for the first time using the hypervalent iodine

• successful in the case of the more complex drug 8-methoxypsoralen (8-MOP). Keywords: alkynylation; benzofurans; cooperative catalysis; direct functionalization; gold catalysis; hypervalent iodine; Introduction Benzofurans are important heterocycles frequently encountered in both bioactive compounds and

• the use of ethynylbenziodoxolones, which are cyclic hypervalent iodine reagents [22][23]. Nevertheless, the conditions we have used for other heterocycles gave only very low yields in the case of benzofurans. Herein, we would like to report the first catalytic direct C2-alkynylation of benzofurans 7

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• a product formation, but the combined use of a catalytic amount of OC-49·Cl (5 mol %) and a stoichiometric quantity of Me3SiCl led to the desired ring-opening product in low yield (35%) and moderate enantioselectivity (65% ee). The control experiments indicated that the hypervalent silicate ions