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

• of Pd(OAc)2 in THF, and affords the dibenzoalkylidenefluorene 47 in an excellent 88% yield (Scheme 16). Ten years later, Huang, Wen and co-workers have demonstrated that, in the presence of both a terminal alkyne and a boronic acid, various cyclic diaryl-λ3-iodanes undergo a transition-metal

• and migratory addition into the proximal alkyne. Transmetalation of the vinylpalladium with the boronic acid and reductive elimination finally leads to alkylidenefluorenes 49. This multicomponent strategy allows the variation of the alkyne, the boronic acid and the diaryliodonium salts, but the use of

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• products in high yields (81–96%) and enantioselectivities (93–96% ee). Good yields (82–85%) and high enantioselectivities (92–96% ee) were also obtained for disubstituted arylboronic acids. Even a heteroaromatic boronic acid (Ar = 2-thienyl) was tolerated, providing the corresponding product in excellent

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• detected. However, both boronic acid homocoupling (ArAr) and boronic acid oxidation (ArOH) occurred to a small extent as indicated by HPLC. As the side product formation mainly occurs when the bromoarene coupling partner gets depleted, highest reaction selectivity (up to 99.5% [37]) can be achieved by

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

• promise for the future. Copper-catalyzed trifluoromethylation of boronic acid derivatives Boronic acid derivatives are common building blocks in organic chemistry due to its commercial availability, and stability to heat, air, and water. Several examples of trifluoromethylation of boronic acid derivatives

• with nucleophilic, electrophilic or radical trifluoromethylation reagents were reported. Trifluoromethylation of boronic acid derivatives with nucleophilic trifluoromethylation reagents Protodeborylation was found to be the main side reaction in the copper-catalyzed trifluoromethylation of arylboronic

• primary and secondary alkylboronic acids underwent the trifluoromethylation well under different optimized conditions. Trifluoromethylation of boronic acid derivatives with electrophilic trifluoromethylation reagents CF3+ reagents were also explored in the trifluoromethylation of boronic acid derivatives

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

• A, transmetallation of the boronic acid with the active Cu(II) species 73 gave the arylcopper(II) complex 74, which reacted with CF3• to afford the arylcopper(III) complex 75. Next, a reductive elimination gave the trifluoromethylated product with release of the Cu(I) complex 76 that was re-oxidised

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• al. explored the use of ortho-dihydroxyboryl-substituted benzyl thioglycosides as a delivery method for the leaving group-based intramolecular glycosylation [129]. They hypothesized that if boronic acid-derived donor 100 is activated in the presence of glycosyl acceptor 101, the boronic ester 102

• alcohol showed good selectivity (α/β = 4.8:1) when boronic acid and NBS were employed. Control experiments with a thiophenyl or a thiobenzyl leaving group showed lower stereoselectivities and a slight reduction in yields. The addition of triflic acid or silver triflate resulted in a significant reduction

• mediated IAD. DISAL as the leaving group that favors the intramolecular glycosylation pathway. Boronic acid as a directing group in the leaving group-based glycosylation method. Acknowledgements The authors are indebted to the National Institute of General Medical Sciences (GM111835 and GM120673) for

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• alkaloids one common building block, (4-methoxy-2-(methoxycarbonyl)phenyl)boronic acid pinacol ester (9) [24], could be applied, since the alkaloids of interest all bear the methoxy group at C-9. Suzuki cross-coupling reaction of the iodinated isoquinolines 8a–c with this boronate under Pd(PPh3)4 catalysis

• pyridine nitrogen), can very well promote a directed remote metalation. To test our hypothesis, we performed two more D2O quenching experiments with naphthalene analogues of esters 10 and amide 12. The methyl ester analogue 15 was obtained by Suzuki cross-coupling of naphthalene-1-boronic acid (13) and

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• reaction (Table 2, entry 11). No product was obtained when boronic acid pinacol ester 6 and borate salt 7 were used as a coupling partner (Table 2, entries 12 and 13) [35]. Dimethoxyethane (DME) and 1,4-dioxane as ethereal solvents did not improve the yields (Table 2, entries 14 and 15). Decreasing the

• ). No product was obtained when n-butylboronic acid (4h) was used as an aliphatic boronic acid (Table 3, entry 11). Subsequently, the effect of substituents at the 2-position, which was derived from the carboxylic acids, was tested. Aryl substituents possessing both electron-withdrawing and electron

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• to maximize the formation of the diazo compound (Scheme 18) [87]. Starting from this initial investigation, Ley and co-workers developed an elegant application of this strategy for a sequential formation of up to three C–C bonds in sequence, by an iterative trapping of boronic acid species. The

• sequence starts with the reaction of diazo compound 20, generated under flow conditions, and boronic acid 19 (Scheme 19). Further sequential coupling with diazo compounds 21 and 22 led to boronates 23 or protodeboronated products 24 at the end of the sequence (Scheme 19). With the aim to exploit the

• versatility of this approach, Ley and co-workers reported the allylations of carbonyl electrophiles such as aldehydes using the above reported strategy for the generation of allylboronic acids. The flow protocol considers the reaction of diazo compounds 25 (generated in flow) with boronic acid 26 and aldehyde

Formose reaction controlled by boronic acid compounds

• Toru Imai,
• Tomohiro Michitaka and
• Akihito Hashidzume

Beilstein J. Org. Chem. 2016, 12, 2668–2672, doi:10.3762/bjoc.12.263

• macromolecular boronic acid compounds, i.e., sodium phenylboronate (SPB) and a copolymer of sodium 4-vinylphenylboronate with sodium 4-styrenesulfonate (pVPB/NaSS), respectively. The boronic acid compounds provided different selectivities; sugars of a small carbon number were formed favorably in the presence of

• SPB, whereas sugar alcohols of a larger carbon number were formed preferably in the presence of pVPB/NaSS. Keywords: boronic acid compounds; formose reaction; sodium phenylboronate; sodium 4-vinylphenylboronate/sodium 4-styrenesulfonate copolymer; sugar alcohols; sugars; Findings When an aqueous

• optimizing the conditions of the formose reaction [6][7][8][9][10][11][12][13][14][15]. However, the selective formose reaction is still an important subject of investigation [16]. It is known that boronic acid compounds form esters with diols, e.g., sugars [17][18]. Boronic acid compounds may thus stabilize

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• -mediated processes for stereoselective functionalization of unactivated C−H bonds is currently undergoing in our laboratory. Experimental General procedure for the sp3 C–H arylation of THIQs with boronic acid derivatives (Figure 1). A V-shaped 10 mL Biotage reaction vial was charged with [Ir(ppy)2(dtbbpy

• concentrated and purified by column chromatography or preparative thin-layer chromatography on silica gel to yield the corresponding arylated compound 3. Dibromomethane was used as internal standard for 1H NMR analysis. Variation for enantioselective sp3 C–H arylation of THIQs with boronic acid derivatives

High performance p-type molecular electron donors for OPV applications via alkylthiophene catenation chromophore extension

• Paul B. Geraghty,
• Calvin Lee,
• Jegadesan Subbiah,
• Wallace W. H. Wong,
• James L. Banal,
• Mohammed A. Jameel,
• Trevor A. Smith and
• David J. Jones

Beilstein J. Org. Chem. 2016, 12, 2298–2314, doi:10.3762/bjoc.12.223

• , Melbourne, Australia 10.3762/bjoc.12.223 Abstract The synthesis of key 4-alkyl-substituted 5-(trimethylsilyl)thiophene-2-boronic acid pinacol esters 3 allowed a simplified alkylthiophene catenation process to access bis-, ter-, quater-, and quinquethiophene π-bridges for the synthesis of acceptor–π-bridge

• donors via chain extension catenation of alkylthiophenes. We have used commercially available 3-butyl-, 3-hexyl- and 3-octylthiophene to form the key intermediate TMS-alkylthiophene boronic acid pinacol esters (3) in high yield on a large scale and in high purity as they can be purified by distillation

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• the Suzuki–Miyaura coupling [11]. A retrosynthetic analysis (Figure 3) of extended mono-functionalized triazinetricarboxylic acids 2 calls for tris(4-bromoaryl)-1,3,5-triazines 3 and boronic acids 4 with an additional carboxylic acid functionality. The respective methyl carboxylate of boronic acid 4

• ) MeOH/H2SO4, MeOH, 16 h, reflux, 94%, c) Me2SO4, K2CO3, acetone, 3 h, reflux, quant., d) MeI, K2CO3, DMF, 16 h, room temperature, 83%, e) NaOH, H2O, MeOH, 6 h, room temperature, 66%, f) SOCl2, DMF (cat.), 2 h, reflux, not isolated. Triple Suzuki–Miyaura coupling between tribromotriazines 3 and boronic

• acid 15 and subsequent hydrolyses of the esters 16. Conditions: a) Pd(PPh3)4, K3PO4, dioxane, H2O, 48 h, reflux, 16b: 90%, 16c: 73%, b) Pd/C, H2, 5 bar, CH2Cl2, 5 d, room temperature, 16d: 77%. c) 17b: LiOH/H2O/dioxane, 48 h, room temp, 96%; 17c: LiOH/H2O/THF, 24 h, 60 °C, quant.; 17d: H2O/THF, 24 h

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• boronic acid used was decreased to 1.4 equiv and 1.1 equiv, respectively (entries 12 and 13, Table 1). Changing the temperature from 20 °C to 50 °C did not greatly affect the yields obtained, with 40 °C giving the most promising result (entries 14–16, Table 1). However, it was observed that less

• acetate. The amount of triethylamine was not varied as its quantity was required to ensure the boronic acid remained soluble in the dichloromethane solvent. To determine the time needed to reach steady state in the reactor, samples were periodically collected (every 2 min via an autosampler) and analysed

• acid. A column of QP-DMA, a polymer-supported tertiary amine base, was placed in-line after the “tube-in-tube” reactor (Figure 1). It was found that this was sufficient to remove the majority of boronic acid without affecting the yield of the product (Figure 3). Ultimately as the products were required

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• prepared by the methods described above are excellent and versatile precursors for transition-metal-catalyzed coupling reactions [32][53][54][55][56][57]. Standard conditions for a Suzuki coupling smoothly transform compound 5a and a boronic acid derivative into the expected 4-tolyl-substituted derivative

• 9 and the higher substituted precursor 5b was converted into compound 10 by employing an acetyl-substituted boronic acid derivate in very good yield (Scheme 5). Compound 10 was prepared in order to investigate its capability to form a C3-symmetric star-shaped product by cyclocondensation of the

The role of alkyl substituents in deazaadenine-based diarylethene photoswitches

• Christopher Sarter,
• Michael Heimes and
• Andres Jäschke

Beilstein J. Org. Chem. 2016, 12, 1103–1110, doi:10.3762/bjoc.12.106

• benzenesulfonyl chloride, resulting in a four-fold increased yield of 6 compared to the original route. The other part of the diarylethene, namely the cyclopentenyl bridge with the attached substituted thiophene ring was furnished as shown in Scheme 3 and activated as boronic acid pinacolate ester. Suzuki

• of the closed ring form was measured over 1 h. Synthesis of 7-deaza-2’-deoxyadenosine photoswitches with one and two methyl groups via Suzuki cross-coupling [45]. Optimized route for synthesis of 7-deaza-7-iodo-8-methyl-2’deoxyadenosine (9). Synthesis of the boronic acid pinacolate esters. Absorption

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• gave excellent selectivity at room temperature (Scheme 5). When this substrate was subjected to optimized conditions for the boronic acid C–H coupling, the corresponding singly ortho-arylated product was obtained in 97% yield solely as the 2-aryl isomer, as confirmed by 1H NMR and X-ray crystallography

• acidity of the metal center. This is a noteworthy advantage associated with the use of cationic palladium(II) catalysts. Finally, BQ oxidizes the Pd(0) that is reductively eliminated from the HPd(II)+BF4− formed to regenerate the active cationic palladium species Pd2+(BF4)2−. C–H boronic acid coupling

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• %) as a co-solvent with toluene. On the other hand, the attempted coupling of compound 41 with 2-nitrophenylboronic acid and (2-chloro-6-methoxyphenyl)boronic acid failed. Despite more drastic conditions (xylene, DMF, 145 °C, 48 h, 8 mol % Pd(OAc)2/16 mol % S-Phos) any amount of 3,5-bis(2-nitrophenyl

• (41) and (2-methylphenyl)boronic acid (37) in dioxane in the presence of PdCl2(dppf) × CH2Cl2, K3PO4, at 65 °C, provided only a mixture of debrominated and dechloro/debrominated phenylpyridines with only little quantities of the desired products 70, and 68 (<5%), respectively (estimated by GC–MS

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• ) complex with 1,3-dicyclohexylimidazol-2-ylidene is found to efficiently catalyze the borylation of arenes and heteroarenes. The resulting aminoborylated products can be converted to the corresponding boronic acid derivatives simply by treatment with suitable diols or diamines. Keywords: boronic acid; C–H

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• Supramolecular Chemistry was through the self-assembly of phospholipid membranes to form vesicles for which we were developing unimolecular and self-assembling transporter molecules. The next stage of my development as a scientist was in Japan with Seiji Shinkai where in a “Eureka” moment, the boronic acid

• of Victoria, I knew very little about Japan and almost-nothing about the Japanese Language. (Karate had taught me to count from 1 to 10). Having just finished a project with a lot of multistep synthesis, I was immediately drawn to projects as part of the boronic acid research group. The boronic acid

• fluorescent photoinduced electron transfer (PET) pH sensors developed by A. P. De Silva (Figure 3) [17] in order to develop a fluorescence sensor for saccharides [18]. Thus creating a system where the neighbouring nitrogen lowered the working pH of the boronic acid and provided a fluorescence signalling

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• Inouye and Shinkai [60][61]. IDAs are now one of a handful of standard approaches to creating optical sensors [62]. Our group optimized the citrate receptor design by incorporating a single boronic acid (11) [63] and measured citrate in soda pops [64], vodkas [65], and most recently showed that such

• the boronic acid in a spatial manner to best complement the citrate “key” to the receptor “lock” (11). In other studies, using a lock and key design approach led to very selective and high affinity receptors for heparin [68][69] and 2,3-bisphosphoglycerate [70]. Although reading the label of a Fresca

N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions

• Senem Akkoç,
• Yetkin Gök,
• İlhan Özer İlhan and
• Veysel Kayser

Beilstein J. Org. Chem. 2016, 12, 81–88, doi:10.3762/bjoc.12.9

• -butylphenylboronic acid which is a derivative of phenylboronic acid (Table 3, entries 5–8). All compounds were found to be very effective for this coupling reaction and the product yield was between 94–100%. The C–C bond formation of thianaphthene-2-boronic acid with 4-chloronitrobenzene using an in situ formed Pd

• demonstrated low activity in the coupling of thianaphthene-2-boronic acid with 4-chloronitrobenzene (Table 3, entries 9–12; Table 4, entries 9–12). In C–C bond-forming reactions of different substrates with 2,5-dimethoxyphenylboronic acid and thianaphthene-2-boronic acid, complex 7 was found to be a good

• bromidesa,b. Suzuki–Miyaura cross-coupling reaction of phenylboronic acid with aryl chloridesa,b. Suzuki–Miyaura cross-coupling reaction of boronic acid derivatives with aryl halidesa,b. Suzuki–Miyaura cross-coupling reaction of boronic acid derivatives with aryl chloridesa,b. Supporting Information

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• of CnFn+1Cu reagent were used. dPinacolboronate ester (Bpin) was used instead of boronic acid. eYield was determined by 19F NMR analysis using BTF as an internal standard. Trifluoromethylation with silylated hemiaminal of fluoral. Catalytic trifluoromethylation with a fluoral derivative. The scope of

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• ; boronic acid; miniamyloids; NMR spectroscopy; peptides; Introduction Aβ peptides spontaneously form amyloid fibrils which are a major component of Alzheimer plaques [1]. The cooperative thermodynamically-driven process of fibril formation has an induction period which depends on the conditions of amyloid

• concept of tailoring the length of the peptide boronic acid and a polyol template is shown in Figure 2. Results and Discussion The shortest known functional expansion of the amyloidogenic Aβ-peptide is the β-amyloid (17–21) Leu-Val-Phe-Phe-Ala [20] which was investigated as both a C-terminal 1 and as an N

• -terminal boronic acid 2. Peptide boronic acids of type 1 were synthesized on polymer-bound diethanolamine (PS-DEAM resin), according to the protocol in Supporting Information File 1, Figure S1 [21]. The electron-poor boronic acid 2, which was expected to be more reactive in boronic ester formation, was

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• . Suzuki coupling efficiency in DMF (entries 2 and 3, Table 1) was not as high as Stille coupling (entry 1, Table 1). Suzuki coupling of intermediate 26 with 1-naphthylboronic acid, pyridine-4-boronic acid, pyridine-3-boronic acid and 5-propynylpyridine-3-boronic acid (Method II) (entries 4, 6, 8, and 10