Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• %; ii) N-bromosuccinimide, chloroform, 60 °C, yield: 87%; iii) (4-hydroxyphenyl)boronic acid, Pd(PPh3)4, K2CO3, CsF, toluene/THF/H2O, reflux, 8 h, yield: 70%; iv) K2CO3, 1,5-dibromopentane, acetone, 80 °C, yield: 67%; v) NaN3, DMF, yield: 84%; vi) paraformaldehyde, BF3·OEt2, 1,2-dichloroethane, yield

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• suitable agents for boron neutron capture therapy (BNCT) became a major need. Among many others, sugar boronic acids have recently attracted attention as boron carriers. Herein we report the synthesis and preliminary biological studies of two new sugar analogues containing a boronic acid at the anomeric

• position. The analogues were obtained by hydroboration of proper open-chain terminal alkenes that, after quenching with water, spontaneously afforded cyclic boronic acids with hemiacetal-like structures. Keywords: antitumor agents; boron neutron capture therapy; boronic acid; hydroboration; sugar analogue

• . Galactose and fructose also allow tumor growth in the absence of glucose. Boronic acid derivatives have gained interest in the last years in different fields such as the development of enzyme inhibitors, drug delivery polymers, saccharide sensors and as boron carriers for BNCT, e.g., amino acid derivatives

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• blocks especially for natural product synthesis [36][37][38][39][40]. Therefore, we used the perfluorophenyl boronic acid catalyst in the reaction between 2,3,4,6-tetra-O-acetyl-D-glucal (1a) and benzyl alcohol, n-butyl alcohol, cyclohexyl alcohol and p-toluenethiol (Figure 2). Gratifyingly, the reaction

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• as the conjugation of steroids to amino acids, peptides and carbohydrates. We demonstrate that steroids are available with almost all types of MCR reactive functionalities, e.g., carbonyl, carboxylic acid, alkyne, amine, isocyanide, boronic acid, etc., and that steroids are suitable starting

• or by the N-terminus to the estrone-derived boronic acid 64 using the on-resin Petasis-3CR in the presence of dihydroxyacetone [68]. Peptido-steroids 65 and 67 were obtained in good overall yields after released from the resin using the cocktail TFA/H2O/triisopropylsilane (TIS), albeit the

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• only viable alternative to bipyridine (Table 1, entry 7), with other ligands commonly used in copper-catalyzed reactions such as proline and 2,2,6,6-tetramethyl-3,5-heptanedione giving yields under 15%. Reducing the number of equivalents of boronic acid 25 and sodium carbonate was found to be well

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• asymmetric products 131 is mainly obtained, where the aromatic group coming from the boronic acid partner settles far from the carbonyl group. Methoxy, nitro, chloro and acetoxy groups of the aromatic moiety can be located at the ortho, meta and para positions, although 2-nitro derivatives gave low yields or

• palladium-catalysed reactions (Scheme 38). The first one is a Sonogashira coupling reaction between the terminal alkyne of propiolamide 128 and aryl iodide 129, which is preferred to the Suzuki–Miyaura reaction between aryl iodide 129 and boronic acid 130 present in the reaction mixture. Then, an internal

• , presumably by changing the anionic character of the palladium complex to cationic in intermediate 135. Finally, the Suzuki–Miyaura coupling of palladium salt 135 with boronic acid derivative 130 would provide the final oxindoles 131 or 132. Finally, is worth mentioning an example of a multicomponent

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• )/H2O (95:2.5:2.5) for 2 h affording the linear boronopeptide H-Phe(4-B(OH)2)-Ala-Gln-Leu-Gln-Phe(4-I)-βAla-Gln-OpNB in >99% purity, which was characterized by mass spectrometry. The boronic acid function resulted from hydrolysis of the boronic ester during HPLC analysis as shown by mass spectrometry

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• . The strategy to “oxidize” the 3-position of AQs via iodination, lithium–halogen exchange and electrophilic trapping can offer a flexible approach to new 3-substituted AQs starting from an easily available synthetic intermediate. While we decided to oxidize the newly formed boronic acid ester in situ

• , its isolation should be possible and enable further modification, for example by ipso-substitution with heteroatom electrophiles. The application of the boronic acid in Suzuki–Miyaura coupling should also be possible [30][31]. Growth inhibition experiments against S. aureus showed that HQNO

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• -workers [33] demonstrated an efficient route for the construction of the benz[a]anthracene structural unit by employing SM cross coupling followed by RCM sequence. Treatment of the bromonaphthalene derivative 20 with (2-formyl-4-methoxyphenyl)boronic acid (21) in the presence of a palladium catalyst

• respective ring-closure products 62a (98%) and 62b (97%). Finally, SM coupling of 8-halo-7-methoxycoumarins 62a,b with (4-methylfuran-3-yl)boronic acid (63) delivered the cross-coupling product 64 (Scheme 9). In another event, Magnier and co-workers [40] described a simple synthetic route to sulfoximines by

• route to construct the dibenzocyclooctadiene lignan core of the natural product schisandrene via SM coupling and RCM as key steps. In this context, the SM reaction of boronic acid 102 with bromoaldehyde 103 in the presence of Pd2(dba)3 and the S-Phos ligand provided the cross-coupling product 104 (82

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• atmosphere, resulted in a loss of efficiency (Table 1, entry 2). Good results were also observed with phenyl- and 1-naphthylboronic acids (Table 1, entries 5 and 6). Electron-poor arylboronic acids proved to be effective (Table 1, entries 7–10), and only (4-chlorophenyl)boronic acid gave a moderate yield of

• through cross-coupling reactions. Only in the case of two ortho-substituents on the aryl residue of the boronic acid the reaction afforded the target product 10p in low yield (Table 1, entry 17), and 12-unsubstituted derivative 13p as the major product. Then, with the aim of obtaining 12-unsubstituted

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• between 4 with 5 (Table 1). For this purpose we performed a more detailed study of the sequence of coupling with 3,4,5-tribromo-2,6-lutidine. Therefore, a series of Suzuki–Miyaura cross-coupling reactions under different reaction conditions were performed with an amount of boronic acid being

• )-2,6-dimethylpyridine (6) as a substrate in comparison to 3,4,5-tribromo-2,6-dimethylpyridine as substrate. The variation of temperature, reaction time and amount of boronic acid caused only minute changes in the distribution of atropisomers 1–3 with the same almost quantitative total yield (Table 2

• a boronic acid which cannot coordinate the palladium atom and having an electron withdrawing group (for example ortho-chlorophenylboronic acid). We therefore performed a series of reactions of brominated 2,6-lutidine 4 with 9–12 equiv of ortho-chlorophenylboronic acid 11 in different coupling

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• conditions by the Pd-catalyzed Suzuki–Miyaura reaction of the aryldiazonium salts 4a–d with benzo[b]quinolizinium-9-trifluoroborate (3b). The latter substrate was obtained as analytically pure product in moderate yield by the reaction of benzo[b]quinolizinium-9-boronic acid (3a) [34] with NaBF4 (Scheme 1

• acids or esters with base-free conditions are known [39][42], in our hands the reaction of benzo[b]quinolizinium-9-boronic acid (3a) with benzenediazonium tetrafluoroborate 4a only resulted in the formation of the benzo[b]quinolizinium-9-trifluoroborate (3b). Consequently, we used the latter substrate

• -arylbenzo[b]quinolizinium derivatives 1a–d were available in yields that are comparable, or even slightly higher, than the ones obtained with the Suzuki–Miyaura reaction of benzo[b]quinolizinium-9-boronic acid (3a) with bromoarenes [34]. In our previous attempts to synthesize the corresponding benzo[b

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• compatible with both electron-donating and electron-withdrawing substituents on the aryl bromides and boronic acid substrates as well as activated aryl chlorides. Depending on the presence or absence of the TBAB additive, the reaction may be fine-tuned to either proceed via steric or electronic control. The

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