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

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• added 950 μL of a MeOH stock solution, containing 0.5263 M aryl chloride, 0.5525 M boronic acid, 0.5789 M KOt-Bu and 0.2632 M naphthalene. The vial was then heated using an aluminum block heater set to 25 °C. After thermal equilibration, the reaction was initiated via the addition of 50 μL of the

• needle. To the vial was added 950 μL of a MeOH stock solution, containing 0.5263 M aryl chloride, 0.5525 M boronic acid and 0.2632 M naphthalene. The vial was then heated using an aluminum block heater set to 25 °C. After thermal equilibration, the reaction was initiated via the addition of 50 μL of the

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• acidic MeOH (vide infra). There was no reaction in the absence of a proton sourse. No hydroalkylation product at all could be found when alkyl-9-BBN 2a was replaced by (2-phenylethyl)boronic acid pinacolate ester; the substrates hardly reacted at all. A variety of β-disubstituted acrylates were

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• %), LiOH·H2O (4 mmol), 1,4-dioxane (2 mL), water (1 mL), 3.5 h. Syntesis of boronic acid 8b and trifluoroborates 9. Reaction conditions for the synthesis of 8b: 2 (2 mmol), NaIO4 (8 mmol), THF (8 mL), H2O (2 mL), rt, 1 h. Reaction conditions for the synthesis of 9: 2 (2 mmol), KHF2 (10 mmol), MeOH (8 mL), H2O

Synthesis and properties of novel star-shaped oligofluorene conjugated systems with BODIPY cores

• Clara Orofino-Pena,
• Diego Cortizo-Lacalle,
• Joseph Cameron,
• Muhammad T. Sajjad,
• Pavlos P. Manousiadis,
• Neil J. Findlay,
• Alexander L. Kanibolotsky,
• Dimali Amarasinghe,
• Peter J. Skabara,
• Tell Tuttle,
• Graham A. Turnbull and
• Ifor D. W. Samuel

Beilstein J. Org. Chem. 2014, 10, 2704–2714, doi:10.3762/bjoc.10.285

• . Finally, Suzuki coupling of the bromo compound T-B1Br with terfluorenyl boronic acid F3B was achieved in 21% yield. The boronic acid SiFB was synthesised using a previously published procedure [23]. The core precursor T-B0Br was synthesised in 63% yield by using NBS as the brominating reagent instead of

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

• reaction. Formation of trimeric boronic acid anhydride was observed via GC–MS, a species less reactive in arylation reactions. When small amounts of water were added on purpose the reaction solution turned black immediately, most likely due to the formation of Pd black which is inactive in the present

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• -bromophenol using a strategy reported by Diemer et al. [55]. Protection of the hydroxy group to yield 3 [56] was followed by Suzuki cross-coupling with commercial pyridine-4-boronic acid leading to 4. Subsequent deprotection led to 4-(pyridine-4-yl)phenol (5) (Scheme 2) [55]. The preparation of the charge

Clean and fast cross-coupling of aryl halides in one-pot

• Valerica Pandarus,
• Geneviève Gingras,
• François Béland,
• Rosaria Ciriminna and
• Mario Pagliaro

Beilstein J. Org. Chem. 2014, 10, 897–901, doi:10.3762/bjoc.10.87

• emerging as a promising tool for synthetic organic chemistry [9]. In this research context, we have recently described the heterogeneously catalyzed synthesis of boronic acid pinacol esters using a wide range of aryl chlorides, bromides and iodides and bis(pinacolato)diboron as borylating agent over the

• 0.2–0.3 mmol/g palladium loading, a high surface area and large accessible mesoporosity (300–650 m2/g, depending on the applied parameters of the sol–gel synthesis). The leach-proof and truly heterogeneous nature of SiliaCat DPP-Pd in the synthesis of boronic acid pinacol esters has been recently

• intermediate boronic acid pinacol ester. The overall process is described by Scheme 2. The SiliaCat DPP-Pd catalyst mediates the borylation and the subsequent Suzuki–Miyaura reaction in an elegant one-pot sequential synthesis. Hence, an aryl bromide is first converted into the boronic acid pinacol ester (step

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• reported so far [14][15][16][17][18][19][20]. Among the resulting products from the above methods, (R)-(1-amino-3-methylbutyl)boronic acid served as the key mechanism-based pharmacophore in the anticancer drug Velcade, which was the first FDA approved proteasome inhibitor, and has been in clinical use for

• ) and the H-bonds between the molecules (right). Selected bond lengths [Å] and angle [o]: P1–O1 1.505, P1–N1 1.613, N1–H1, 0.957, B1–O2 1.368, the H-bond O1···H2 1.990; the angle of H bond N1–H1···O4 142.79. Previous work for (R)-(1-amino-3-methylbutyl)boronic acid synthesis. Synthesis of (R)-4 and

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• esters [6][7][8][9][10]. Up to now, a series of nucleophilic substrates have been reported to react with α-imino esters, such as enamine [11][12][13][14], carbamate ammonium ylide [15], 1,3-dipolar cycle [16], boronic acid [17], acetylide [18], proparygylic anion [19] and ketene silyl acetal [20]. These

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• . NaOMe reacts with the ligand precursor 26 and forms an N-heterocyclic carbene. The method was tested also with Garner’s aldehyde and two different boronic acid derived nucleophiles (R = Ph or 1-octenyl). High anti-selectivity was observed. With the in situ formed phenyl nucleophile the selectivity was

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

• presence of arylboronic acid (iv and v). The latter evidence prompted the authors to conclude that the aryl group was transferred from the boronic acid and not from the gold complex (i.e. the phenyl group on the in situ formed PPh3AuPh complex acts as a spectator in the process). Based on such observations

• oxygen- and nitrogen-containing coupling partners [83][84]. Interestingly, due to the employment of Selectfluor as a stoichiometric exogenous oxidant, the addition of basic activators for silane reagents were not required. The ready availability of silane precursors, with respect to boronic acid

Consecutive cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate with boronic acids: efficient synthesis of 1,1-diaryl-2,2-difluoroethenes

• Ju Hee Kim,
• Su Jeong Choi and
• In Howa Jeong

Beilstein J. Org. Chem. 2013, 9, 2470–2475, doi:10.3762/bjoc.9.286

• optimized reaction condition was achieved by using Na2CO3 as a base, in which only mono-coupled product 3a was obtained in 92% yield along with the self-coupled product derived from the excess boronic acid. When the reaction was performed in the presence of 5% Pd(PPh3)2Cl2 or Pd(CH3CN)2Cl2 instead of Pd(OAc

• -diaryl-1,1-difluoroethenes. The developed method provides synthetically useful advantages such as a straightforward procedure to give symmetrical and unsymmetrical 2,2-diaryl-1,1-difluoroethenes and the use of a less toxic reagent such as boronic acid. Preparation of 2,2-difluoro-1-iodoethenyl tosylate

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• following one-pot Suzuki–Miyaura/aldol condensation of 134 with boronic acid 135 was carried out at 150 °C in a microwave reactor and gave aristolactam BII (115) in good yield. By variation of the coupling partners, Heo was able to efficiently synthesize a library of natural and non-natural analogues

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• to C14–C15 of ripostatin A instead was sought. Oxy-Michael approach to epoxide We were intrigued by a recent report by Falck describing an organocatalytic oxy-Michael addition to achiral δ-hydroxy-α,β-enones (Scheme 12) [52]. The hydroxy group is delivered in a directed fashion from the boronic acid

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• ]. It involves several steps: transmetallation of boronic acid with a catalyst, coordination of the azole molecule to the Cu(II) species followed by oxidation of copper(II) into copper(III) in the presence of oxygen, and then reductive elimination releasing the product and Cu(I) complex. A regeneration

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• tert-butyl carbamates 5 prior to undergoing palladium-mediated Suzuki reactions with various boronic acid partners. Under the reaction conditions, the carbamate-protecting group was also cleaved to afford the desired 3-arylindazoles, albeit as the unprotected systems 6. Alkylation with methyl

Conformational analysis and intramolecular interactions in monosubstituted phenylboranes and phenylboronic acids

• Josué M. Silla,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2013, 9, 1127–1134, doi:10.3762/bjoc.9.125

• ; monosubstituted phenylboranes; phenylboronic acids; Introduction Boronic acid derivatives have been widely studied because of their good performance as pharmaceutical agents, serving in the development of enzyme inhibitors of peptidases/proteases, proteasomes, arginase, nitric oxide synthase (NOS), and

• transpeptidases [1][2]. Other important studies incorporate the boronic acid moiety into amino acids and nucleosides as antitumor and antiviral agents [3][4]. Indeed, the great importance of aromatic boronic acids to biological and pharmaceutical purposes has been reported, as well as the interest to introduce a

• boronic acid moiety in organic molecules [5]. Boron has been shown to bind with nitrogen in order to form a ring in 2-(N,N-dimethylaminomethyl)phenylboronic acid [6], thus reflecting its electron acceptor ability through intramolecular interactions. In addition, computational studies have been performed

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• catalyzed Suzuki coupling of the starting halide 73 and boronic acid 74 followed by N-methylation of 75 with [3H]methyl iodide and O-demethylation with sodium thiophenoxide (Scheme 6C). Compound 57 showed high affinity for Aβ1-40 fibrils in vitro (Kd = 8.4 nM) and lower background binding levels than 56c

• binding in vivo. Several [18F]-labeled benzofurans have been employed with success for Aβ imaging. [18F]FPYBF-1 (123a), which has a N,N-dimethyl-2-aminopyridine group attached to the benzofuran core, was synthesized via Suzuki coupling between 5-methoxybenzofuran-2-boronic acid (130) and 2-amino-5

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• -benzyl formation also promoted the desired coupling, albeit in lower yield over the time frame allowed (12 h, Table 2, entry 7). With the optimal conditions in hand, we next tested the scope of the reaction using various boronic acid and coumarinyl acetates (Scheme 3). Regarding the boronic acid coupling