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

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• calculated as if complete conversion had taken place. GP 3 - Suzuki reaction: Under an argon atmosphere, one equiv of the respective 7-bromo-1H-indole-6-carboxymethyl-polystyrene is suspended in DMF (0.1 mmol/mL) together with 0.10 equiv of tetrakis(triphenylphosphine)palladium and two equiv of boronic acid

Synthesis of new pyrrole–pyridine-based ligands using an in situ Suzuki coupling method

• Matthias Böttger,
• Björn Wiegmann,
• Steffen Schaumburg,
• Peter G. Jones,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2012, 8, 1037–1047, doi:10.3762/bjoc.8.116

• the synthesis of the new structures 1–3. Results and Discussion Our first retrosynthetic approach included a Suzuki coupling of the alpha-substituted boronic acid of Boc-protected pyrrole 7 with the heteroaryl bromides 8–10, as shown in Scheme 3. Compound 7 is described in literature [10], but it

• could not be purified by column chromatography and therefore was not isolated as a pure product. In addition, reports on the stability of this boronic acid show that it is not suitable for long-term storage [10]. We therefore applied a modification of the Suzuki coupling that was also used to prepare

• [2.2]paracyclophane-derivatives [11]. This comprised the in situ reaction of the freshly prepared boronic acid/ester with the heteroaryl bromides 8–10. These starting compounds could be prepared by using literature procedures, as shown in Scheme 4. Substance 8 was synthesized by following the standard

On the bromination of the dihydroazulene/vinylheptafulvene photo-/thermoswitch

• Virginia Mazzanti,
• Martina Cacciarini,
• Søren L. Broman,
• Christian R. Parker,
• Magnus Schau-Magnussen,
• Andrew D. Bond and
• Mogens B. Nielsen

Beilstein J. Org. Chem. 2012, 8, 958–966, doi:10.3762/bjoc.8.108

• structure analysis (Figure 3d). Moreover, a Suzuki cross-coupling reaction with boronic acid 16 gave the product 17, albeit in rather low yield (Scheme 7). The substitution was confirmed by NOESY 1D experiments (see Supporting Information File 1). Finally, we observed that upon storage at room temperature

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• transesterification reaction were screened. Boronic acid [91] and indium(III) iodide [92] yielded no transesterification product with propargyl alcohol, while Ti(OiPr)4 [93] gave only a trace of the desired product, with mostly detosylation resulting. Otera’s catalyst [94] proved to be optimal, giving cycloaddition

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• dipolarophiles to yield aryl isoxazolines with the boronate ester function intact and available for subsequent reaction. Keywords: dipolar cycloaddition; heterocycle; nitrile oxide; hypervalent iodine oxidation; pinacol boronic acid esters; Introduction Metal-mediated coupling reactions to form carbon–carbon

• favouring the oxidation of carbon–boron bonds, which makes boronic ester chemistry chemoselective, is a constraint that potentially limits the utility of nitrile oxide cycloadditions in the presence of a boronic acid ester. 4-Formylphenylboronic acid pinacol ester 4 is commercially available or easily

• prepared from the corresponding boronic acid, via the bromide [33]. Reaction with 50% aqueous hydroxylamine gives the aldoxime 5 in good yield (Scheme 3). Only one geometric isomer of the aldoxime was observed in the 1H and 13C NMR spectra, and this was assigned as the Z isomer based on the 8.17 ppm

Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

• Mohamed Abboud,
• Emmanuel Aubert and
• Victor Mamane

Beilstein J. Org. Chem. 2012, 8, 253–258, doi:10.3762/bjoc.8.26

• ] of 3a with boronic acid 4 was less efficient giving only the mono-functionalized compound 10 in 42% yield (Scheme 3) while no conversion was observed with 4-methylthiobenzene boronic acid. Better results were obtained by means of a reverse sequence. First, the C-2- and C-2’-positions of bipyridine 2b

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• THF at 0 °C and cannulation of the resulting mixture into a solution of trimethyl borate in THF afforded boronic acid 44 (Scheme 9) in 90% yield after the customary aqueous workup [87]. This material underwent smooth Suzuki coupling with the known 45 [81][82][83], and the action of aqueous NBS [88

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• species with a boronic acid or triethylborane, followed by a reductive elimination, afforded the indenamine core in good to excellent yields. However, this Pd-catalyzed cyclization was only effective for aldehydes since ketones did not participate in the process (Scheme 6). Tsukamato extended this

• the Pd(II) complex and a boronic acid activated by CsF, followed by insertion of the resulting σ-arylpalladium(II) into the allenic moiety leading to a π-allyl intermediate. This can undergo a nucleophilic allyl transfer to the imine, generating an amino-Pd(II) complex, which can subsequently add to

• another allenic unit. After a new transmetalation step with the boronic acid, the active catalytic species can be released and entered into a new catalytic cycle (Scheme 13). Imine as a nucleophilic partner A tandem four-component reaction allowing access to 1,2-dihydroisoquinolin-1-ylphosphonates 26 was

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• moderate chemoselectivity of organozinc reagents towards substrates bearing acidic hydrogen atoms, such as N–H and O–H bonds. This is an important limitation of the Negishi cross-coupling, especially compared to the Suzuki cross-coupling based on boronic acid derivatives, which are much more tolerant

Au(I)/Au(III)-catalyzed Sonogashira-type reactions of functionalized terminal alkynes with arylboronic acids under mild conditions

• Deyun Qian and
• Junliang Zhang

Beilstein J. Org. Chem. 2011, 7, 808–812, doi:10.3762/bjoc.7.92

• hand, the more electron-rich 4-methoxyphenylboronic acid produced the lowest yield, likely due to a competing oxidation of the boronic acid by Selectfluor® [27][30]. Gratifyingly, a number of potentially reactive functionalities, such as tertiary amine, 4-methylbenzenesulfonate, 1,6-enyne and 1,6-diyne

Stereogenic boron in 2-amino-1,1-diphenylethanol-based boronate–imine and amine complexes

• Sebastian Schlecht,
• Walter Frank and
• Manfred Braun

Beilstein J. Org. Chem. 2011, 7, 615–621, doi:10.3762/bjoc.7.72

• combined organic layers were dried with sodium sulfate and the solvent was removed in a rotary evaporator. Immediately, the resulting crude colorless product, 4-chlorophenyl boronic acid (0.122 g, 1.00 mmol) and sodium hydrogen carbonate (0.13 g, 1.5 mmol) were suspended in 100 mL of dry toluene and heated

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• reflux condenser, were added the aryl halide (1 mmol), boronic acid (1.25 mmol), Na2CO3 (2 mmol), and Pd/NiFe2O4 (0.1 mol %) in 4 mL DMF/H2O (1:1), and the reaction mixture heated at the appropriate temperature and duration. The reaction was monitored by gas chromatography. After the reaction was

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis. Keywords: biologically active compounds; boronic acid; copper; N-arylation; palladium; Introduction Palladium- and

• boronic acid 107, p-methyl and m-fluoro substituents were also tolerated. The xanthine compounds showed good anti-proliferative activity and exhibited a significant fluorescence response [76]. The peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor superfamily, are

• boronic acid have to be used. Boronic acid reagents can have electron-donating and electron-withdrawing substituents in ortho-, meta- and para-positions, but boronic acids with sterically demanding substituents were found to be unreactive. Many precursors for the starting materials used in Chan–Lam

Syntheses and properties of thienyl-substituted dithienophenazines

• Annemarie Meyer,
• Eva Sigmund,
• Friedhelm Luppertz,
• Gregor Schnakenburg,
• Immanuel Gadaczek,
• Thomas Bredow,
• Stefan-S. Jester and
• Sigurd Höger

Beilstein J. Org. Chem. 2010, 6, 1180–1187, doi:10.3762/bjoc.6.135

• quantitative yield [21][22]. The respective regio isomer 8 was synthesized starting from commercially available 3-bromothiophene 1 and boronic acid 5 in three steps (Scheme 2). By Suzuki–Miyaura coupling we obtained 3,3’-bithiophene in good yields. The red diketone 7 was prepared by two-fold acylation with

A perfluorocyclopentene based diarylethene bearing two terpyridine moieties – synthesis, photochemical properties and influence of transition metal ions

• Falk Wehmeier and
• Jochen Mattay

Beilstein J. Org. Chem. 2010, 6, No. 53, doi:10.3762/bjoc.6.53

• routes to terpyridine substituted diarylethenes via the above mentioned catalytic cross coupling reactions require suitably functionalized terpyridine precursors, e.g. boronic acid derivatives for Suzuki type cross coupling reactions. 4′-(4-Bromophenyl)-2,2′:6′,2″-terpyridine (7a) and its meta

• -substituted analogue 7b can be synthesized by Kröhnke-condensation of 2-acetylpyridine (5) with p-bromobenzaldehyde (6a) or m-bromobenzaldehyde (6b), respectively [15]. Miyaura type cross coupling reactions of 7a and 7b with 5,5,5′,5′-tetramethyl-2,2′-di(1,3,2-dioxaborinan) (8) led to the formation of boronic

• acid derivatives 9a [16] and 9b (Scheme 2). The terpyridine moieties can be attached to the diarylethene unit by Suzuki type cross coupling of the diiodo switch 4 with the boronic esters 9a and 9b under conditions similar to those described for other aryl boronic acids and their derivatives to yield

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32