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

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• (Neu5Hex, 3) was achieved by a previously described route [9]. The Petasis coupling was performed starting from D-arabinose (4), the secondary amine 5 and dibutyl vinyl boronic acid ester 6. In situ hydrolysis of the bis(4-methoxyphenyl)methyl group with a catalytic amount of trifluoroacetic acid (TFA

• -tetrahydroxy-1-vinyl-pentyl)-amide (8) A solution of D-arabinose (1.09 g, 5.73 mmol, 4), 4,4’-dimethoxybenzhydrylamine (1.39 g, 5.73 mmol, 5) and vinyl boronic acid dibutyl ester (2.51 g, 11.46 mmol, 6) in aqueous ethanol (60 mL, ethanol/H2O = 4:1) was stirred at 50 °C for 72 h. TFA (1.79 ml) was added and the

Solvent-free and time-efficient Suzuki–Miyaura reaction in a ball mill: the solid reagent system KF–Al₂O₃ under inspection

• Franziska Bernhardt,
• Ronald Trotzki,
• Tony Szuppa,
• Achim Stolle and
• Bernd Ondruschka

Beilstein J. Org. Chem. 2010, 6, No. 7, doi:10.3762/bjoc.6.7

• situ activation, which enhances the capability of aluminas to act as a base in Suzuki–Miyaura reactions probably because of the generation of new highly active surfaces [59] including the defect sites that allow the activation of the boronic acid as mentioned above. Besides the intriguing fact that

• that basic alumina yields the best results, whereas neutral alumina is inactive [35]. The authors assumed that alumina with basic surface characteristics allows the in situ formation of “interfacial” boronic esters resulting from the electronic interaction between electron-deficient boron in boronic

• acid and surface oxygen of alumina (ArB(OH)2–O–Al(O–)3). The reported results also confute the results from microwave-assisted cross-coupling with pure basic alumina, which was seen to be completely inert for this type of reaction [33]. Apparently co-grinding of all reactants in a ball mill leads to in

Ring-alkyl connecting group effect on mesogenic properties of p-carborane derivatives and their hydrocarbon analogues

• Aleksandra Jankowiak,
• Piotr Kaszynski,
• William R. Tilford,
• Kiminori Ohta,
• Adam Januszko,
• Takashi Nagamine and
• Yasuyuki Endo

Beilstein J. Org. Chem. 2009, 5, No. 83, doi:10.3762/bjoc.5.83

• % yield from 1,4-dibromobenzene and (4-methoxyphenyl)boronic acid using the Suzuki coupling procedure [29]. This method is comparable to other Pd(0)-assisted methods for the synthesis of 14D[0] [30][31][32]. The 10-vertex p-carborane diester 18B was obtained from the corresponding dicarboxylic acid 22B

Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

• Andreas Speicher,
• Timo Backes,
• Kerstin Hesidens and
• Jürgen Kolz

Beilstein J. Org. Chem. 2009, 5, No. 71, doi:10.3762/bjoc.5.71

• the syntheses of 3/4) should give rise only to the Z geometry at the a–d stilbene bridge. The a–b part 14 [15] of the target molecules was prepared by Suzuki coupling of the boronic acid 12 with its precursor 11, readily available from 3-bromo-4-methoxybenzaldehyde (10) [21] by an improved procedure

• benzylic alcohol 20 [28]. Protection as the THP acetal 21 was essential before preparing the boronic acid 22. Previously (see [15]), we reported on a synthesis of 22 starting with the bromination of 3-methoxybenzyl alcohol to 4-bromo-3-methoxybenzyl alcohol. In contrast to the original contribution [29

• boronic acid 22 with the bromoarene 16 under carefully optimized conditions followed by acidic workup afforded the hydroxyaldehyde 27 as precursor for cyclization (Scheme 6). A cyclization protocol for the intramolecular Wittig reaction, well established [15][20] for the synthesis of the tetramethyl ether

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• . Unfortunately, under identical conditions no cross-coupled products were obtained following several attempts using Z-crotyl boronic acid and vinyl boronic acid. Hydrogenation of the trisubstituted alkene in compounds 27–30 was carried out in DMF due to the poor solubility of these compounds in more standard

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• the initial reaction with the boronic acid (Scheme 1). On the other hand, triarylboroxins, easily prepared from the corresponding arylboronic acids by thermally induced dehydration under vacuum, have recently been applied with success as the starting materials for the preparation of the ArZnEt species

• ) and its polystyrene-immobilized analogue 2. Experimental set-up for the continuous flow experiments. (A) Schematic representation and (B) Actual system. Generation of the mixed ArZnEt species from a boronic acid and Et2Zn. Generation of the mixed ArZnEt species from a triarylboroxin and Et2Zn

Studies on polynuclear furoquinones. Part 1: Synthesis of tri- and tetra- cyclic furoquinones simulating BCD/ABCD ring system of furoquinone diterpenoids

• Faruk H. Shaik and
• Gandhi K. Kar

Beilstein J. Org. Chem. 2009, 5, No. 47, doi:10.3762/bjoc.5.47

• 2-bromo-3,4-dihydro-1-naphthaldehyde. The bromoaldehyde was converted to methyl 2-(2-bromo-1-naphthyl)acetate or 2-(2-bromo-1-naphthyl)acetonitrile following the protocol of functional group transformations. Subsequent Suzuki coupling of this ester/nitrile derivative with furan-2-boronic acid

• -bromo-3,4-dihydro-1-naphthaldehyde 1 [34] was utilized as A, B ring precursor and commercially available furan 2-boronic acid as D-ring precursor. In the event of the synthesis, the C ring was constructed to reach the target molecule in 8-10 steps. The key steps in our synthesis deal with the formation

• -naphthaldehyde (a substrate easily available by Vilsmeier–Haack reaction on 2-tetralone) and furan-2-boronic acid (a commercially available material) (Figure 3). When 2-bromo-3,4-dihydro-1-naphthaldehyde (easily obtained in 68% yield by the reaction of 2-tetralone and PBr3/DMF in CHCl3 at room temperature) was

Preparation and Diels–Alder/cross coupling reactions of a 2-diethanolaminoboron- substituted 1,3-diene

• Liqiong Wang,
• Cynthia S. Day,
• Marcus W. Wright and
• Mark E. Welker

Beilstein J. Org. Chem. 2009, 5, No. 45, doi:10.3762/bjoc.5.45

• , 0.5 M HCl solution (100 mL) was added. The reaction mixture was extracted with Et2O (2 × 75 mL). The combined colorless clear organic layers were dried over MgSO4, and the volatiles were removed by a rotary evaporator (30 °C, 20 Torr) to yield the dieneboronic acid. The boronic acid was added at once

Regioselective alkynylation followed by Suzuki coupling of 2,4-dichloroquinoline: Synthesis of 2-alkynyl- 4-arylquinolines

• Ellanki A. Reddy,
• Aminul Islam,
• K. Mukkanti,
• Venkanna Bandameedi,
• Dipal R. Bhowmik and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 32, doi:10.3762/bjoc.5.32

• ) 10.3762/bjoc.5.32 Abstract A two step synthesis of 2-alkynyl-4-arylquinolines has been accomplished via Pd/C-mediated regioselective C-2 alkynylation of 2,4-dichloroquinoline in water followed by Suzuki coupling at C-4 of the resulting 4-chloro derivative. Keywords: alkyne; boronic acid; catalysis; 2,4

• ), 3-methoxyphenylboronic acid (entry 7, Table 2) and 4-fluorophenyl boronic acid (entry 8, Table 2), all of which participated well in the coupling reaction with 3. A number of 2-alkynyl-4-arylquinolines (5) were prepared in good to excellent yields without affecting the alkynyl substituents present

Convenient methods for preparing π-conjugated linkers as building blocks for modular chemistry

• Jiří Kulhánek,
• Filip Bureš and
• Miroslav Ludwig

Beilstein J. Org. Chem. 2009, 5, No. 11, doi:10.3762/bjoc.5.11

• use as building blocks in Suzuki–Miyaura or Sonogashira coupling reactions. Keywords: boronic acid; donor/acceptor; linker; Sonogashira reaction; property tuning; push-pull; Suzuki–Miyaura reaction; Introduction Development of new organic compounds with improved and advanced properties is one of the

• triisopropyl borate followed by esterification with pinacol afforded dioxaborolanes 4b–c in the yields of 81 and 83% (Scheme 1, Method B). The biphenyl-4-boronic acid corresponding to 4a was also commercially available while 4b was reported as a side product [35] without full characterization. Whereas 5a was

Catalytic synthesis of (E)-α,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene

• Rubén Manzano,
• Lidia Ozores,
• Andreas Job,
• Lars Rodefeld and
• Benjamin List

Beilstein J. Org. Chem. 2009, 5, No. 3, doi:10.3762/bjoc.5.3

• leads to the formation of water and CO2 as the only by-products (Scheme 1, eq 3) [23][24]. Here we describe as a new approach, the boronic acid-catalyzed condensation of ketene dialkyl acetal with aldehydes to furnish α,β-unsaturated esters in good yields and reliably high (E)-stereoselectivities

• this particular boronic acid, which possesses both Lewis acidity and Brønsted acidity, was the most active catalyst and gave the highest yields of the corresponding α,β-unsaturated ester. The optimized procedure involved the slow addition of 1,1-diethoxyethylene to benzaldehyde in the presence of a

• mechanism that explains the peculiar effectiveness of boronic acids as catalysts (Scheme 2). Accordingly, the boronic acid functions as a Lewis acid activating the aldehyde but also as a hydroxide donor facilitating the departure of ethanol from an activated intermediate. Clearly, alternative mechanisms may

N-Arylation of amines, amides, imides and sulfonamides with arylboroxines catalyzed by simple copper salt/EtOH system

• Zhang-Guo Zheng,
• Jun Wen,
• Na Wang,
• Bo Wu and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2008, 4, No. 40, doi:10.3762/bjoc.4.40

• recently in the mechanism of the cross-coupling reaction based on boronic acid. The group of Chan has reported the dynamic behavior of boronic acid in the copper salt catalytic system. The results implied that the active arylating agent such as arylboronic acid in the cross-coupling reaction is indeed its

A convenient catalyst system for microwave accelerated cross- coupling of a range of aryl boronic acids with aryl chlorides

• Matthew L. Clarke,
• Marcia B. France,
• Jose A. Fuentes,
• Edward J. Milton and
• Geoffrey J. Roff

Beilstein J. Org. Chem. 2007, 3, No. 18, doi:10.1186/1860-5397-3-18

• -phenyl boronic acid and 4-formyl boronic acid was investigated, since products 3 and 4 are potential intermediates in the synthesis of the clinically used drugs, Losartan and Valsartan respectively. [28][29] Under conventional heating conditions, attempts to couple 4-formyl benzene boronic acid to 2

• -chloro-benzonitrile, under conditions that gave high yields using phenyl boronic acid, gave essentially no product (<5% as determined by NMR, GC and TLC analysis). However, reactions carried out in the microwave gave good isolated yields after just 15 minutes at 140°C in acetonitrile. This reason for

• this difference in reactivity is not clear. However, a number of observations made during our studies suggested that the nature of the boronic acid nucleophile can have a major effect on the productivity of cross-coupling reactions. The majority of studies, including our own, have neglected to fully