Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira–Glaser cyclization sequence

• Dominik Urselmann,
• Dragutin Antovic and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1499–1503, doi:10.3762/bjoc.7.174

• Dominik Urselmann Dragutin Antovic Thomas J. J. Muller Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.7.174 Abstract Based upon a consecutive one-pot Sonogashira–Glaser coupling

• efficiency is also variable. Just recently we reported a very straightforward one-pot synthesis of symmetric 1,4-di(hetero)arylated 1,3-butadiynes starting from (hetero)aryl iodides by virtue of a sequentially Pd/Cu-catalyzed [14] Sonogashira–Glaser process (Scheme 1) [15]. According to this general one-pot

• Sonogashira–Glaser cyclization sequence. Results and Discussion The conversion of 1,4-diaryl-1,3-butadiynes into 2,5-diarylthiophenes by base-mediated cyclization with sodium sulfide or sodium hydrogen sulfide is a literature-known procedure [16][17][18][19][20][21][22][23]. Therefore, we reasoned that the

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

• reported by Wu and coworkers. Initial Sonogashira coupling was effected between a 2-bromobenzaldehyde and an alkyne in the presence of catalytic amounts of PdCl2(PPh3)2 and CuI. After complete conversion of the aldehyde into the coupling product 25 (TLC control), a primary amine and diethylphosphite were

• ,β-unsaturated ketones generated in situ by Pd-catalyzed Sonogashira cross-coupling reactions. For instance, by building on their expertise in this area [14] Müller and coworkers recently developed a very effective and modular three-component strategy to assemble a series of 3,5-bis(hetero)aromatic

• are formed, they immediately react with hydrazine to form pyrazole by a specific rate acceleration in the one-pot process [16]. The Sonogashira cross-coupling of acid chlorides with terminal alkynes has also been demonstrated as a valuable tool to generate, in situ, ynones bearing a pendant amine

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• benzo[b]furan derivatives has been developed from 3-halo-2-iodoanisoles bearing an additional methoxy group, which have been accessed through an ortho-zincation/iodination reaction. Two palladium-catalyzed processes, namely a Sonogashira coupling followed by a tandem hydroxylation/cyclization sequence

• ring system, the cyclodehydration of α-aryloxy ketones [29], the Claisen rearrangement of an allyl aryl ether followed by Pd-catalyzed intramolecular oxidative cyclization [30], and the tandem Sonogashira coupling/heterocyclization of 2-halophenols with terminal alkynes [31], are some of the most used

• Sonogashira coupling and a tandem hydroxylation/heterocyclization reaction. The required o-dihaloanisole derivatives could be prepared by a selective ortho-metallation reaction and subsequent electrophilic quenching with iodine (Scheme 1). Results and Discussion As established in our proposed retrosynthetic

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• one-pot four-component syntheses toward pyrimidyl- and pyrazolylazulenes. Results and Discussion Recently, we reported a three-component synthesis leading to the formation of ynones by a conceptually novel glyoxylation–decarbonylative Sonogashira coupling sequence (Scheme 2) [47]. The Lewis acid free

• glyoxylation of electron rich N-heterocycles, such as indoles and pyrroles, leads to the formation of glyoxylyl chlorides, which can be reacted without isolation by decarbonylative Sonogashira coupling to form the desired ynones. So far, only one example of the synthesis of azulenylynones has been described

• monitoring by TLC, glyoxylation of guaiazulene (1b) was incomplete even after 24 h reaction time (Table 1, entry 3). Shorter reaction times in the first step caused a substantial decrease of the yield (Table 1, entry 4), whereas longer reaction times in the Sonogashira coupling had no effect on the yield

Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene

• Alexandre Pradal,
• Chung-Meng Chao,
• Patrick Y. Toullec and
• Véronique Michelet

Beilstein J. Org. Chem. 2011, 7, 1021–1029, doi:10.3762/bjoc.7.116

• studies. Synthesis of 1,6-enynes We prepared various oxygen-tethered 1,6-enynes according to classic methodologies employing a Williamson alkylation reaction and/or a Sonogashira cross-coupling [60][61] (Scheme 2 and Scheme 3). The known enyne 5 [62][63] was engaged in Pd-catalyzed coupling in the

• yield. We also envisaged preparing two trisubstituted alkenes 2g and 2h by an alkylation/Sonogashira sequence starting from commercially available substrates 7 and 8. We also selected some nitrogen-tethered 1,6-enynes 1b–e from the literature [23][41][42][43][44] and synthesized them to evaluate the

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• nonaflates are excellent coupling partners in palladium-catalyzed transformations such as Suzuki, Stille, Heck and Sonogashira reactions [45]. However, in contrast to the smooth nonaflation, the selective O-alkylation of the synthesized pyridines turned out to be more challenging (Scheme 5). Whereas pyridone

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• carbon–carbon bond coupling reactions have been less explored [88][89]. In 2008, Li et al. reported a gold(I) iodide catalyzed Sonogashira reaction [88]. Terminal alkynes 197 reacted smoothly with aryl iodides and bromides 198 in the presence of 1 mol % AuI and 1 mol % dppf to generate the corresponding

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• stabilising B. The substrates were prepared by Sonogashira reaction between propargyl alcohol and the appropriately substituted iodobenzene substrate 22, 23 (Scheme 12). Functional group interconversion of the alcohols by bromination and substitution results in the sulfonium salts 28, 29 which were reacted

Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates

• Wang-Yong Yang,
• Samantha A. Marrone,
• Nalisha Minors,
• Diego A. R. Zorio and
• Igor V. Alabugin

Beilstein J. Org. Chem. 2011, 7, 813–823, doi:10.3762/bjoc.7.93

• corresponding lysine conjugates shown in Figure 4. Results and Discussion Synthesis The regioisomeric diaryl alkynes were synthesized following the synthetic strategy previously outlined by us for compound 1 [25]. The Sonogashira coupling of the corresponding iodonitrobenzene with trimethylsilyl (TMS) acetylene

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

• , Chinese Academy of Sciences, Ling Ling Road 345 Shanghai 200032 (P. R. China) 10.3762/bjoc.7.92 Abstract A straightforward, efficient, and reliable redox catalyst system for the Au(I)/Au(III)-catalyzed Sonogashira cross-coupling reaction of functionalized terminal alkynes with arylboronic acids under

• mild conditions has been developed. Keywords: arylboronic acid; gold-catalysis; Sonogashira cross-coupling; Introduction The Sonogashira reaction has become the most important and widely used method for the synthesis of arylalkynes and conjugated enynes, which are precursors for natural products

• , pharmaceuticals and other materials [1][2][3]. In the past decade, considerable efforts have been made to enhance the efficiency and generality of this reaction. All kinds of palladium catalyst systems [4][5][6][7][8][9][10] and other metal catalyst systems [3] have been developed for facilitating the Sonogashira

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• access to 3-silylalkynyl indoles. To the best of our knowledge, this is the first example of a one-pot process combining a Au(III) and a Au(I) catalyst. Findings 2-Alkynylanilines 2 can be efficiently prepared from 2-iodoanilines 4 and terminal alkynes via Sonogashira reaction with Et3N as solvent

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• -naphthyl derivatives. Construction of a new 1-naphthyl ring as an essential step toward 1,1'-binaphthyls is rare [17][18][19]. Results and Discussion The Sonogashira reaction between 1-ethynyl-2-methoxybenzene (4a) and 1-iodo-2-[2-(trimethylsilyl)ethynyl]benzene produced 5a, which was desilylated to give

A rapid and efficient synthetic route to terminal arylacetylenes by tetrabutylammonium hydroxide- and methanol-catalyzed cleavage of 4-aryl-2-methyl-3-butyn-2-ols

• Jie Li and
• Pengcheng Huang

Beilstein J. Org. Chem. 2011, 7, 426–431, doi:10.3762/bjoc.7.55

• have been widely used in the preparation of photoelectric devices such as organic light-emitting diodes (OLEDs) [1][2][3][4], field-effect transistors (OFETs) [5][6], and organic photovoltaic cells (OPVCs) [7][8][9]. The palladium-catalyzed Sonogashira cross-coupling of an aryl halide with a mono

C–C (alkynylation) vs C–O (ether) bond formation under Pd/C–Cu catalysis: synthesis and pharmacological evaluation of 4-alkynylthieno[2,3-d]pyrimidines

• Dhilli Rao Gorja,
• K. Shiva Kumar,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2011, 7, 338–345, doi:10.3762/bjoc.7.44

• ]pyrimidines C (Figure 1). These derivatives are attractive due to the synthetic potential of C-4 alkynyl fragments for further use in library construction. A number of methods have been reported for the synthesis of alkynyl substituted pyrimidines and most of which involve the use of Sonogashira coupling of

• halopyrimidines with terminal alkynes [1][2][3] (for a review see [8]). While alkynylation of the thiophene ring of thienopyrimidines under Sonogashira conditions [9] has previously been reported [6], a similar coupling reaction on the pyrimidine ring of thieno[2,3-d]pyrimidines is uncommon in the literature [10

• ]. The use of Pd/C–CuI–PPh3 as a less expensive catalyst system for efficient Sonogashira coupling has been explored earlier. Due to our continuing interest in Pd/C-mediated alkynylation of aryl and heteroaryl halides we decided to investigate the Pd/C-based methodology for the synthesis of our target

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• construction of the benzofuran moiety from intermediate 5. For the construction of 2-substituted benzofurans, the most widely used approach involves the palladium-catalyzed heteroannulation of 2-halophenols with a terminal alkyne via a tandem Sonogashira coupling-5-endo-dig-cyclization, largely based on the

Donor-acceptor substituted phenylethynyltriphenylenes – excited state intramolecular charge transfer, solvatochromic absorption and fluorescence emission

• Ritesh Nandy and
• Sethuraman Sankararaman

Beilstein J. Org. Chem. 2010, 6, 992–1001, doi:10.3762/bjoc.6.112

• (2) with 1,1-dimethylpropargyl alcohol followed by deprotection with KOH in refluxing toluene (Scheme 2). 2-Phenylethynyltriphenylene (1a) and those bearing electron withdrawing substituent (1b–e) were synthesized by the Sonogashira coupling of 2-iodotriphenylene (2) with the corresponding

• phenylacetylene derivatives. Although 1f–g were also synthesized by this procedure, their purification proved difficult due to an inseparable minor product formed in these reactions. Therefore compounds 1f–g were synthesized via the Sonogashira coupling of 2-ethynyltriphenylene (4) and the corresponding

Conjugated polymers containing diketopyrrolopyrrole units in the main chain

• Bernd Tieke,
• A. Raman Rabindranath,
• Kai Zhang and
• Yu Zhu

Beilstein J. Org. Chem. 2010, 6, 830–845, doi:10.3762/bjoc.6.92

• polycondensation reactions such as Suzuki [17], Stille [18] and Heck [19] coupling are especially useful. Other suitable reactions are Ni-mediated Yamamoto coupling [20], Sonogashira coupling [21], or electrochemical polymerization [22]. In the following, a brief review of recently prepared DPP based polymers is

• -sensitized solar cells were fabricated with P-12 as active layer. A power conversion efficiency of 1.43% was reached. G. Zhang et al. [52] synthesized diphenylDPP-containing polyphenylene-vinylene (PPV)- and polyphenylene-ethynylene (PPE)-type conjugated polymers via Heck- and Sonogashira coupling

• Suzuki coupling and their characteristic properties. List of DPP-polymers prepared upon Stille, Heck and Sonogashira coupling and their characteristic properties. List of DPP-based polyiminoarylenes and their characteristic properties [37]. List of DPP-polymers prepared upon electrochemical

One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes

• Priyabrata Roy and
• Binay Krishna Ghorai

Beilstein J. Org. Chem. 2010, 6, No. 52, doi:10.3762/bjoc.6.52

• ] using palladium catalyzed Sonogashira coupling reactions as depicted in Scheme 2. Iodoketone 6A was prepared in 80% yield from (3-chloro-2-pyrazinyl)phenylmethanone [35] by halogen exchange with NaI in acetonitrile. The three component coupling reaction of pyrazinyl ketone 1A, carbene complex 2 and N

Preparation of pyridine-3,4-diols, their crystal packing and their use as precursors for palladium-catalyzed cross-coupling reactions

• Tilman Lechel,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 42, doi:10.3762/bjoc.6.42

• possible palladium-catalyzed cross-couplings we performed several Sonogashira-reactions [28][29][30]. As described in Scheme 3, the pyridinyl-bistriflates or -nonaflates 3 were coupled with alkynes like phenylacetylene or (triisopropylsilyl)acetylene using Pd(PPh3)4 or alternatively, Pd(OAc)2/PPh3 as

• (C-H), 1600–1575 (C=C) cm−1. C12H10F9NO6S2 (499.3): calcd. C, 28.86; H, 2.02; N, 2.81; found: C, 28.89; H, 1.68; N 2.87. Sonogashira coupling reaction, typical procedure A mixture of pyridinediyl bistriflate 3b (245 mg, 0.491 mmol), Pd(PPh3)4 (79 mg, 0.069 mmol), CuI (9.4 mg, 0.049 mmol

• of 3-alkoxypyridinols 1 to pyridine-3,4-diols 2. aMethod a: Pd/C, H2, MeOH, rt, 1 d; bMethod b: BBr3, CH2Cl2, 0 °C to rt, 1 d; cMethod c: TFA:CH2Cl2 (1:2), rt, 1 h. Conversion of pyridine-3,4-diols 2 into pyridinediyl bistriflates or -nonaflates 3. a) Et3N, Rf2O, CH2Cl2, 0 °C to rt, 1 d. Sonogashira

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

• comminuting the reactants for just 10 min [40][41] without the presence of any additional stabilizing or activating ligands. Compared to the original published procedure for the Suzuki–Miyaura reaction [36] or the protocols featured by Mack and Frejd and their coworkers for Sonogashira [54] and Heck–Jeffery

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

• report on the total synthesis of compounds which possess more rigid two-carbon biaryl bridges like stilbene (E or Z) or even tolane moieties which were introduced starting with a Sonogashira protocol. The McMurry method proved to be a powerful tool for the cyclization to these considerably ring-strained

• adopted because they do not give rise to specific double bond geometry or even an alkyne moiety between rings b and c. Our new strategy of synthesis involved a consecutive coupling of the rings a-b-c-d whereby the two-carbon bridge b–c would be introduced by a Sonogashira type reaction yielding an alkyne

• [22]. The aldehyde 13 was transformed into the terminal alkyne 14 by chain extension [23] (Scheme 3). The coupling of the terminal alkyne 14 with the iodoarene 15 [24] as the “c” building block using a typical Sonogashira protocol [Pd(PPh3)4, CuI, Et3N] gave – even under an argon–hydrogen atmosphere

Pd/C-mediated synthesis of α-pyrone fused with a five-membered nitrogen heteroaryl ring: A new route to pyrano[4,3-c]pyrazol-4(1H)-ones

• Dhilli Rao Gorja,
• Venkateswara Rao Batchu,
• Ashok Ettam and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 64, doi:10.3762/bjoc.5.64

• reported for the class of compounds represented by B. One of the common methods used for the construction of a pyrone ring fused with benzene or with other heteroaryl moieties is Sonogashira-type coupling followed by electrophilic or transition metal mediated cyclization of the resulting alkyne (possessing

Palladium- catalyzed cross coupling reactions of 4-bromo- 6H-1,2-oxazines

• Reinhold Zimmer,
• Elmar Schmidt,
• Michal Andrä,
• Marcel-Antoine Duhs,
• Igor Linder and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2009, 5, No. 44, doi:10.3762/bjoc.5.44

• -substituted heterocycles 2a,b with phenylboronic acid in the presence of Pd(PPh3)4 and sodium carbonate at 80 °C in toluene gave the expected 4-phenyl-substituted 6H-1,2-oxazines 8a or 8b in 82 and 77% yield (Scheme 3). 4-Bromo-6H-1,2-oxazine 2a also serves as suitable model substrate for Sonogashira

• contrast, when the same reaction conditions were applied to the coupling of 2a and methyl propargyl ether, product 9d was obtained only in very low yield. In addition, Sonogashira coupling of 2a and methyl propargyl ether performed by an alternative protocol (Pd(OAc)2, CuI, PPh3, NHiPr2 in DMF) afforded

• the expected product 9d and a byproduct bearing a 4-enyne moiety at 4-position. This indicates an addition of a second alkyne molecule to the primary product 9. Similar results were observed for the Sonogashira reaction of 2a with propargylic alcohol [33]. After successful simple cross couplings of

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

• . (a) arylation at C-4 followed by alkynylation at C-2 or (b) alkynylation at C-2 followed by arylation at C-4. Methodologies based on strategy ‘a’ have been reported earlier. For example, Sonogashira coupling of a terminal alkyne with 2-chloro-4-aryl substituted quinoline [3] in the presence of (PPh3

• singlet at δ 8.03 assigned to the C-3 hydrogen of the quinoline ring. If the alkyne was at C-4, NOE enhancement at C-5 is expected in addition to C-3. It is note worthy that the use of the Sonogashira coupling or its modified form has been employed for the preparation of 2-alkynylquinolines or related

• in compound 3. The reaction mechanism of the present stepwise C–C bond forming reactions consisting of alkynylation followed by arylation is shown in Scheme 2. The Pd/C–Cu mediated coupling of 2,4 dichloroquinoline (1) with terminal alkynes (2) in water proceeds via normal Sonogashira pathway [6

Synthesis of novel photochromic pyrans via palladium- mediated reactions

• Christoph Böttcher,
• Gehad Zeyat,
• Saleh A. Ahmed,
• Elisabeth Irran,
• Thorben Cordes,
• Cord Elsner,
• Wolfgang Zinth and
• Karola Rueck-Braun

Beilstein J. Org. Chem. 2009, 5, No. 25, doi:10.3762/bjoc.5.25

• cyanation, carbonylation and Sonogashira cross-coupling starting from bromo-substituted naphthopyran 1 and benzopyrans 2a/b. A novel photoswitchable benzopyran-based ω-amino acid 6 for Fmoc-based solid-phase peptide synthesis is presented. The photochromic behaviour of the 3-cyano-substituted benzopyran 5a

• the presence of an Fmoc protecting group for the direct synthesis of ω-amino acid 6. Also, a Sonogashira reaction was conducted towards the synthesis of naphthopyran precursor 4, which is suitable for attachment to tripodal linker systems for the immobilization on surfaces [26]. Results and Discussion

• ]. However, only the rearranged and hydrodehalogenated benzofuran 14 was isolated in 65% yield after flash chromatography. Formation of the benzofuran can be rationalized by cleavage of the benzopyran ring and a subsequent rearrangement reaction [29][30]. However, by using standard Sonogashira conditions in