Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• aldehydes 224 generated terminal acetylenes 226 which cyclized with the second molecule of phosphonate 225 in the presence of Cu(I) to afford (5-methyl-1H-pyrazol-3-yl)phosphonates 230 in 46–81% yields (Scheme 46) [84]. Also, a domino reaction based on the dual reactivity of BOR as a homologation reagent as

• 1,2-dihydropyridine-3-phosphonate 259. Yavari et al. have described the phosphorylation of benzothiazole (263) and isoquinoline (246) through a one-pot three-component reaction with activated acetylenes 260 and diphenyl phosphonate (261) under solvent-free conditions at room temperature (Scheme 54

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• solvent also affect the enantioselectivity, with iPr2N(n-Pr) and CH2Cl2 proving best. Notably, only 1,2-addition was observed. With respect to the alkyne, activated terminal acetylenes, such as ynones and propriolates, are best for this reaction. Unactivated alkynes give products in reasonable yields (63

• –77%), but poor enantioselectivities (1–11% ee). However, the use of activated acetylenes provides a functional group handle for elaboration, which the authors demonstrate in the preparation of indolizidine 223AB. Building on their initial discovery of a non-asymmetric, copper-catalyzed, three

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• acetylenic dienophiles, other easily available acetylenes were used in the reaction with 1a. In all reactions attempted with phenylacetylene, (pyridin-2-yl)acetylene, and (tert-butyl)acetylene, no conversion of 1a was observed as evidenced by the blue color of the reaction mixture even after 24 h

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• significantly. We chose the Sonogashira coupling of diethynylcinnolines and alkylated diiodohydroquinone as a method for the formation of PAE’s backbone. It also should be mentioned that despite the fact that sila-Sonogashira coupling have been widely applied for the synthesis of different acetylenes with aryl

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• 11) produced by a combinatorial Glaser coupling of three different monomers (see Scheme 1). Growth inhibition of Bacillus subtilis by compounds 8a–j at 1 µM (15 h), and standard erythromycin at 1 µM (15 h). Combinatorial Glaser coupling involving acetylenes 7f, 7j and 7h. Synthesis of compounds 7a–j

Mono- and multilayers of molecular spoked carbazole wheels on graphite

• Stefan-S. Jester,
• A. Vikas Aggarwal,
• Daniel Kalle and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 2783–2788, doi:10.3762/bjoc.10.295

• ). Moreover, the six kinks that are seen in the STM images (one of which is marked by the white circle in Figure 2c and d) correspond (not to the carbazole units but) to the intersections of the terminal acetylenes of the rim segments. According to the space-filling model, only three of the four pseudo

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

• Shekaraiah Devari,
• Manjeet Kumar,
• Ramesh Deshidi,
• Masood Rizvi and
• Bhahwal Ali Shah

Beilstein J. Org. Chem. 2014, 10, 2649–2653, doi:10.3762/bjoc.10.277

• single step from a variety of acetylenes , i.e., arylacetylenes and most importantly aliphatic alkynes. Keywords: α-selective; C-alkynylation; glycal; metal free; TMSOTf; Introduction C-Glycosides represent an important class of carbohydrate mimics, owing to their presence in a large number of

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• substructure. The reactions have been found to be sensitive to the substitution of the ethynyl group. The formation of dienes with a zig-zag configuration is related to that observed for non-conjugated cyclic diynes of medium ring size. Keywords: acetylenes; dienes; [2.2]paracyclophane; selenium halides

• investigations on the intramolecular interaction of chemically disturbed functional groups in pseudo-geminally substituted [2.2]paracyclophanes, we report here the results of the addition reactions of selenium halides to pseudo-geminal bis(acetylenes). Results and Discussion Following our interest in the

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• analogue. The synthesized molecules are currently being screened for biological activities. We have also extended the reaction to triple-bonded electrophiles such as acetylenes, benzyne and nitriles; the results will be reported in due course. Studies are in progress to develop a stereoselective version of

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• function Analogues of PEMEDA and PEMPDA-β-CD with an azidoethane function attached to the terminal quaternary ammonium nitrogen were prepared as a basis for further derivatization. The azide functional group is reactive and can be used, for example, for the attachment of various substituted acetylenes by a

The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

• Joscha Vollmeyer,
• Ute Baumeister and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 910–920, doi:10.3762/bjoc.10.89

• detected in the GPC analysis. The template has therefore two effects in the cyclization: (1) The terminal acetylenes are hold in proximity, thus, an intramolecular reaction is favored over an intermolecular reaction. (2) If an intermolecular coupling has occurred, the template leads to easily separable

• longer intraannular alkyl bridge of 1b prevents a close packing of the rings and leads in this case even to the absence of the lc phase. Conclusion In summary, shape-persistent macrocycles with intraannular bridges were synthesized by oxidative Glaser-coupling of the appropriate acetylenes. The bridges

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• -ylidene with acetylenes. Indazol-3-ylidenes which possess an aryl ring at N1 rearrange to give substituted acridines by a ring-cleavage/pericyclic ring-closure reaction sequence (2→A→B→11) (Scheme 3). It proved to be advantageous to start these rearrangements from indazolium salts which are readily

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ]. Multicomponent reactions towards amide isosteres often involve an Ugi reaction followed by a Click reaction, in which two of the Ugi-inputs either contain an alkyne or an azide moiety. A well-known example of the latter reaction is the Copper(I) catalyzed azide–alkyne cycloaddition (CuAAC) between acetylenes and

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

• related cascade multicomponent processes of interest, which involve gold acetylides and imines. Among them, a new Au(I)-catalyzed entry to cyclic carbamimidates 17 starting from acetylenes, imines and p-toluenesulfonylisocyanate (18) was reported by Toste and Campbell [43]. The reaction gave mainly the 5

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• -pentynoic acid with aryl bromides, using a catalyst containing Pd(OAc)2 in combination with SPhos or XPhos in the presence of tetra-n-butylammonium fluoride (TBAF) as the base and THF as the solvent. Therefore, new efficient approaches to the synthesis of terminal acetylenes from widely available aryl

• terminal acetylenes is the most straightforward method for the preparation of substituted alkynes [1][2][3][4][5][6], which are extensively used as building blocks in a great number of applications including the synthesis of pharmaceuticals [7][8][9], natural products and organic functional materials [10

• presence of a Cu/Pd bimetallic catalyst, followed by the basic cleavage of the protecting group [42][43][44][45][46]. Terminal alkynes are often used as starting materials for the synthesis of disubstituted acetylenes through a second coupling process with another aryl halide. Decarboxylative couplings

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• molecules in the rate-determining step, respectively. Alternatively, there could be only one pathway including two acetylenes in the rate-determining step, which is inhibited by higher concentrations of the alkyne. The latter proposition is supported by the fact that commercially available copper acetylides

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• allowing the direct and regioselective C–H functionalization of benzofurans [12]. In this context, the introduction of an alkyne would be particularly useful, as acetylenes are important building blocks in synthetic chemistry, chemical biology and materials science [13]. Nevertheless, to the best of our

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• acetylenes [16]. The classical Huisgen reaction, thermally induced, gives an approximate 1:1 mixture of 1,4- and 1,5-disubstituted 1,2,3-triazole isomers (Scheme 1) [17]. However, when Cu(I) catalysis is applied, the reaction becomes regioselective, exclusively yielding the 1,4-regioisomer within a

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• with aryl acetylenes suggesting a strong halide effect and a sensitivity of the Pd–X bond under our reaction conditions. Indeed, the coupling of aryl acetylenes with bromo-anilines and bromo-phenols showed lower conversion compared to the iodo-congeners. We further evaluated the potential of our Pd–Cu

• /C catalyst for the alkynylation–cyclization of 2-iodophenols in view of preparing benzofurans. As already observed with the synthesis of indoles, aliphatic alkynes gave slightly lower yields than aryl acetylenes. A remarkable tolerance toward reactive functions such as ketones and alcohols

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• of the model probes retained good activity relative to the lead compound 2 with little to no cytotoxicity. Based on these results we decided to install acetylenes in our final probes through ether linkages at the positions of the methoxy groups of the most active models 8a, 8c and 14. Preparation of

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• carbamate moiety. Molecular structure of 9f (hydrogen atoms except of H9 and H10 are omitted for clarity). Possible regioisomers obtained in the carbocupration reaction of α-heterosubstituted acetylenes 1. Regioselective carbometallation of N-alkynylsulfonamide 2. Regioselective carbometallation of ynamide

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• the reactions of simple dialkylacetylenes, benzylzinc bromide was effective (Scheme 36, top). On the other hand, dibenzylzinc reagent was effective for the reactions of aryl(alkyl)acetylenes (Scheme 36, bottom). They applied the reaction toward the synthesis of an estrogen-receptor antagonist (Scheme

• -catalyzed carbozincation of arylacetylenes and its application to the synthesis of tamoxifen. Bristol-Myers Squibb’s nickel-catalyzed phenylzincation. Iron/NHC-catalyzed arylmagnesiation of aryl(alkyl)acetylene. Iron/copper-cocatalyzed alkylmagnesiation of aryl(alkyl)acetylenes. Iron-catalyzed

• and aryl(alkyl)acetylenes. Synthesis of estrogen receptor antagonist. Cobalt-catalyzed allylzincation of aryl-substituted alkynes. Silver-catalyzed alkylmagnesiation of terminal alkyne. Proposed mechanism of silver-catalyzed alkylmagnesiation. Zirconium-catalyzed ethylzincation of terminal alkenes

Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

• Andreas Unsinn,
• Cora Dunst and
• Paul Knochel

Beilstein J. Org. Chem. 2012, 8, 2202–2206, doi:10.3762/bjoc.8.248

• ][9]. The Normant carbocupration of terminal acetylenes allows the stereoselective preparation of trisubstituted alkenes with excellent E/Z ratio [10][11][12]. However, in order to obtain tetrasubstituted alkenes, a carbometalation of an internal alkene is required. This reaction is usually difficult

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• substituents has been prepared recently by a Zr-promoted linear coupling of different aryl and hetaryl acetylenes in high yield (Scheme 17) [66]. Treating, e.g., phenylacetylene (78) first with n-butyllithium and subsequently with bis(cyclopentadienyl)zirconium dichloride generates the trimeric metal complex

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• high yield and purity. Click reactions generally involve a Cu(I)-catalyzed version of the Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides (CuAAC), to regioselectively yield 1,4-disubstituted 1H-1,2,3-triazoles [11][12]. In the meanwhile, this type of click reaction has become very

• form co-oligomer 5. Synthesis of 1,4-disubstituted 1,2,3-triazoles from corresponding halides (1 equiv), terminal acetylenes (1 equiv) and sodium azide (2 equiv) in the presence of copper(I) iodide (10 mol %), sodium ascorbate (10 mol %) and N,N’-dimethylethylenediamine (DMEDA, 20 mol %) in ethanol