Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• carbon atom in the 2’-position are an indium-mediated alkynylation and a 1,3-dipolar cyclization. Keywords: alkynylation; antiviral; cancer; C-nucleosides; ribavirin; Introduction The triazole nucleoside ribavirin (RBV, Figure 1) is used for the treatment of a number of viral infections and may be

• of antivirals due to their stability in biological fluids and their bioavailability. Some years ago, we described an approach leading to the C-ribosylated analogue 1 of ribavirin (Figure 2) with the key-steps of the synthesis being an indium-mediated alkynylation of a ribose derivative followed by

• commercially available 2-C-methyl-1,2,3,5-tetra-O-benzoyl-β-D-ribofuranose (4) as shown in Scheme 1. Debenzoylation of 4 followed by selective protection led to derivative 5, which was submitted to the indium-mediated alkynylation reaction affording the alkynyl riboside 6 with the same β-anomeric selectivity

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• ], mercury [26], cobalt [27], iridium [28], ruthenium [29], indium [30] etc. Other methods towards the synthesis of propargylamine include: alkynylation of imine [31][32][33], enamine [34], and Csp³–H bonds adjacent to N-atoms [35][36]. In the A3 coupling, the role of the metal catalyst is believed to

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• state for the observed stereoselectivity. Pyrrole attacked the ketone from the Si face to generate (R)-3-pyrrolyl-3-hydroxyoxindoles. Very recently, Feng et al. revealed that the bifunctional guanidine (L3)/CuI catalyst can catalyze asymmetric alkynylation of isatins with terminal alkynes, affording

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• is highly attractive, but the use of a carbon linker is usually required. Herein, we report the gold-catalyzed direct alkynylation of tryptophan in peptides using the hypervalent iodine reagent TIPS-EBX (1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one). The reaction proceeded in 50–78% yield

• using a linker is used, for example an alkylation reaction of cysteine. The direct introduction of an alkyne onto the biomolecule would be interesting to profit from modified electronic and spectroscopic properties. However, the direct alkynylation of peptides or proteins is usually based on the use of

• the Sonogashira reaction, which requires modified non-natural amino acids [32][33]. In 2013, our group reported the alkynylation of thiols using the hypervalent iodine reagent TIPS-EBX (1a, 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one) (Scheme 1A) [34]. The reaction was almost

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• PMB group, because the oxidation potential of DMB ethers is lower and the cleavage was expected to be more facile [45]. Indole synthesis from DMB-protected 13 and subsequent Boc protection afforded 16 (58%). Alkynylation and desilylation of 16 to 19 and coupling of 19 with ketone 6 proceeded smoothly

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

• -based catalysts [9][10][11][12][13][14][15]. Among these, chiral copper catalysts have been used with remarkable success in the alkynylation of cyclic iminium ion and oxocarbenium ion intermediates. This review will focus on the development of these enantioselective, copper-catalyzed alkynylations

• , this reaction can be carried out in H2O, as well as PhMe. Nearly simultaneously, Knochel’s group reported an enantioselective CuBr/Quinap-catalyzed alkynylation to deliver propargylic amines with alkyl substitution at the stereocenter (Scheme 2) [18][19][20]. In this reaction, proton transfer from the

• for enantioselective alkynylations of cyclic electrophiles. The first enantioselective, copper-catalyzed alkynylation of a cyclic iminium ion was reported by Li’s research group in 2004 [22]. Building on their development of a cross-dehydrogenative coupling (CDC) reaction between benzylic amines and

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• alkene C–H bonds, and the alkynylation reactions by making use of direct transformations on the alkyne C–H bonds such as Sonograshira, Glaser couplings were extensively studied and utilized [69][70][71][72]. Under the inspiration of these well-known reaction models, the amidation reaction based on the

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• aldehyde fragment 6 by asymmetric alkynylation, and form the pyran using an oxa-Michael addition, in a manner reminiscent of that employed by Uenishi and co-workers [34]. Finally, macrocyclisation will be achieved through the well-established strategy of ring-closing metathesis at C8–C9. Results and

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• ketimine is followed by stoichiometric alkynylation with a trimethylsilyl-protected alkynyllithium reagent. Removal of the silyl and sulfinyl protecting groups allows for CuAAC with a resin-bound azide. Acylation of the amine followed by dehydration yields the active alpha-tetrasubstituted triazole [7

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• sulfonamide derivative in preparing glycophane molecule (Scheme 6). Haley and Langsdorf [90] have reported the synthesis of a cyclophane-containing octacobalt complex 49 using the Glaser–Eglinton coupling reaction [91] as a key step (Scheme 7). In this regard, palladium-catalyzed alkynylation of 1,4

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• , utilizing a Trost hydrosilylation and protodesilylation as key reactions. Keywords: alkynylation; chiron approach; Ferrier-type C-glycosylation; macrolide; Introduction Aspergillides A, B and C (Figure 1) (three, novel, bicyclic, 14-membered macrolides with 2,6-cis or trans-fused di- or tetrahydropyan

• compound was also characterized by 2D NMR studies wherein significant NOESY correlations were observed for the C2 proton and the methylene protons of the carbinol moiety present on C6. Also, the NOESY correlation was absent between the C2 proton and the C6 proton (Figure 2). After the alkynylation reaction

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• tolerated a wide range of organometallic nucleophiles [32] and Yu developed methodology for THIQ alkynylation which does not require N-aryl motifs [33]. We sought a general procedure for organometallic trapping of iminium salts generated by oxidative functionalisation; a methodology amenable to a range of

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

• , India 10.3762/bjoc.10.277 Abstract A novel metal-free strategy for a rapid and α-selctive C-alkynylation of glycals was developed. The reaction utilizes TMSOTf as a promoter to generate in situ trimethylsilylacetylene for C-alkynylation. Thanks to this methodology, we can access C-glycosides in a

• 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

• biologically active natural products, such as palytoxin, spongistatin, vitexin, orientin, bergenin and halichondrin [1][2][3][4][5]. Over the years myriad methods have appeared for their efficient and stereoselective synthesis [6][7][8][9][10][11][12]. Among these methods, C-alkynylation [13][14][15][16] is of

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• stereocontrolled nucleophilic alkylation [15][16][17][18][19], alkynylation [20][21], 1,2-addition [22][23][24][25][26] and aldol reaction [27][28][29][30][31][32] have been developed. Various nucleophiles such as organometallics, boronic acids and unsaturated ketones can be tolerated in this context (Figure 2

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• reaction. Merging Au-based photoredox catalysis and Lewis base catalysis for the Mannich reaction. Merging Ru-based photoredox catalysis and Cu-catalyzed alkynylation reaction. Merging Ru-based photoredox catalysis and NHC catalysis. 1,3-Dipolar cycloaddition of photogenically formed azomethine ylides

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

• Yifan Li Jerome Waser Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH4306, 1015 Lausanne, Switzerland 10.3762/bjoc.9.204 Abstract The direct alkynylation of benzofurans was achieved for the first time using the hypervalent iodine

• reagent 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one (TIPS-EBX) based on the cooperative effect between a gold catalyst and a zinc Lewis acid. High selectivity was observed for C2-alkynylation of benzofurans substituted with alkyl, aryl, halogen and ether groups. The reaction was also

• successful in the case of the more complex drug 8-methoxypsoralen (8-MOP). Keywords: alkynylation; benzofurans; cooperative catalysis; direct functionalization; gold catalysis; hypervalent iodine; Introduction Benzofurans are important heterocycles frequently encountered in both bioactive compounds and

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

• /bjoc.9.160 Abstract This paper describes the preparation of indoles, azaindoles and benzofurans in pure water by using a new heterogeneous Pd–Cu/C catalyst through a cascade Sonogashira alkynylation–cyclization sequence. Details of the optimization studies and the substrate scope are discussed. This

• ][7]. A detailed survey of the recent literature revealed that both indoles and benzofurans can be attained by a cascade Sonogashira alkynylation–cyclization sequence (Scheme 1). Many efficient catalytic systems have been reported since the pioneering studies of Yamanaka [8] and this approach is now a

• role of copper is twofold since it acts not only as a cocatalyst for the alkynylation reaction but also as a Lewis acid for the cyclization step. Procedures involving heterogeneous catalysts have been much less explored and essentially limited to the use of heterogeneous Pd catalysts in the presence of

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• -Alkynylated glycals were obtained in very good yields whereas the alkynylation in position 2 gave poorer results. Chemoselective reduction of the triple bond in the resulting enyne system by the action of Raney-Ni furnished enol ethers, which could be readily refunctionalized. Methanol proved to be an

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

• . Deviating from the general procedure, in the case of m-bromo-iodobenzene (1d) only 1 equiv of TMSA was added in order to minimize a second alkynylation at the bromine position in the initial Sonogashira coupling step, which resulted in a moderate yield of the dibromo derivative (2d). Upon reaction of the m

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

• - and pyrazolylazulenes through the use of glyoxylation–decarbonylative alkynylation–cyclocondensation sequences starting from azulene or guaiazulene as substrates, gives rise to the formation of the target compounds in moderate to good yields. Keywords: azulenes; catalysis; decarbonylation

• alkynylation transform [47] back to azulenes. Previously, glyoxylation of azulene (1a), with oxalyl chloride in 1-position was reported to be essentially complete within 5 min [39]. Oxalyl bromide could be equally used as a glyoxylating agent [49][50]. Likewise, the glyoxylation of 1b has been reported to

• by our smooth glyoxylation–alkynylation sequences with a variety of unfunctionalized π-nucleophiles, such as pyrazoles, thiophenes, furans, and even the hydrocarbon azulene (1a) [53], we decided to perform optimization studies of the glyoxylation–decarbonylative alkynylation with guaiazulene (1b), a

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

• . A gold-catalyzed direct alkynylation of indole and pyrrole heterocycles 204 with a benziodoxolone-based hypervalent iodine reagent 203 has been developed [91]. The functional group tolerance was greatly increased when compared with direct alkynylation of indoles reported previously. Kar et al

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

• -pot procedure with the Au(I)-catalyzed C3-selective direct alkynylation of indoles using the benziodoxolone reagent TIPS-EBX to give a mild, easy and straightforward entry to 2-substituted-3-alkynylindoles. The reaction can be applied to unprotected anilines, was tolerant to functional groups and easy

• to carry out (RT, and requires neither an inert atmosphere nor special solvents). Keywords: alkynylation; direct functionalization; gold; hypervalent iodine; indoles; Introduction Indoles are widespread in both natural products and synthetic drugs [1][2] and as a result, their synthesis and

• alkynylation with bromoacetylenes [29]. New methods are needed to expand the scope of this transformation and Au catalysis appears especially promising, due to its broad functional groups tolerance, which could allow the direct use of unprotected anilines. Recently, the direct alkynylation of preformed

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

• -alkynylthieno[2,3- d]pyrimidines were prepared via alkynylation of 4-chlorothieno[2,3-d]pyrimidines in good to excellent yields. Some of the compounds synthesized were tested for cytotoxic activity in vitro. Keywords: catalysis; C–C bond; copper; palladium; thieno[2,3-d]pyrimidine; Introduction Alkynyl

• 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

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• review. A related cationic Ru-vinylidene complex was used for an efficient alkynylation of pyridines with (alkyn-1-yl)trimethylsilane [98]. Based on these preliminary results, various catalytic propargylations of arenes have been developed, employing catalysts such as Mo/chloranil [16

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

• above proving inefficient, palladium chemistry was subsequently considered. The vinyl bromide 24a was reported to participate in Sonagashira alkynylation chemistry; however, yields of the resultant enyne were low [20]. Therefore, we decided to investigate Suzuki–Miyaura cross-coupling reaction as a