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

• complicates the recycling of the palladium catalyst since the two metals are difficult to separate. Sonogashira reactions can be used for the syntheses of terminal alkynes from aryl halides through the coupling with an alkyne source such as trimethylsilylacetylene (TMSA) or 2-methyl-3-butyn-2-ol (4) in

• 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

• obtained in a one-pot protocol with a considerable reduction of synthetic and purification steps with respect to traditional procedures [51][52][62]. Instead, when looking to the preparation of terminal alkynes from propiolic acid derivatives, the Cu-catalyzed protodecarboxylation of alkynoic acids [67][68

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• envisaged to evaluate the reactivity of internal alkynes towards the inverse electron-demand Diels–Alder reaction. To reach this goal, we decided to functionalize the alkynes 6–9 employing the Sonogashira cross-coupling reaction. Preparation of aryl-N-triazinylpentynamides The terminal alkynes 6–9 were then

Triphenylene discotic liquid crystal trimers synthesized by Co₂(CO)₈-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

• Bin Han,
• Ping Hu,
• Bi-Qin Wang,
• Carl Redshaw and
• Ke-Qing Zhao

Beilstein J. Org. Chem. 2013, 9, 2852–2861, doi:10.3762/bjoc.9.321

• applied to the synthesis of hexabenzocoronene DLCs through diarylethyne cyclotrimerization [51]. In this paper, we report four star-shaped DLC trimers with triphenylene discotic units by using a Co2(CO)8-catalyzed terminal alkynes [2 + 2 + 2] cycloaddition, and the trimers exhibit ordered rectangular

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

• this byproduct can be prevented by using copper(I) bromide instead of the iodide salt. This reactivity of 1-haloalkynes is in accordance with the observation that 5-iodo-1,2,3-triazoles are formed as byproducts, when CuI is used as catalyst in CuAAC reactions of azides and terminal alkynes as has been

• incorporation of iodide in CuAAC reactions of terminal alkynes mediated by CuI (1.0 equivalent) by adequate choice of the base present in the reaction mixture [141]. With a ratio of alkyne/azide/DMAP/CuI = 1.0/3.0/0.3/1.0, they obtained 96% of the 5-iodotriazole and 4% of the Glaser coupling product. Dzyuba has

• to be employed. Instead the presence of amine bases such as triethylamine or tris[(tert-butyl)triazolylmethyl]amine (TTTA) greatly accelerates the highly selective formation of the 5-iodo-1,4-disubstituted-1,2,3-triazoles (Scheme 14). Despite the many similarities to the CuAAC reaction of terminal

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• metal-acetylide with terminal alkynes, such as 40. The phosphine ligand had to be monodentate; bidentate ligands gave a lot lower yields. Their catalyst system worked very efficiently with many carbonyl electrophiles, also with Garner’s aldehyde (R)-1. The reaction of 1 with 40 gave 41 with high

Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

• Xiao-Ping Wang,
• Jin-Hong Lin,
• Cheng-Pan Zhang,
• Ji-Chang Xiao and
• Xing Zheng

Beilstein J. Org. Chem. 2013, 9, 2635–2640, doi:10.3762/bjoc.9.299

• aromatic alkenes with electrophilic trifluoromethylation reagents in the presence of copper and base. Results and Discussion Previously, we reported that copper powder or cuprous iodide could promote trifluoromethylation of heteroaromatics, arylboronic acids or terminal alkynes with trifluoromethyl

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• the reaction of commercially available 2-methyl-1-propenylmagnesium bromide with 2-bromobenzyl bromide in the presence of CuI and 2,2’-bipyridyl [32]. This aryl bromide could be coupled with selected terminal alkynes by using cesium carbonate as a base and PdCl2(MeCN)2/XPhos as a catalytic system [33

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• installation of a suitable leaving group sets the stage for the introduction of the first silylacetylene. Four different terminal alkynes 21 (a: Si = TMS; b: Si = SiMe2Ph; c: Si = SiMe2Bn; d: Si = Si(iPr)2H) were employed. Best results with yields of over 80% were obtained by the use of acetylene 21a

• , SiMe2Bn and Si(iPr)2OMe groups (Scheme 5). The best results were obtained with TMS-substituents. Although the SiMe2Ph-substituted product was not synthesized under optimal reaction conditions the desired product was formed in high yield. In addition, terminal alkynes were tolerated in the reaction

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• times, 15 mL), dried over Na2SO4, filtered and evaporated to afford the corresponding crude mixture which, in most cases, was pure enough to use in the next step without further purification. Iodination of terminal alkynes The starting alkyne (1 equiv; 2 mmol) was dissolved in acetone (10 mL). Then

• to flash chromatography to give substantially pure and optically active terminal alkynes with (R)-configuration. Cycloisomerization to give 3-iodo-2H-chromenes To a solution of the corresponding starting material 1 (1 equiv; 0.3 mmol) in dioxane (2 mL), under argon atmosphere, IPrAuNTf2 was added

Gold-catalyzed reaction of oxabicyclic alkenes with electron-deficient terminal alkynes to produce acrylate derivatives

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 1969–1976, doi:10.3762/bjoc.9.233

• Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, People’s Republic of China 10.3762/bjoc.9.233 Abstract Oxabicyclic alkenes can react with electron-deficient terminal alkynes in the presence of a gold catalyst under mild conditions

• derivatives in the gold catalyzed intermolecular reaction of oxabicyclic alkenes with electron-deficient terminal alkynes under mild conditions [69][70][71][72][73][74][75][76] (Scheme 1). Results and Discussion To generate a new C–O bond in the reaction of oxabicyclic alkene 1a with electron-deficient

• novel method to synthesize acrylate derivatives from oxabicyclic alkenes and electron-deficient terminal alkynes in toluene in moderate to good yields in the presence of the gold catalyst SPhosAu(MeCN)SbF6 under mild conditions. Efforts are in progress to elucidate the mechanistic details of this

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• . [47] have demonstrated that ethynyl ketones can be generated in flow by the palladium-catalysed acylation of terminal alkynes and further transformed in a continuous process to pyrazoles by cyclocondensation with hydrazines using a commercially available conductive heating modular flow reactor. Given

Bromination of hydrocarbons with CBr₄, initiated by light-emitting diode irradiation

• Yuta Nishina,
• Bunsho Ohtani and
• Kotaro Kikushima

Beilstein J. Org. Chem. 2013, 9, 1663–1667, doi:10.3762/bjoc.9.190

• Corey–Fuchs reaction [29], to obtain terminal alkynes. Although CBr4 has been used for various bromination reactions including radical brominations, these reactions need further additives to proceed. Here, we disclose the efficient bromination of saturated hydrocarbons, using CBr4 as a bromine source

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• reported that diphenyl(trimethylstannyl)phosphine reacts not only with terminal alkynes but also with internal alkynes and allenes (Scheme 4) [24][25]. It is noteworthy that the regioselectivity of the radical addition to propynamide is opposite to that of the relevant ionic Michael addition. Considering

• , which utilizes diphosphines generated in situ from chlorophosphine and hydrophosphine in the presence of triethylamine [28]. A variety of terminal alkynes undergo the radical diphosphination (Table 1). The diphosphination was applicable to the synthesis of a new push–pull-type molecule that emits blue

• studied the photoinduced radical chalcogenophosphination of alkynes and allenes by means of PhCh–ChPh/Ph2P–PPh2 binary systems (Ch = S, Se, Te) [30][37][38][39]. The regioselective outcome of the photoinduced thio- and selenophosphination of terminal alkynes (Table 5) is similar to that of the thermal

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• the cyclization step is an important factor to achieve the highly asymmetric induction. We next investigated the reactivity of internal alkynes as electron-rich acceptors (Scheme 6). The internal alkyne 14 has shown a good reactivity comparable to that of the terminal alkynes 6A–C. In the absence of a

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• preparative synthetic chemistry. Ozone was used to oxidatively cleave a variety of alkenes whereas oxygen was used to aid the oxidative homo-coupling of terminal alkynes (Figure 19). Our use of camera imagery became more sophisticated as we began to acquire data on the precise concentrations of the gases in

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• readily accessed from (S)-prolinol by using a modified known procedure [58]. Alkynylcarbamate 1j was achieved through the reaction of 3-bromo-1H-indole-2-carbaldehyde with the Ohira–Bestmann reagent followed by the addition of Boc2O. Terminal alkynes 1 were conveniently converted into allenic carbamates 2

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• ][28][29][30][31]. More recently, Kamijo, Yamamoto and co-workers [32] have developed a palladium-catalyzed cyclization of acetylenic aryl isocyanates in the presence of terminal alkynes. Halogenated arylpropionamides are commonly employed for the preparation of 3-alkenylindolin-2-ones involving tin

Titanium-mediated reductive cross-coupling reactions of imines with terminal alkynes: An efficient route for the synthesis of stereodefined allylic amines

• Kebin Mao,
• Guoqin Fan,
• Yuanhong Liu,
• Shi Li,
• Xu You and
• Dan Liu

Beilstein J. Org. Chem. 2013, 9, 621–627, doi:10.3762/bjoc.9.69

• Chemical Technology, Shenyang 110142, People’s Republic of China 10.3762/bjoc.9.69 Abstract Low-valency titanium species, generated in situ by using Ti(OiPr)4/2 c-C5H9MgCl reagent, react with imines to give a titanium-imine complex that can couple with terminal alkynes to provide azatitanacyclopentenes

• appeared in this report (1-octyne). Sato’s group further applied this reaction for the synthesis of optically active allylic amines with chiral imines and terminal alkynes [36]. However, the imine substrates employed in their reactions were all N-alkyl substituted ones [35][36]. Until now the scope and

• limitations for titanium-mediated reductive cross-coupling reactions of imines with terminal alkynes have been far less studied. Our group has developed a series of reactions using low-valency titanium reagents [37][38][39], including selective coupling of 1,3-butadiynes with aldehydes using Ti(OiPr)4/2 n

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

• reactions of simple terminal alkynes (Scheme 39) [121][122]. They proposed that the catalytic cycle (Scheme 40) would be triggered by the transmetalation of AgOTs with iBuMgCl to afford isobutylsilver complex 4C. Complex 4C would react with tert-butyl iodide to generate tert-butylsilver intermediate 4D

• . Carbometalation of terminal alkynes with 4D, probably by addition of a t-Bu radical, would yield vinylsilver 4E. Finally, transmetalation with iBuMgCl would give the corresponding vinylmagnesium intermediate 4g. Due to the intermediacy of radical intermediates, the carbomagnesiation is not stereoselective. In

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• )). Similarly, Patil and Raut [24] reported an elegant method for the synthesis of 2-substituted quinolines from 2-aminobenzaldehydes and terminal alkynes by a tandem A3/6-endo-dig-cycloisomerization (Scheme 1, (b)) using a cooperative catalytic system consisting of CuI and pyrrolidine. Prior to these two

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• -mediated cross-coupling between bromoalkynes 9 and nitrogen nucleophiles [42] turned out to be the most convenient one, the use of terminal alkynes [43], gem-dibromoalkenes [7], potassium alkynyltrifluoroborates [8] or copper acetylides [12] being less efficient when bulky N-Boc-allylamines 10 were used as

Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes

• Tsutomu Konno,
• Misato Kishi and
• Takashi Ishihara

Beilstein J. Org. Chem. 2012, 8, 2207–2213, doi:10.3762/bjoc.8.249

• [15][16][17][18][19][20][21][22]. Thus, treatment of 2,3,3,3-tetrafluoro-1-iodo-1-propene (1), which could be easily prepared from 2,2,3,3,3-pentafluoropropanol in three steps [23], with 1.2 equiv of terminal alkynes 2 and 1.5 equiv of Et3N in the presence of 5 mol % of Pd(OAc)2 and 10 mol % each of

• stereoselective manner. Finally, we attempted the Sonogashira cross-coupling reaction of the obtained iodide 13a (Scheme 4). Thus, treatment of 13a with 1.2 equiv of terminal alkynes and 40 equiv of Et3N in the presence of 10 mol % each of Pd(PPh3)4 and CuI in THF at 70 °C for 2–5 h gave the corresponding

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• of water occurred in the presence of TFA. The dehydrated products were obtained in 57 and 71%. The remaining material was the corresponding hydroxylated product. Parallel synthesis of a compound library A larger compound library was prepared by using resins 7 and 9, 15 different terminal alkynes 10f

• , DMSO-d6). Compounds 13, with the exception of compound 13f, were only characterized by mass spectrometry during the synthesis of the compound library. The copper-mediated [2 + 3] cycloadditions are restricted to terminal alkynes. However, the ruthenium-catalysis allows the use of internal alkynes. In

• – Huisgen 1,3-dipolar cycloaddition of solid-phase-immobilized azides with terminal alkynes by copper(I) catalysis: An azide-functionalized Wang resin 7 or 9 (1 equiv) was preswollen in dimethylformamide (1.5 mL/100 mg resin) for 2 h at room temperature. The copper(I) catalyst was prepared in situ by using

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins

• Nianhong Lu,
• Lihong Wang,
• Zhanshan Li and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 192–200, doi:10.3762/bjoc.8.21

• terminal alkynes to give the doubly alkyl-substituted acetylenes [1][2][3]; the Brønsted acid and Lewis acid catalyzed coupling of alcohols with indoles to give the 3-alkyl-substituted indoles [4][5][6]; and the Brønsted acid and Lewis acid-catalyzed coupling of alcohols with 1,3-dicarbonyls to give the 2

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• either from direct cyclization or from a formal rearrangement of the carboxamide group. Terminal alkynes are essential to achieve bicyclic pyrrolo-fused pyridinones by a 6-exo-dig process, while the presence of a phenyl group at the C–C triple bond promotes the 7-endo-dig cyclization giving pyrrolo

• terminal alkynes with pyrroles is shown in Scheme 2. It is highly probable that the products arise from the vinyl gold species B and F, in turn generated from alkynes 4 after coordination to AuCl3. The formation of F can result by a migration of the acyl group from the spiro center of the transient