NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• -dimethylfuran with dimethyl acetylenedicarboxylate in toluene was studied. With this system the authors could optimize the reaction conditions in a rapid manner with the consumption of very small amounts of solvent and reagents (Figure 12c). It is interesting to note that this set-up worked with standard, non

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

• , resulting from reaction of isocyanide with dialkyl acetylenedicarboxylate, added to the carbonyl group of the acylphosphonate followed by an intramolecular cyclization. A palladium-catalyzed isocyanide-based three-component pathway into phosphorylated quinazolines has been described by Wu et al. [80]. The

• -component reaction of acylphosphonates, isocyanides and dialkyl acetylenedicarboxylate to afford 2-phosphonofuran derivatives. Synthesis of (4-imino-3,4-dihydroquinazolin-2-yl)phosphonates via an isocyanide-based three-component reaction. Silver-catalyzed three-component synthesis of (2-imidazolin-4-yl

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• acetylenedicarboxylate (DMAD, 129) to generate the tetracyclic system 130 (Scheme 27). To design synthetically challenging oxa-bowls, Kotha and Ravikumar [31] have utilized the RRM and ERRM of extended norbornene systems. The key building blocks such as 133 and 134 were prepared from a readily available DA adduct 131

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

• -trimerization of two different alkynes with a high chemo- and regioselectivity. The Rh(I)/H8-BINAP complex catalyzed the partially intermolecular cyclotrimerization of 1,9-decadiyne (271) and diethyl acetylenedicarboxylate (272) to give [6]metacyclophane derivative 273 (Scheme 44) [177]. This approach is also

• applicable to synthesize various polyether-based cyclophanes. In this report, they have synthesized various polyether containing cyclophanes by a cross-cyclotrimerization catalyzed by a cationic rhodium(I)/H8-BINAP complex as a key step. The ether linked α,ω-diynes and dimethyl acetylenedicarboxylate were

• acetylenedicarboxylate (DMAD) to deliver compounds 332a,b (77%). These DA adducts were irradiated in diethyl ether/dichloromethane (5:1) to offer the corresponding bioxaquadricyclane 333, subsequent thermolysis gave the bioxepine 334 (81%). Finally, aromatization of bioxepine 334 with trifluoroacetic acid (TFA

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• this series (Scheme 12). Again, we do not attempt to describe the exact stereochemical outcome of the addition, since the experimental evidence is too meagre. Exploratory cycloaddition experiments were carried out with dimethyl acetylenedicarboxylate and maleic anhydride, but none of these dienophiles

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• fewer intermediate purification steps. Diester 8 can be prepared from commercially available ethylene trithiocarbonate (9) and dimethyl acetylenedicarboxylate (10) at around 100 g scale in 74% yield (based on previously reported large-scale syntheses [31][32]). We have scaled up the reduction of 8 using

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

• sulfones. Keywords: dimethyl acetylenedicarboxylate (DMAD); hetero-Diels–Alder reactions; high pressure reactions; methyl propiolate; thioketones; thiopyrans; Introduction A series of recent publications evidence that, in contrast to earlier opinions, thioketones are useful building blocks for the

• studies [7][8]. Moreover, thiobenzophenone (1a) was reported to react as a heterodiene smoothly with cyclooctyne, dicyanoacetylene, and dimethyl acetylenedicarboxylate (2a) to give [4 + 2] cycloadducts of type 3a, which spontaneously rearrange via a 1,3-hydrogen shift yielding rearomatized products of

• the molecular structure of one of the symmetry-independent molecules of 6d, drawn using 50% probability displacement ellipsoids. Hetero-Diels–Alder reaction of thiobenzophenone (1a) with dimethyl acetylenedicarboxylate (2a) [10]. Synthesis of polycyclic thiopyrans via the hetero-Diels–Alder reaction

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• Chao Wang Yan-Hong Jiang Chao-Guo Yan College of Chemistry & Chemical Engineering Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.10.281 Abstract The one-pot four-component reaction of benzohydrazide (2-picolinohydrazide), acetylenedicarboxylate, isatins and malononitrile (ethyl

• cyanoacetate) with triethylamine as base catalyst afforded functionalized 1-benzamidospiro[indoline-3,4'-pyridines] in good yields. 1H NMR spectra indicated that an equilibrium of cis/trans-conformations exist in the obtained products. Keywords: acetylenedicarboxylate; benzohydrazide; 1,4-dihydropyridine

• reactions [19][20][21]. Recently, we and Perumal have demonstrated that the four-component reaction of arylamine, acetylenedicarboxylate, isatin and malononitrile can afford the spiro[indoline-3,4’-pyridine] derivatives in satisfactory yields [22][23][24]. We envisioned that functionalized spiro[indoline

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• -(methoxycarbonylmethyl)benzimidazolium bromides with dimethyl acetylenedicarboxylate (DMAD) in presence of K2CO3 in DMF [7] or in presence of triethylamine in acetonitrile [8] give a mixture of pyrrolo[1,2-a]benzimidazole (2–7%) and a compound whose formation involves the loss of an alcohol molecule for which different

• reactions, but they could not be always isolated from the reaction mixtures. Due to the high reactivity of dimethyl acetylenedicarboxylate which can react also with the starting 1-substituted benzimidazole, the one-pot three-component synthetic procedure starting from almost equimolar amounts of 1

• -substituted benzimidazole 1, ethyl bromoacetate and dimethyl acetylenedicarboxylate (3d) in 1,2-epoxybutane led to a complex mixture of reaction products. However, by direct reaction of 1-benzyl-3-ethoxycarbonylmethylbenzimidazolium bromide, obtained previously from 1-benzylbenzimidazole (1a) and ethyl

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• annulation of N’-(2-alkynylbenzylidene)hydrazides followed by an 1,3-dipolar cycloaddition. Results and Discussion Based on Wu’s work on the silver triflate-catalyzed tandem reaction of N’-(2-alkynylbenzylidene)hydrazides with dimethyl acetylenedicarboxylate [28], we started our research by examining the

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

• reaction involving nitriles 52 as pro-nucleophiles (Scheme 28) [71]. Wu and co-workers successfully employed the isoquinolinium-2-ylamides 43 as an ylidic species in two-component tandem [3 + 2]-cycloaddition reactions with a series of substrates including dimethyl acetylenedicarboxylate [72

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• 33a and 33b (Scheme 9, Figure 10). In an exploratory study aimed at expanding the chemistry shown in Scheme 4, we observed that diethyl acetylenedicarboxylate (DEAD, 4b) does not react with benzylidenemalononitrile (7a) in the presence of L-proline. However, when DABCO was employed as the amine

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• Hong Gao Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.330 Abstract The four-component reaction of 2-aminobenzothiazole, aromatic aldehydes, acetylenedicarboxylate and piperidine or pyrrolidine in ethanol afforded the

• synthesis of a versatile heterocyclic system, herein we wish to report the interesting results of the four-component reaction of secondary cyclic amines, acetylenedicarboxylate, 2-aminobenzothiazole and aromatic aldehydes and the efficient synthesis of the complex 2-pyrrolidinones containing both

• benzothiazolyl and piperidinyl (or pyrrolidinyl) units. Results and Discussion Initially, we set out to investigate the reaction conditions by using piperidine to react with dimethyl acetylenedicarboxylate to give the expected β-enamino ester. It is interesting to find that the reaction of piperidine with

One-pot cross-enyne metathesis (CEYM)–Diels–Alder reaction of gem-difluoropropargylic alkynes

• Santos Fustero,
• Paula Bello,
• Javier Miró,
• María Sánchez-Roselló,
• Günter Haufe and
• Carlos del Pozo

Beilstein J. Org. Chem. 2013, 9, 2688–2695, doi:10.3762/bjoc.9.305

• diethyl acetylenedicarboxylate (DEAD) afforded adduct 3c in 51% yield, and no aromatization was observed during the process (Table 1, method A, entry 3). When maleic anhydride was used as dienophile, the corresponding diacid 3f, arising from the anhydride ring opening under the reaction conditions, was

The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives

• André S. Kelch,
• Peter G. Jones,
• Ina Dix and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 1705–1712, doi:10.3762/bjoc.9.195

• acetylenedicarboxylate (22) with dimethyl malonate (23) under the catalytic influence of pyridinium acetate, the fully substituted cycloheptadienes 24 and 25 (Scheme 5) were produced; both authors also proposed reaction mechanisms for this complex transformation that can be considered as reasonable even today; for the

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

• -aminocyclohexanecarboxylates 11–14 were prepared previously by a diastereoselective epoxidation of the corresponding 2-aminocyclohexenecarboxylates, followed by a regioselective oxirane ring opening with NaN3 [68]. Three different alkynes (phenylacetylene, diethyl acetylenedicarboxylate and ethynyl ferrocene) were employed as

• cases; Table 1, entries 3 and 4). 1,4,5-Trisubstituted 1,2,3-triazoles are of notable importance in drug discovery. For example, several 1,2,3-triazole-4,5-dicarboxylates display significant antituberculotic activity in vitro [69]. Thus, a nonterminal alkyne, diethyl acetylenedicarboxylate, was

• dipholarophiles, it must be taken into account that the carboxylate groups of diethyl acetylenedicarboxylate and the aromatic system of the ferrocenyl group as ligands can probably coordinate copper from its matrix. Therefore, the concentration of the catalytically active Cu(I) species is increased as compared to

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• functionalized spiro[indole-3,4’-pyridines] via the four-component reaction prompted us to study the reaction scope further [25]. Another widely used electron-deficient alkyne reagent, methyl propiolate, was utilized to replace dimethyl acetylenedicarboxylate as one component. The addition reaction of aniline to

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• forward to explain the product formation (Scheme 1). On the basis of the well-established chemistry of amines and DMAD [29][30], the reaction between 1,2-diaminobenzene and dimethyl acetylenedicarboxylate (2a) affords dihydroquinoxaline 5. Compound 5 possesses enamine character and, thus, can readily

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• [39] and of diethyl acetylenedicarboxylate [40] has been achieved by dialkylzinc-mediated radical additions. Worthy of note is that in some cases the zinc-atom-transfer-based carbozincation of alkynes can occur with anti selectivity [38][40], and thereby represents a complementary approach to

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• three-component reaction of arylamine, isatin and cyclopentane-1,3-dione. Results and Discussion Recently we found that the four-component reactions of arylamine, acetylenedicarboxylate, isatin and dimedone in acetic acid resulted in the novel functionalized tetrahydrospiro[indoline-3,2’-quinoline

• ] derivatives in moderate yields (Scheme 1a) [15]. In order to explore the generality of this four-component reaction, the reactivity of the other cyclic 1,3-diketones was also investigated. In an exploratory experiment, the four-component reaction of p-methoxyaniline, dimethyl acetylenedicarboxylate, 1-benzyl

• -5-methylisatin and cyclopentane-1,3-dione in acetic acid was carried out at room temperature. After workup, we were a little surprised to find that there was no unit of acetylenedicarboxylate in the obtained product (Scheme 1b). In another experiment, the three-component reaction of isatin

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• electron-deficient alkynes, such as methyl propiolate or dimethyl acetylenedicarboxylate [27][28][29][30], have shown versatile reactivity and have been widely used as key intermediates in a number of domino reactions to construct heterocyclic systems [31][32][33][34][35][36][37][38][39][40][41][42

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• -phthalimidocarboxylic esters [18][19], treatment of diazoester 8a with catalytic Rh2(OAc)4 in the presence of an equimolar amount of N-phenylmaleimide (NPI) or dimethyl acetylenedicarboxylate (DMAD) produced the cycloaddition products 18 and 19, respectively (Scheme 7). The signal sets of sulfonium ylides 12aA and 12aB

Valence isomerization of cyclohepta-1,3,5-triene and its heteroelement analogues

• Helen Jansen,
• J. Chris Slootweg and
• Koop Lammertsma

Beilstein J. Org. Chem. 2011, 7, 1713–1721, doi:10.3762/bjoc.7.201

• , such as with N-phenylmaleimide and dimethyl acetylenedicarboxylate, providing single anti-adducts (e.g., 14; Scheme 4) [61][69]. Theoretical calculations on model structures showed the anti cycloaddition to be the kinetically controlled path and the syn addition the thermodynamically favoured one [40

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

• indenes 40 is observed upon introduction of ester and phenyl substituents on the cyclopropene (Scheme 7). AuPR3NTf2 complexes (PR3 = 41–45) are selective catalysts for the intermolecular hydroalkoxylation of electron-poor alkynes of type R−C≡C−EWG and dimethyl acetylenedicarboxylate [33]. In reactions of