Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• as N-phenylmaleimide, maleic anhydride, and methyl propiolate resulted in the formation of the corresponding bis-spirocyclic cycloadducts (Scheme 1b). It is clear that PRP has been studied in reactions with a small number of dipolarophiles. Accordingly, it is impossible to fully evaluate the

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• inhibited the desired phosphinylphosphination (see, alkyne 2f), probably because of the decomposition of Ph2P(O)PPh2. Furthermore, an electron-deficient alkyne such as methyl propiolate (2h) failed to provide the desired adduct (3h) [61]. 3-Phenyl-1-propyne (2i) and cyclohexylacetylene (2j) gave 3i and 3j

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• -bistriazolylpurine derivatives 2a–c were obtained in the synthetic procedures developed by us before [11][14][67]. The CuAAC reaction was performed between diazide derivatives 1a and 1b and phenylacetylene or methyl propiolate (Scheme 2). SNAr reactions between bistriazolylpurine derivatives and O-nucleophiles were

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• -purine (5, 0.76 g, 2.53 mmol, 1.0 equiv) in DCM (35 mL), followed by the addition of triethylamine (0.39 mL, 2.78 mmol, 1.1 equiv), methyl propiolate (0.68 mL, 7.59 mmol, 3.0 equiv), and acetic acid (0.16 mL, 2.78 mmol, 1.1 equiv). The reaction mixture was stirred for 2 h at room temperature. Then, the

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• -catalyzed nucleophilic alkyne addition of methyl propiolate, provided ynone 139 in 86% yield over two steps. When, compound 139 was treated with (+)-diisopinocampheylchloroborane (DIPCl) [75][76] at room temperature and the resulting mixture was processed as in the usual manner using diethanolamine, the

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• of such cases where an aryl radical, formed via the photocatalyzed reduction of diazonium salt 2.1+, added to methyl propiolate. Ensuing cyclization of the resulting vinyl radical 2.2· finally yielded the desired phenanthrene 2.3 [41]. A different approach involves the intramolecular cyclization of α

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• of the obtained succinic anhydride derivative (16b) upon purification. Other unsymmetrical dienophiles (methyl acrylate, methyl propiolate) gave complex mixtures of regio- and/or stereoisomers. The reaction of lynestrenol enyne 6a with N-phenylmaleimide was also performed to furnish compound 17a in

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• performed a Suzuki coupling reaction between boronic acid 15 with chloro compound 2 (Scheme 2). To the best of our knowledge, there is no report of a Suzuki coupling reaction using boronic acid 15 in the literature. However, we generated this required boronic acid from the corresponding methyl propiolate

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• ][150][159][164][175][211] derivatives [174][183][200][229] are often used as the complementary dienophiles (Scheme 14, reaction pathways (i), (ii) and (iii), respectively), as well as mono- and disubstituted acetylene derivatives, such as methyl propiolate [229] and dibenzoylacetylene [150]. Conversely

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• Huisgen et al. found that some non-symmetrical alkynes (oct-1-yne, phenylacetylene and especially methyl propiolate) gave mixture of both pyrazole regioisomers. The following Table 4 summarizes all known examples [1][2][8][20][24][32][33][34][36][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80

• regioselectivity of sydnone cycloadditions with methyl propiolate pointed out that the reason for the lower regioselectivity can also be attributed to the low-lying HOMO of this dipolarophile. While for the LUMO-controlled reaction (type III) only the 3-substituted pyrazole is expected to be the main product, for

• –LUMO energy gaps and terminal orbital coefficients can be tuned by substitution of the sydnone (and alkyne) the ratio of both isomers is often only slightly influenced. For example 3-(substituted phenyl)sydnones react with methyl propiolate to give a mixture of both regioisomers in a 75:25 ratio (for

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• tubular reactor with 1 min residence time at 25 °C in DMSO medium. This resulted in quantitative yield. The amide synthesis is carried out simultaneously by mixing methyl propiolate (1.5 equiv) and aqueous ammonia (6 equiv) solution in a T-mixer followed by a coiled reactor. The authors report over 95

• variable. Simultaneously methyl propiolate and aqueous ammonia can be precooled at 0 °C using a compact heat exchanger (it can even be a coil inside a jacket) before mixing at the desired molar ratio using a ratio control. The amide can be monitored at the reactor outlet using inline monitoring system

Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• via reacting methyl propiolate with (azidomethyl)benzene. This promising catalytic behavior of complex 4 prompted us to extend our studies toward a one-pot synthesis of 1,2,3-triazoles from alkyl halides, sodium azide, and alkynes. The three-component version has already been successfully performed

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

• the application of a [2 + 2 + 2] cycloaddition sequence (Scheme 45). To this end, [2 + 2 + 2] cycloaddition of 1,10-diyne 274 was carried out with methyl propiolate (275) in the presence of a cationic rhodium(I)-(S)-BINAP complex (10 mol %) as a catalyst. The desired [2 + 2 + 2] cycloaddition was

• of the planar-chiral carba-paracyclophane 278 by using the cationic rhodium(I)/(S,S)-bdpp-catalyzed [2 + 2 + 2] cycloaddition of cyclic diyne 277 with terminal methyl propiolate (275) under high substrate concentration conditions (Scheme 46) [179]. Shibata and co-workers [180] have synthesized chiral

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

• examine the reactions of diverse hetaryl thioketones with both 2a and methyl propiolate (2b). Moreover, along with standard procedures, the high-pressure technique was applied. Finally, selected examples of the obtained polycyclic 2H-thiopyrans were oxidized to give the corresponding sulfones. Results and

• pressure of 5 kbar. After 72 h, the corresponding thieno[2,3-c]thiopyran 4e was obtained in 35% yield (Scheme 2). In an extension of the study, reactions of methyl propiolate (2b) with selected aryl and hetaryl thioketones were performed under thermal and high-pressure conditions. The reaction of 1a with

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• extensively delocalised. To the best of our ability we could not find a single previous published example of a Michael addition employing 4-hydroxy-2-pyrones. Initial experiments reacting 4-hydroxy-2-pyrone 3a with methyl propiolate (6a) in the presence of an amine base afforded only moderate yields of

• . Following reaction optimisation, we applied these conditions to a number of different propiolate esters and alkylated 4-hydroxy-2-pyrones (Table 3). Surprisingly, the tolerance of the reaction to different ester groups proved rather limited. The switch from methyl propiolate to tert-butyl propiolate (6b

• . Changes in the C-6 substituent on the pyrone were tolerated much better, with yields from good to excellent for a range of pyrones with methyl propiolate (Table 3, entries 5–8). A further attempt with pentafluorophenyl propiolate resulted in a poor yield (Table 3, entry 9). As an extension to this

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• latter gave slightly better yields, it was argued that the dissolved air contributed to the product formation. A Cu(II)–TMEDA catalyzed tandem phosphorus–carbon bond formation–oxyfunctionalization was developed [245]. When methyl propiolate was subjected to the same reaction conditions only the β-adducts

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

• , −78 °C → rt (80%) [70]; (c) n-BuLi, 35, HMPT, THF, −78 °C (87%) [71]. (a) cat. Rh(acac)(CO)2, 42, THF, 40 °C (74%). (a) 1-PropynylMgBr, CuI, THF, Me2S, −78 °C (95%); (b) Ethynyltrimethylsilane, EtMgBr, CuI, THF, Me2S, −78 °C (82%) [72]; (c) EthynylMgCl, ZnBr2, toluene, −78 °C [73]; (d) n-BuLi, methyl

• propiolate, Et2O, −78 °C → 0 °C, then (S)-1 at −20 °C (62%) [74]. (a) cat. 50, toluene, 0 °C (52%); (b) cat. 51, toluene, 0 °C (51%); (c) cat. 52, toluene, 0 °C (50%). (a) (iPr)3SiH, cat. Ni(COD)2, dimesityleneimidazolium·HCl, t-BuOK, THF, rt. (a) Cp2Zr(H)Cl, cat. AgAsF6, CH2Cl2, rt; (b) Cp2Zr(H)Cl, 1

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

• formed by a regioselective opening of the oxygen bridge in substrate 1a. Intermediate A releases a proton to afford intermediate B. Intermediate B attacks methyl propiolate, which is activated by the gold catalyst, to generate gold vinyl complex C. In intermediate C, the ester group and the naphthalene

• ring are on the same side, yielding the final product 3a with (Z)-configuration via protodeauration. The alkyne ketone 3i is more electron-deficient and more reactive than methyl propiolate and it is more difficult to coordinate by the gold complex. Therefore, with alkyne ketone 2i as a substrate

• HP-5989 instrument. General procedure for the reaction catalyzed by Au(I) catalysts Into an oven-dried reaction flask under Ar gas protection was added oxabicyclic alkene (0.2 mmol), Au catalyst (0.001 mmol), methyl propiolate (0.4 mmol) and toluene (1.0 mL). The reaction mixture was stirred at room

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

• Li-Juan Zhang Qun Wu Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.97 Abstract In the presence of triethylamine as catalyst, the one-pot four-component reactions of arylamines, methyl propiolate, isatin and

• reactions of arylamines, methyl propiolate, aromatic aldehydes and malononitrile (ethyl cyanoacetate) and successfully developed a facile synthetic procedure for functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones]. Results and Discussion The efficient formation of

• 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

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• been used like 176 include cyanoacetylene and methyl propiolate. A third group of pericyclic reactions of conjugated bisallenes that has been studied thoroughly concerns various cheletropic cycloadditions. The earliest studies in this area involve the addition of sulfur dioxide to different alkyl and

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

• formation of β-enamino ester by the reaction of arylamine with methyl propiolate requires a relative long time [38][39][40][41][42]. Thus, under our previously established reaction conditions a molar excess of p-toludine (4.0 mmol) and methyl propiolate (2.0 mmol) reacted in ethanol at room temperature

• published domino Povarov reaction [45][46][47][48][49]. At first, arylamine adds to methyl propiolate to form the β-enamino ester A. Secondly, excess arylamine reacts with the aromatic aldehyde to form the N-aryl aldimine B in the presence of p-toluenesulfonic acid as catalyst. Thirdly, the Mannich type

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• , intermolecular [2 + 2] cycloaddition reaction between 2,3-pentadiene and methyl propiolate [10]. In summary, there are only a few general methods to prepare carbocyclic spirooxindoles non-racemically [11][12][13][14]; we have demonstrated the first thermal, intramolecular [2 + 2] cycloaddition reaction of an

Radical cascades using enantioenriched 7-azabenzonorbornenes and their applications in synthesis

• David M. Hodgson and
• Leonard H. Winning

Beilstein J. Org. Chem. 2008, 4, No. 38, doi:10.3762/bjoc.4.38

• electrophile trapping with the sulfone corresponds approximately to the rate of hydrogen atom transfer from (TMS)3SiH. Attempted reaction with methyl vinyl ketone, N,N-dimethylacrylamide and methyl propiolate gave rearranged-reduced azacycle 8 in modest yields, as well as small quantities of hydrosilylated