Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• -amine reduction and tosylation from diethyl (S)-2-(hex-5-en-2-yl)malonate ((S)-6). The stereocenter in geminal ester (S)-6 could be derived from (R)-2-methyloxirane ((R)-2) via a ring-opening reaction and a stereospecific inversion of the chiral secondary tosylate (R)-5. Following the similar procedure

• enolate of diethyl malonate yielded (S)-2-(hex-5-en-2-yl)malonate ((S)-6), and realized a stereospecific inversion of chiral secondary tosylate (R)-5 [30][31]. The geminal ester (S)-6 was next treated with NaOH in methanol to afford (S)-2-(hex-5-en-2-yl)malonic acid ((S)-7) in 96% yield [32]. Then

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• with enals having an aliphatic substituent in the β-position (entries 8 and 9, Table 5). The resolution of Michael adducts 14 and 15 derived from dimethyl and diethyl malonate has also been studied (Table 5, entries 14 and 15). Unfortunately, the retro-Michael reaction did not take place under the

• conditions tested. Similarly, the resolution of nitro aldehydes 16 and 17, prepared by Michael addition of nitromethane to α,β-unsaturated aldehydes (entries 16 and 17, Table 5), was tested, and the same results were obtained as in the cases of the malonate derivatives. These results indicate that dicarbonyl

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• synthesis of fluorinated cyclopentane products 41 from alkenyl malonate derivatives 40. The malonate nucleophile required longer reaction times of 8 hours compared to 1–3 hours for aminofluorination and oxyfluorination, however good yields were reported. Hypervalent iodine-mediated chlorocyclisation

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• , the molecular sieves were filtered off, and the filtrate was washed with water (50 mL × 2). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to afford diethyl α-acetoxy-α-(4-methylbenzoylamino)malonate (1a, 2.86 g, 8.1 mmol, 81% yield) as white solid. When

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• anionic species from, for example, malonate. One reason could be because of the formation of the less stable alkoxide by the progress of the nucleophilic addition. If this is really the case, the presence of the strongly electron-withdrawing fluorine-containing groups in our instance should nicely affect

• the characteristics of the resultant intermediate which could lead to the realization of the addition of such nucleophilic species. First of all, as shown in Table 4, we started to investigate the reactivity of 2b toward sodium malonate as the representative nucleophile. Because a brief solvent search

• indicated DMSO as the best for the attainment of high yields and diastereoselectivity (entries 1–5 vs 6 in Table 4), we further examined bases in this solvent to find out that t-BuOK behaved nicely, and the reaction of 2b with 2.0 equiv of diethyl malonate for 0.5 h at room temperature furnished 93% yield

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates 1–4 to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition

• by extended reaction times, sometimes up to 168 hours. An intriguing example involves the use of a bifunctional primary amine-sulfonamide catalyst, which activates benzylideneacetone towards dibenzyl malonate, with the presence of water accelerating the reaction [25]. An alternative approach, where

• acceleration of the reaction progress [26][27]. The crucial enhancement of anion stabilization by deprotonation of the methylene group in bisthiomalonates was hypothesized to surpass that of analogous dibenzyl malonate [28][29]. Surprisingly, the employment of NaH, NaSEt, or t-BuOLi as relatively strong bases

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• lead to a decrease in selectivity. Connon and co-workers have attached a cinchona thiourea organocatalyst to magnetic nanoparticles 13 for the Michael addition of dimethyl malonate (10) to trans-β-nitrostyrene (11) (Scheme 3) [31]. To explore the potential impact of nanoparticles on catalyst efficiency

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• . Addition of relatively weak H-donors such as diethyl malonate significantly increases the reduction current of S3 and shifts the potential value for 30 mV toward positive potentials (Figure 1b). In the reverse scan, a new peak appears, corresponding to oxidation of the malonate anion [23]; the peak of the

• useful compounds with multiple functionalities that were poorly available previously. CV curves for salt S2 and corresponding amine A2 (left, Figure 1a) and salt S3 with and without diethyl malonate additives (right, Figure 1b). (Pt, MeCN, 0.1 M Bu4NBF4, 0.1 V/s, vs Ag/AgCl, KCl(sat.). CV curves for

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• serine (Ser), a β-hydroxyaspartic acid (Hya), and a unique γ-amino acid biosynthetically originating from an arginine and a methyl malonate (4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid), with the amino group acylated by a saturated fatty acid. Subsequent HMBC and MS/MS analyses indicated that

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• run starting with malonate-tethered diyne 1b. In this case, the reaction was finished after 4 hours and bis(fulleroid) 2b was obtained with a 34% yield (Scheme 2). The corresponding compound 2b was analyzed by HPLC, giving only one peak. UV–vis experiments revealed the formation of a bis(fulleroid

• ) derivative (Figure S2 in Supporting Information File 1). The lower yield of 2b compared to 2a is probably due to the [2 + 2 + 2] homocoupling cycloaddition of the corresponding starting diyne, which is more favorable when the tether is a malonate rather than an NTs-sulfonamide. Among the four different [6,6

• has Cs symmetry [50], we can conclude that the major product formed was the α-isomer, as previously anticipated. All attempts to separate the two isomers by column chromatography and preparative TLC were unsuccessful. Malonate-tethered compound 2b had the same spectroscopic behavior as 2a though in

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• one-pot transformation from readily available benzyl(prenyl)malonate substrates. After the photooxygenation of the prenyl moiety, the resulting hydroperoxide was directly engaged in a Hock cleavage by adding a Lewis acid. The presence of an aromatic nucleophile in the reaction mixture and that of a

• extend the scope of this tandem reaction sequence towards analogous skeletons, we explored the effect of various substituents on the aromatic cycles. The successive prenylation and then diversity-oriented benzylation (n = 1 for substrates 11a–n) of diethyl malonate (10) afforded a variety of new

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• preserved, also with this mildly mismatched tether. The π-acidic NDI 61 with a Leonard-turned tertiary amine is a privileged small-molecule anion–π catalyst that catalyzes the enolate addition of malonate 4 with an activity that, however, does not reach that of the best carbon allotropes [95]. In the

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• the earlier report [15], under these conditions, formation of [(NHC)2Cu]+ complexes was not observed. In the same year, César et al. [26] reported in situ-generated malonate-derived anionic carbenes which reacted with CuCl to afford the anionic [(maloNHC)CuCl]Li complexes. Furthermore, zwitterionic

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• ][48][49][50]: 1) CuII → CuI → CuII; 2) CuI → CuIII → CuI; 3) CuII → CuIII → CuI → CuII. In 2006, Li et al. demonstrated that the CDC reaction of the C(sp3)–H bond of malonate diesters or other active methylene compounds with the C(sp3)–H bond adjacent to the oxygen atom of cyclic and open-chain

• involves a hydride abstraction from the benzylic site of isochroman to generate a cationic species A, whereas the malonate is activated by the In/Cu catalyst (B). Subsequently, the coupling of the two intermediates yields the desired product and regenerates the catalyst. Alternatively, In(III) may be

• ) from the DHP substrates to DDQ, a hydrogen atom transfer (HAT), and counter anion exchange of In(OTf)3 might happen to generate ion pair A. In(OTf)3 coordinates with the carbonyl oxygen atoms in dimethyl malonate 188 to provide activated complex B for subsequent addition to A furnishing product 189

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• (Figure 4) [100]. In the dimethyl malonate-derived ylide I-10, the σ-hole opposite the β-dicarbonyl was stronger with an electrostatic potential of 0.084 e, compared to the 0.049 e found for that opposite the arene. The same pattern was observed for the acetylacetone-derived ylide I-11, which possessed

• leading to malonate, the second equivalent of 31 coupled with the activated amine and cyclized to produce 33. The formation of 35 in their latter study was mechanistically analogous to this proposal; however, a third equivalent of ylide 31 was necessary to facilitate an additional series of PT and SET

• 44, from which reductive elimination of iodobenzene would generate 40. In 2021, Sen and Gremaud disclosed a blue LED-mediated formal C–H insertion reaction between iodonium ylides (e.g., 31) and pyrroles (e.g., 45), indoles and furans, producing malonate-substituted heterocycles 46 (Scheme 9) [126

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ) halogenation, and 3) ring closure (Scheme 2). β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate (3a) to afford adduct 4a, in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by

• nitronic acid furnishes cyclopropane 1a (method a) [1][4][12][13]. Halogenated malonate 6a [7][14][15][16][17] and nitrostyrene 7 [18] can also be used as substrates in this protocol (methods b and c, respectively). In these methods, diesters are mostly used as 1,3-dicarbonyl compounds, with acetylacetone

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• 24 was reported by Cong et al. [45] as a method for the synthesis of substituted dibenzo[b,f]oxepines 25 (Scheme 6). Treatment of the malonate derivative 24 with Mn(OAc)3 in 90% acetic acid gave C-10 carboxylate derivatives of dibenzo[b,f]oxepine 25. The authors proposed a one-electron oxidation of

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• ]oxazaphosphinin-4-ones (77) and bis(2,2,3,3-tetrafluoropropyl) 2-(4-chlorobenzylidene)malonate (78a) was kept at room temperature for 2 months, giving bis(2,2,3,3-tetrafluoropropyl) 3-(4-chlorophenyl)-2-phenyl/ethoxy-5-oxo-1-phenyl-1,3,5-trihydrobenzo[f][1,2]azaphosphepine-4,4-dicarboxylate 2-oxides (79) in good

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• each on the pyridine ring. Moreover, IPs with a non-aromatic C-2 substituent like an ester group were also included (4r). We also explored bromo analogues of other active methylenes such as ethyl cyanoacetate, ethyl acetoacetate, dimethyl, and diisopropyl malonates, as extension of diethyl malonate (4s

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• arylglyoxals to investigate the scope of substrates. No products were obtained in case of the acyclic CH-acids like dimethyl malonate, acetylacetone, and ethyl acetoacetate under the same conditions. The reaction follows almost the same mechanistic pathway that was previously mentioned as three-component

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• yields of the reactions with β-ketoesters and β-ketoamides were comparable with those obtained with 1,3-diketones. We also explored the reactions between 4-fluorophenyl hydroximoyl chloride (1a), which was the phenyl hydroximoyl chloride that gave the best yield, and diethyl malonate (2j) or dibenzyl

• malonate (2k) under the optimized reaction conditions. However, the reactions did not proceed (Figure 5). We suspected that the increased electron-donating effect on both sides of the 1,3-diketones in 2j or 2k made the methylene group less acidic, thus DIPEA was not able to deprotonate the methylene for

• mmol of 2, and 3 equivalents of DIPEA in 15 mL of 95% water, 5% methanol at room temperature for 2 hours. The yields were calculated after the isolation and purification of products. Reactions between 4-fluorophenyl hydroximoyl chloride (1a) and diethyl malonate (2j) or dibenzyl malonate (2k) did not

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• without any remarkable decrease in its catalytic activity. A novel cobalt catalyst with cobalt immobilized on nanochitosan fibers (Co-DMM@MNPs/chitosan) was fabricated using dimethyl malonate [36] and its applicability tested in a Sonogashira coupling reaction. The catalyst was found to be highly active

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• modify the triazolo[1,5-b][1,2,4,5]tetrazine ring system with a variety of structural fragments, thus enabling to vary their biological activity. The reactions of new triazolo[1,5-b][1,2,4,5]tetrazines with some CH-active compounds, such as malononitrile, ethyl cyanoacetate and diethyl malonate, have

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• hydroxyamination of oxindoles and β-ketoamides [49][50][51][52][53][54]. Recently, it has been shown that malonate derivatives such as malonate half thioesters and malonamides could be effectively used in various enantioselecive addition reactions [55][56][57][58][59][60]. In this context, Chen and co-workers

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• cyclization with the aryl ring constructs the 6-membered heterocyclic framework. In 2015, the Li group investigated the radical addition/cyclization of olefinic malonate and β-diketone compounds 96 with aldehydes 97 (Scheme 19) [97]. The reaction was feasible with ketones; however, lower product yields were

• observed. The efficiency of the reaction seems to be dependent on the deprotonation of the α-position of the olefinic malonate species. The authors noted decarbonylated products were obtained when cyclohexane carboxaldehyde and pivaldehyde were applied, consistent with the stability of the generated acyl