Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• halides [93][94], bromoalkynes [95], bromoalkanes [96], and pyridyl thioesters [97] (Scheme 26A). Likewise, the Rousseaux group has recently documented the arylation of NHPI esters obtained from cyclopropanecarboxylic acids [98] and malonic acid half amides [99], while the Reisman lab has pioneered an

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

• ][56][57]. Anion–π catalysis on fullerenes has been introduced in 2017 [12]. Fullerene anion–π catalysts were developed with the benchmark reaction introduced two years earlier (Figure 2) [2]. In this reaction, at the beginning of all biosynthesis, finetuned malonic acid half thioesters 4 [58][59][60

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• . Consequently, we applied the cyclohexyl derivative of Meldrum’s acid 15, which exhibits enhanced solubility in non-polar solvents [36]. The Meldrum’s acid derivative 15 was synthesized from malonic acid and cyclohexanone using acetic anhydride and sulfuric acid as a catalyst (see Supporting Information File 1

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

• heteroleptic Cu(I) complexes combining the malonic acid-derived anionic NHC and a neutral imidazol-2-ylidene were also obtained in a very selective manner (Scheme 12). As discussed later, many of these complexes were employed as catalysts. In 2015, Collins et al. [27] compared the stability and reactivity of

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• reaction [33]. Thus, Knoevenagel condensation using the diaryl ether 29 and malonic acid gave the corresponding α,β-unsaturated compound 30, which was submitted to a concomitant hydrogenation of the double bond and the nitro group to give compound 31. Sequential diazotization/halogenation and

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• tetraaminobisthiourea chiral macrocycles as catalysts in decarboxylative Mannich reactions. Low macrocycle loading was used to catalyze the decarboxylative addition of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. It was reported that effective activation

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• decarboxylation of the malonic acid derivative 42 to give pent-4-enecarboxylic acid (43). In many cases, the flow protocol provided improved yields compared to the corresponding batch syntheses. Palladium-catalyzed cross-coupling reactions require higher temperatures and thus can be realized in an inductively

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• ) and in the substitution pattern of the macrocycle (R = H or iPr in the 3,5-positions of the phenylene linkers, for 56 or 57; see Figure 14). These heterobifunctional chiral catalysts were studied for the asymmetric Michael addition of malonic acid diethyl ester (59) to cinnamaldehydes 58. While the

• for the non-interlocked mixture, see Figure 15). DFT calculations showed that the reaction takes place by cooperative action of the Li phosphate macrocycle and the amine thread, enabled by the mechanical bond. The Li phosphate acts as a Lewis acid to activate the malonic acid diethyl ester, which is

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• . Only 5 mol % of the optimal macrocycle catalyst efficiently catalyzed the decarboxylative addition of a broad scope of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. The rigid macrocyclic framework and the cooperation between the thiourea and

• report a systematic synthesis of tetraamino-bisthiourea chiral macrocycles and their performance in catalyzing the decarboxylative Mannich addition of malonic acid half thioesters (MAHTs) to isatin-derived ketimines. The macrocycle-enabled hydrogen-bonding activation network and the associated confined

• and activation ability. Catalytic reaction optimization The synthesized macrocycles were then applied as catalysts in the decarboxylative addition of malonic acid half thioesters (MAHTs) to isatin-derived ketimines [48]. The reaction between ketimine 6a and MAHT 7a was initially performed in THF at

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• , iron(III) chloride hexahydrate, trifluoroacetic acid (TFA), N-trifylphosphoramide (NTPA), benzoic acid, diphenyl phosphate (DPP), malonic acid, chloroacetic acid, copper(II) triflate, acetic acid, and p-toluenesulfonic acid (p-TSA) were used as catalysts. TFA gave the best yield of these catalysts with

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• Tania Xavier Sylvie Condon Christophe Pichon Erwan Le Gall Marc Presset Université Paris Est Créteil, CNRS, ICMPE, 2 rue Henri Dunant, F-94320 Thiais, France 10.3762/bjoc.17.135 Abstract The use of mono-substituted malonic acid half oxyesters (SMAHOs) has been hampered by the sporadic references

• to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an

• intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials. Keywords: alkylation; esterification; malonate; saponification; SMAHO; Introduction Malonic acid half oxyesters (MAHOs), also

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• -withdrawing and electron-donating substituents were well tolerated in either coumarin or imine portion, and electron-withdrawing substituents at ortho-position of the imine phenyl ring afforded the corresponding products with excellent yields and moderated to good ee. The asymmetric addition of malonic acid

• -hydroxycoumarins (1) and aromatic imines 63 promoted by cupreine (65). Asymmetric addition of malonic acid half-thioesters 67 to coumarins 66 using the sulphonamide organocatalyst 69. Enantioselective 1,4-addition of azadienes 71 to 3-homoacyl coumarins 70. Michael addition/intramolecular cyclization of 3

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• resulting compound was considered as a starting material for synthesizing 2-(perfluorophenyl)malonic acid by hydrolysis. It was found that the desired 2-(perfluorophenyl)malonic acid could not be obtained from this ester by hydrolysis, neither under basic nor under acidic conditions. Nevertheless

• . Keywords: decarboxylation; fluorinated aromatic compounds; hydrolysis of esters; 2-(perfluorophenyl)acetic acid; 2-(perfluorophenyl)malonic acid; Introduction 2-Phenylmalonic acid (1) and its esters are useful and versatile intermediates in the synthesis of many practically important compounds, e.g

• range by fluorination (directly or indirectly) of initial organic molecules. In the ongoing project, we are interested in synthesizing 2-(perfluorophenyl)malonic acid (2, Figure 1) as a new ligand for the preparation of 3d and 4f heterometallic coordination compounds. Results and Discussion To our

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• hydrodecarboxylation product 55. Nicewicz and co-workers also reported the decarboxylation of carboxylic acids and malonic acid derivatives catalyzed by an acridinium photoredox catalyst (Mes–Acr–Ph) and PhSSPh in 2015 (Scheme 20) [27]. This direct method of the organocatalytic decarboxylation of carboxylic acids to

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• acid diethyl esters (2, Scheme 2) [43]. This strategy provided a novel, convenient and efficient approach to construct 2-(3,4-dihydronaphthalen-2-yl)malonic acid diethyl esters 3. The MCPs 1 with the electron-deficient or electron-rich groups were all suitable for this reaction system. The mechanism

• for the Mn(OAc)3-mediated oxidative radical ring-opening and cyclization of MCPs with malonates is outlined in Scheme 2. Initially, the malonic acid diethyl ester (2) was transformed into radical 4 [44] under the action of Mn(OAc)3. Then, the selective addition of the radical 4 to the C–C double bond

• olefins and cyclopropanols) over the last 20 years. Review Oxidative radical ring-opening and cyclization of methylenecyclopropanes (MCPs) In 2004, Huang and co-workers reported the first manganese(III) acetate-mediated radical ring-opening and cyclization of methylenecyclopropanes (MCPs, 1) with malonic

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• magnesium enolate of malonic acid half ester, prepared in situ from potassium methyl malonate, MgCl2 and triethylamine in acetonitrile, was added [24][25]. The acylation of magnesium methyl malonate by the preformed imidazole 3 led to the desired bifunctional starting material 4 in good yield (79

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• malonic acid and its mono(thio)esters have been poorly investigated so far despite the potential to become a convenient route to β-trifluoromethyl-β-amino acid derivatives and to their partially saturated heterocyclic analogues. Results: In this paper we show that 4-trifluoromethylpyrimidin-2(1H)-ones

• , unique heterocyclic ketimines, react with malonic acid under organic base catalysis to regioselectively provide either Michael- or Mannich-type decarboxylative addition products depending on solvent polarity. Malonic mono(thio)esters give exclusively Michael-type products. The two regioisomeric products

• synthesis of novel isomeric 4(6)-trifluoromethylated 1,2,3,4-tetrahydro- and perhydro-(2-oxopyrimidin-4-yl)acetic acid derivatives. Keywords: ketimines; malonic acid; Michael- and Mannich-type decarboxylative addition; pyrimidin-2(1H)-ones; regioselectivity; trifluoromethyl group; Introduction

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• likely to involve a nitrosoalkene intermediate, which is generated upon the action of TBAF or the anion of the 1,3-dicarbonyl compound on N,N-bis(silyloxy)enamine 3. Unlike malonic acid derivatives and β-keto esters, 1,3-diketones produced only complex mixtures of products in the reaction with N,N-bis

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• oxidation of malonic acid (MA) [68][69]. Translation from the reaction scheme or equations (back) to the network motif, however, is far from intuitive. Hence, despite its beauty and obvious potential for making exciting discoveries, the BZ reaction (and similar classical chemical systems [70][71][72][73

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• reaction of malonic acid with chlorobenzaldehyde [21]. In the first step, the substrates reacted in the presence of formic acid and diethylamine to form 3-chlorophenylpropionic acid followed by a intramolecular Friedel–Crafts acylation with malonyl chloride in the presence of zinc chloride to give 5-chloro

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• heating isatine with malonic acid followed by esterification of the produced quinoline carboxylic acid with methanol in the presence of sulfuric acid at 80 °C for 6 h. 4-Arylphthalazin-1(2H)-ones A7 and A8 [24][25] were prepared by Friedel–Crafts acylation reaction of N-aminophthalimide with either

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• anodic decarboxylation of five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22–69% yield with a

• /b, 16a/b and 18a/b supports this assumption. The cyclic voltammogram of 18a/b shows an oxidation peak at 1.75 V to 1.85 V (Figure 3). In the cyclic voltammogram of malonic acid derivative 16a/b a peak appears at a potential of 2.4 V (Figure 3). The malonic acid derivative 15a/b does not show any

• of malonic acid derivatives [33]. In the literature, there are only a few examples where menthol auxiliaries have been used to control the stereochemistry in radical reactions [34]. In first experiments using (−)-menthol (1) as a chiral auxiliary we observed a low but nevertheless promising

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• ][16][17] or from their reduction products, chiral α-amino alcohols [9][18]. In contrast, our approach used the racemic ester rac-12 of β-phenylalanine, easily accessible in a Knoevenagel-type condensation of benzaldehyde 11, ammonium acetate and malonic acid, followed by esterification (Scheme 1) [20

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

• reaction was performed under mild conditions using PTSA·H2O as the additive. Subsequently, the asymmetric aldol reaction of aliphatic aldehydes with isatins was achieved by the same group by using a structurally slightly modified organocatalyst (cat. 5, Scheme 18) [34]. Malonic acid as the additive and

• anhydrous EtOH as the solvent were found to be critical for achieving high yields and enantioselectivities. However, only 33% ee was obtained for 5-methylisatin under the same conditions. A plausible transition-state model was proposed and examined by DFT calculations, in which malonic acid formed two

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• recovered methyl ester of 9 (60% ee), although high yields were observed (Table 3, entry 1). Then, in another attempt, the malonic acid 10 was subjected to the reaction with carbonyldiimidazole (CDI) under different conditions but also in combination with a piperazine. This method has been reported for a