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

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

• describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access

• 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

• (SMAHOs) [8][9][10], or disubstituted MAHOs [11], has been only occasionally reported. Bibliographical data indicate that SMAHOs can be accessed by different routes (Scheme 1). The most classic one is the alkylation of a dialkyl malonate, followed by a monohydrolysis of one ester group. The alkylation is

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

• resulted in products with moderate to excellent yields and enantiomeric excesses as shown in Scheme 16. Enders et al. developed the enantioselective synthesis of cyclopenta[c]-fused chromenones 54 starting from hydroxylated malonate 53 with enals 2 [50]. The reaction stands out for its good to excellent

• hydroxylated malonate 53 catalyzed by NHC 55. Oxidative [4 + 2] cycloaddition of enals 57 to coumarins 56 catalyzed by NHC 59. Asymmetric [3 + 2] cycloaddition of coumarins 43 to azomethine ylides 60 organocatalyzed by quinidine 62. Synthesis of α-benzylaminocoumarins 64 through Mannich reaction between 4

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• to form 2-fluoro-2-nitropropane in a 40% yield (Scheme 1). The reaction with sodium diethyl malonate was also reported to produce the difluoromalonate, but in a very low yield of ca. 5%. N-F amine 1-1 is very volatile (bp 49.5 °C), and could only be prepared in 7.5% or 13% yield by electrochemical

• -fluoropiperidine (1-1) [21] and then in 1991, Banks et al. reported the improved yields of the reactions of 1-1 with sodium salts of 2-nitropropane, malonate esters, and a keto ester, and phenylmagnesium bromide [22]. However, the fluorinated products were still accompanied by considerable amounts of byproducts

• -rich substrates such as sodium diethyl (phenyl)malonate, 1-morpholinocyclohexene, phenol, and anisole (Scheme 47). The fluorination power of the carboxamide 21-2 was less than that of its N-F sulfonamide analog 11-2. 1-22. N,N’-Difluoro-1,4-diazoniabicyclo[2.2.2]octane salts In 1996, Umemoto and co

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• silica are suggested to play a key role in the water elimination step. Furthermore, the primary amine function on the silica shows better outcomes compared to a tertiary amine. Different products were prepared in moderate to excellent yields, however, with the less acidic diethyl malonate the catalyst

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• literature, several strategies are reported using the sulfinyl group [84][85][86][87][88]. In this context, an enantioselective synthesis of 4-substituted azetidin-2-ones 52 was also accomplished starting from chiral imines 14 and dimethyl malonate (49). A diastereoselective coupling of these components

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• presence of a catalytic amount of piperidine afforded pyridopsoralen 22 in 46% yield. Analogously, pyridopsoralen 23 was prepared from 16 by Knoevenagel condensation with diethyl malonate and subsequent lactonization with 62% yield (Scheme 4) [13]. To the best of our understanding, the scaffolds 21–23 are

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• first time reported a microwave-assisted four-component domino reaction involving acyclic 1,3-diketones 54, amines 32, diethyl malonate (126) and triethyl orthoformate (111) for the synthesis of substituted pyridone derivatives 127 at 120 °C under catalyst- and solvent-free conditions. The reaction

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• CBr4 or I2, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or NaH as the base, and a malonate-derived substrate. The adduct is synthesized in a slightly higher yield by direct treatment of fullerene with malonates. As noted above, a decrease in the strain of the fullerene core is the driving force of its

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

• transformation into a C–C bond. Compounds containing electron-withdrawing groups such as malonitrile, dimedone, ethyl cyanoacetate and diethyl malonate were used as C-nucleophiles. Transformations were performed in DMF in the presence of NaH and the products were obtained in high yields (Scheme 6). The lower

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• -difluorocyclopropanecarboxylic acid derivatives 58 by the Michael addition of ester and amide enolates to 2,4,6-trimethylphenyl 4-bromo-4,4-difluorocrotonate (57) followed by an Et3B-initiated radical cyclization (Scheme 24) [68]. Furthermore, when the sodium salt of dimethyl malonate was used as the Michael donor the

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• leading to the observed regioisomers of the isoprenyl esters. All acids shown were found in form of their isoprenyl esters. (Z)-9-Hexadecenoic acid is obtained from palmitic acid by a Δ9-desaturase (ds). Malonate elongation and reduction (red) leads to (Z)-3-hydroxy-11-octadecenoic acid, an intermediate

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• third bands in between the spectra in water and in those with the conjugate Dex-1b solution [37]. The I1/I3 of pyrene was 1.1 in water, while in the conjugated dextran solution it was 1.5, a value which is comparable with solvents like diethyl malonate, dioxane, or dimethoxyethane, all organic solvents

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

• General and Inorganic Chemistry, Russian Academy of Sciences, Leninskiy prospect, 31, Moscow, GSP-1, 119991, Russian Federation 10.3762/bjoc.16.153 Abstract Diethyl 2-(perfluorophenyl)malonate was synthesized in 47% isolated yield by the reaction of sodium diethyl malonate and hexafluorobenzene. The

• surprise, 2-(perfluorophenyl)malonic acid (2) was not described in the literature to date. The only reference to this compound actually concerned the formation of the anion from diethyl 2-(perfluorophenyl)malonate (3) with excess NaH [21]. At the same time, diethyl 2-(perfluorophenyl)malonate (3) is a

• readily accessible compound. Diethyl 2-phenylmalonate (4) is usually obtained (Scheme 1) by condensation of ethyl phenylacetate (5) and diethyl carbonate under basic conditions [22] because of the low reactivity of bromobenzene in noncatalytic nucleophilic reactions with sodium salts of diethyl malonate

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• , the reaction of dimethyl malonate-derived fluoroaromatic enynes 16 afforded the corresponding cyclopentenone products 17 in higher yields (85–92%). Thus, the reaction of enynes bearing fluorinated groups attached to the alkyne moiety was found to afford the corresponding cyclized products in moderate

• which they detailed the Markovnikov hydrofluorination of alkynes using HF.DMPU coupled with a gold catalyst [60]. Accordingly, the appropriate propargylmalonate derivatives were fluorinated to give fluoroalkene intermediates, which were then converted into malonate-based enynes 37 (Z = CO2R) through a

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• ) [19], N-methyl-2-pyridone 7 (δ 139.5) [20], 2,4-dimethoxy-3-methylquinoline (8, δ 147.0) [21], and 2-methoxypyridine 9 (δ 147.2) [22] supported a 2-quinolone form 1 but not 2-quinolinol 2 (Figure 2, Table 1). The same structure was synthesized from diethyl malonate and aniline (see Supporting

• methyltransferase [27]. Entry of malonate as the acylate precursor into this pathway is proposed to yield 3 (4 in the original literature) [29]. Thus, 1 is very likely to be biosynthesized by the same mechanism followed by additional methylation on C3. Compound 1 is reportedly inhibitory to Mycobacterium

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• with benzyl bromides 14b and 14d, respectively (Scheme 5). Pyrrole 16c was synthesized by Knoevenagel reaction of 13a with dimethyl malonate [42]. The Pd(0)-catalyzed cyclization of 8k and 8l required a temperature of 140 °C, but provided pyrrolo[2,1-a]isoindoles 18d and 18e, respectively, in good

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• formation [20]. As this biosynthesis is based on iterative cycles, the polyamine biosynthesis shows a similar pattern [22][34][35]. The elongation with one to three malonate units by the type I PKS FclK for product diversification is unusual. However, multiple examples for bacterial iterative type I PKS are

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• reactions between N-phenyltetrahydroisoquinoline and dimethyl malonate, nitromethane, indoles, and dialkyl phosphonates furnished the α-substituted N-phenyltetrahydroisoquinolines in yields equal or better than with the originally used photocatalysts, such as eosin and Ir-complex [29][30][31] (Scheme 10

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• between diethyl malonate and nitrostyrene to afford only one of the two (S)-11 and (R)-11 enantiomers, depending on the redox state of the copper center. The reaction was run with a 5 mol % catalyst loading and a base (Et3N) and was compatible with different solvents (THF, MeCN, CH2Cl2 and hexane

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• monochloroacetic acid have been published. The production of basic building blocks like glycine [5] (>600 000 tons/year in China in 2015) and diethyl malonate from monochloroacetic acid show the value of this compound as a starting material. Many reactions with monochloroacetic acid, including the synthesis of

• glycine and diethyl malonate, are based on nucleophilic substitution of the chlorine [6][7][8][9][10]. In an attempt to find new synthetic applications of monochloroacetic acid we turned our attention to photoredox catalysis. We were inspired by the rebirth of visible light photoredox catalysis, induced

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• in Scheme 13. The successful use of α,β-unsaturated acylimidazole in Cu ECAs using organometallic reagents has been introduced very recently. Pioneering works in this field were published in 2011 by Roelfes, Liskamp, and co-workers, with the 1,4-addition of dimethyl malonate to cinnamyl 2-acyl-1

• ECA of Grignard reagents to 3-boronyl α,β-unsaturated thioesters. Cu ECA of alkylzirconium reagents to α,β-unsaturated thioesters. Conversion of acylimidazoles into aldehydes, ketones, acids, esters, amides, and amines. Cu ECA of dimethyl malonate to α,β-unsaturated acylimidazole 31 with

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• (25%) were obtained (Table 2). In pure CH2Cl2 as solvent there was only a small conversion, but no product 14 detectable. Only the debrominated diethyl malonate was identified as side product. This makes conclusively clear that the solvent DMF is needed for this type of photoredox reaction. The

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• oxidative conditions has been developed. The employment of Mn(OAc)3·2H2O or KMnO4 as stoichiometric oxidants allowed the use of a wide range of nucleophiles, such as nitromethane, (aza)indoles, pyrroles, phenols, pyrazole, indazole and diethyl malonate. The formation of the target compounds presumably

• diethyl malonate, providing compounds 14a–c in 40–58% yields. To conclusively reveal the scope of the reaction, we exploited N-cyanomethyl quaternary salts of fused thieno[2,3-c]pyridine 15 and 1-methyl-6-azaindole 16 in this transformation. Therefore, annulated chromenoimidazoles 17–20 were effectively