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

• with benzyl chloroformate (Scheme 2b). The benzyl malonates 5 and 6 are converted to the corresponding benzyl malonyl chlorides with thionyl chloride. To these at −40 °C the auxiliary menthol (1), 8-p-anisylmenthol (4) [19], 8-methylmenthol (2) [20] or 8-phenylmenthol (3) [21] was added in the presence

• of triethylamine, whereby the menthyl esters 7–12 were obtained in good yield after flash chromatography as a mixture of two diastereomers (Scheme 1). The benzyl menthyl malonates 7–12 were hydrogenated under atmospheric pressure to afford the free carboxylic acids 13a/b–18a/b in high yield and

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• co-workers demonstrated that chiral lanthanum and samarium tris(BINOL) complexes (Figure 3), developed by the Shibasaki group for asymmetric Michael additions using malonates and organometallic reagents, are effective catalysts for the sequential conjugate addition of 4-tert-butyl(thiophenol) to α,β

• enantioselective Friedel–Crafts addition of pyrroles to imides 84. Kobayashi’s enantioselective addition of malonates to α-substituted N-acryloyloxazolidinones. Chen and Wu’s enantioselective addition of thiophenol to N-methacryloyl benzamide. Tan’s enantioselective addition of secondary phosphine oxides and

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• reaction of N-methyl arylamines and monoalkyl malonates/cyanoacetic acids. Under optimized conditions A and B, various β-N-arylamido esters and nitriles (3) were subjected to a one-pot alkylations using 1.2 equivalents of KOt-Bu to produce C-alkylated intermediate 5 followed by oxidative coupling using 1.2

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• substrate; however, to date, the carbonyl components for these reactions are mostly restricted to 1,3-diones, β-ketoesters, malonates, α-cyanoacetates, 3-substitued oxindoles and related systems. Generally, enolizable esters or carboxylic acid derivatives have been challenging in this strategy, because

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• higher than 90:10, although the stereoselectivity for the reaction leading to 4ag, with two contiguous tertiary–quaternary stereocenters was only moderate (dr 75:25, entry 8 in Table 2). The main difference in those additions was related with the reaction time, because the less reactive malonates (2b and

• diastereoselectivity for the reaction of 1a with 2g (dr 74:26), but the yields for the reactions with 2-substituted malonates (2b–d) were only moderate (entries 9–11 in Table 2). Next, we extend the study to the reaction of different β-functionalized cycloalkanones (3a–c), 2-acetylcyclopentanone (3d), and 2-acetyl-γ

• enantiomeric excess was determined by chiral-phase HPLC analysis using mixtures of hexane/isopropanol as eluent. Parent and supported bifunctional thioureas used in this work. Reaction of nitrostyrene with diethyl malonate and 2-ethoxycarbonyl cyclopentanone. Reaction of nitrostyrenes with malonates and β

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• malonates 6, to obtain 3,4,4-trisubstituted cyclohexanones 7 [17]. It is noted that the organocatalyst employed is the same with the previous example, catalyst 4. Furthermore, this reaction is taking place in the presence of PPY and high pressure was utilized. The authors proposed that PPY deprotonates the

• malonates 65 to 3-nitro-2H-chromenes 66, which provided the substituted chromanes 67 in moderate to excellent yields and good enantioselectivities (Scheme 23) [33]. Catalyst (S,S)-68 is postulated to catalyze the reaction in a bifunctional manner: the tertiary amine deprotonates the malonate and the

• -pyran-6-carboxylate 3 using organocatalyst 4 [16]. Possible hydrogen-bonding for the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate [16]. Asymmetric desymmetrization of 4,4-cyclohexadienones using the Michael addition reaction with malonates [17]. The enantioselective synthesis of α,α-disubstituted

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• related ring-fused products, the formation of other ring sized scaffolds such as five-membered structure were much less. An interesting cascade reaction between DG-functionalized benzamides 99 and malonates 100, which enabled the synthesis of indolinones 101 via selective C–C and C–N bond construction

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• -unsaturated systems [13]. Most of the early work, including Michael’s, involved the use of stabilized or “soft” [14] nucleophiles such as malonates and nitroalkanes. Mechanistically, one can imagine a 1,2-addition of the nucleophile occurring versus the 1,4-addition if the EWG is a carbonyl compound, but this

• is not observed when malonates are used as nucleophiles. It has now been well established that “soft” nucleophiles prefer a 1,4-attack whereas “hard” nucleophiles such as organomagnesium and lithium reagents prefer a 1,2-attack. Within the past couple of decades, there has been a focus on the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• . König and coworkers showed that the same aza-Henry reaction can be catalyzed by the organic dye Eosin Y to afford the aza-Henry product 18 (Scheme 5) [67]. In addition to nitroalkanes, dialkyl malonates and malononitrile can be used as pronucleophiles to provide β-diester amine 19 and α-aminonitrile 20

• work much better using the former catalyst. Other types of pronucleophiles such as malonates are also effective in the Mannich reaction. The Rueping group extended the concept of dual catalysis by merging visible light photocatalysis with a metal-catalyzed process (Scheme 10) [77]. To make this

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeable N-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides of N-acetylcysteamine activated

• . For adding exogenous malonates to bacterial fermentations, millimolar concentrations of the SNAC-activated substrates were expected to be required in the fermentation media, making reliable and preparative-scale synthetic procedures to obtain the SNAC-ester necessary. Hence, we decided to apply a

• modular approach to our synthesis with an intrinsic transferability to variously substituted malonates. After optimization, mono-t-Bu-protected malonate provided the best starting point for the synthesis (Scheme 1) [34]. The sterically demanding protective group prevented decarboxylation during the

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• Sergei Zari Tiiu Kailas Marina Kudrjashova Mario Oeren Ivar Jarving Toomas Tamm Margus Lopp Tonis Kanger Department of Chemistry, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia 10.3762/bjoc.8.165 Abstract The organocatalytic Michael addition of malonates to symmetric

• addition of dialkylmalonates and nitromethane to 4-oxo-4-arylbutenoates catalyzed by N,N´-dioxide-Sc(OTf)3 complexes [8]. Despite these and other successful experimental results, the asymmetric addition of malonates to symmetric aromatic unsaturated 1,4-diketones has not been systematically studied

• . Products of that reaction can be used as precursors of biologically active compounds. Padmaja et al. have reported that racemic heterocyclic compounds derived from the Michael addition of malonates and malononitrile to unsaturated 1,4-diketones possess antimicrobial and antifungal properties [14][15

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• regenerated (Scheme 11). The following year, Akiyama and co-workers reported another organocatalytic asymmetric synthesis of tetrahydroquinolines using chiral phosphoric acid as the catalyst [25]. In this instance, benzylidene malonates were used as the hydride acceptor. Another important feature of this

Synthesis and mesomorphic properties of calamitic malonates and cyanoacetates tethered to 4-cyanobiphenyls

• Katharina C. Kress,
• Martin Kaller,
• Kirill V. Axenov,
• Stefan Tussetschläger and
• Sabine Laschat

Beilstein J. Org. Chem. 2012, 8, 371–378, doi:10.3762/bjoc.8.40

• with methyl 3-chloro-3-oxopropionate or cyanoacetic acid, giving liquid-crystalline linear malonates and cyanoacetates. These compounds formed monotropic nematic phases at 62 °C down to ambient temperature upon cooling from the isotropic liquid. The mesomorphic properties were investigated by

• differential scanning calorimetry, polarizing optical microscopy and X-ray diffraction (WAXS). Keywords: cyanoacetates; 4-cyanobiphenyls; liquid crystals; malonates; nematic; Introduction Nematic liquid crystals display mesophases in which the molecules are oriented along one vector defined by the director

• malonates and cyanoacetates are well known as suitable ligands for strong coordination of main-group and transition metals [25]. Benzylidene derivatives of malonic esters, so called swallow-tailed liquid crystals, were described as forming smectic phases [26]. However, most work on liquid-crystalline

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• -chloromethylene)malonates 19. The chloro alkenyl malonates 19 were synthesized in two steps from diethyl malonate and acid chlorides. The acylation of diethyl malonate was carried out with various acyl chlorides in the presence of anhydrous magnesium chloride and triethylamine, as per the reaction conditions

• developed by Rathke and Cowan [31], to give diethyl 2-acylmalonates 18. The latter were then chlorinated using phosphorus oxychloride in the presence of tri n-butylamine at reflux, by the conditions reported by Hormi [32], to give 2-(1-alkyl/aryl/heteroaryl-1-chloromethylene)malonates 19. The chloro

C-Arylation reactions catalyzed by CuO-nanoparticles under ligand free conditions

• Mazaahir Kidwai,
• Saurav Bhardwaj and
• Roona Poddar

Beilstein J. Org. Chem. 2010, 6, No. 35, doi:10.3762/bjoc.6.35

• catalysts in organic reactions [31][32][33], we now report the synthesis of 3-arylpentane-2,4-diones and diethyl 2-aryl-malonates using CuO-nanoparticles as a heterogeneous catalyst. Results and Discussion The reaction was carried out several times in order to establish the optimum ratio of reactants

• -malonates (Table 4) has been developed using CuO-nanoparticles as the catalyst. The products were obtained in moderate to good yields and the catalyst can be recycled up to four cycles with almost consistent activity. The present protocol represents a simple and remarkably active catalytic system to

Concise methods for the synthesis of chiral polyoxazolines and their application in asymmetric hydrosilylation

• Wei Jie Li,
• Zun Le Xu and
• Sheng Xiang Qiu

Beilstein J. Org. Chem. 2010, 6, No. 29, doi:10.3762/bjoc.6.29

• alkylene malonates [19]. More recently, the complex from 2,2′,6,6′-tetrakis[(4S)-phenyloxazolin-2-yl]-biphenyl and Pd(II) was reported to show excellent catalytic activities and enantioselectivities in the Wacker-type cyclization of allylphenols with up to 99% ee [20]. Despite their great application