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

• Stabilized enolates and their equivalents are the most studied C-nucleophiles in Michael addition reactions with nitrosoalkenes. A first systematic study in this area was done by Ohno and co-authors [13][23], who reported the addition of diethyl malonate and acetylacetone anions to cyclic nitrosoalkenes

• NSA1a–c generated from the corresponding α-chloroketones (2-chlorocyclohexanone oxime (1a), 2-chlorocyclooctanone oxime (1b) and 12-chloro-сyclododeca-4,8-dien-1-one oxime (1c)) upon the action of an excess of nucleophile (Scheme 2). It was found that oximes 1b and 1c react both with diethyl malonate

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• obtained in quantitative yield as a clean product with no need for purification. We also investigated the continuous-flow reduction of nitro ester 5, which can be conveniently prepared in one step through the organocatalyzed addition of diethyl malonate to trans-β-nitrostyrene promoted by a chiral thiourea

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• further used as synthetic intermediates in numerous synthetic routes to heterocyclic compounds and molecules of biological interest [41][42]. Results and Discussion We first investigated the allylation of diethyl malonate (2a) with the allylic alcohol 1a in DMF in the presence of Pd(OAc)2 (10 mol %), PPh3

• , carried out in DMF at 80 °C, gave a better result (30% yield in 12 h), using, in addition to NaH (0.5 equiv), 1 equiv of Et3B (Table 1, entry 3). Moreover, a remarkable improvement in yield (60% in 6 h) was also observed for the allylation of diethyl malonate (2a) with the MBH alcohol 1a using an excess

• of Et3B (3 equiv) and 1 equiv of NaH (Table 1, entry 4). Mechanistic considerations Scheme 1 illustrates the most probable catalytic cycle for the allylation of diethyl malonate (2a) with allyl alcohol 1a. We assume that there is first an activation of 1a through its conversion into I1 using Et3B [29

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

• first tested in the reaction of trans-nitrostyrene (1a) with diethyl malonate (2a), leading to the enantioenriched addition product 4aa with a single stereocenter. In order to the creation of two tertiary-quaternary contiguous stereocenters (5aa) we also used ethyl 2-oxocyclopentanecarboxylate (3a) as

• of nucleophile and 10 mol % of catalysts (entries 1–4 and 9–11 in Table 1). As a general trend, the reactions were faster, and much more stereoselective for ketoester 3a than for diethyl malonate 2a, and that the difference was specially remarkable when supported ethylenediamine-derived thioureas II

• next consider the reaction of some 4-substituted nitrostyrenes (1b–d) with diethyl malonate (2a), and the addition of a range of β-functionalized nucleophiles 2b–g to 1a promoted by supported catalysts IV (5 mol %) and V (2 mol %), respectively (Scheme 2 and Table 2). The results obtained in the

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• -trimethylphenol analogously to the procedure described for 2,2,5,8-tetramethyl-6-chromanol by Dean [27]. 2,3-Dihydroxy-1,4-dioxane was obtain according to Venuti [37]. Substrates for testing catalysts in RCM reactions were prepared by allylation of commercial diethyl malonate with allyl bromide and/or 3-chloro-2

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

• demonstrated an interesting strategy to assemble [3.4]cyclophane derivative 197 by using the SM cross coupling and an RCM as key steps. The commercially available active methylene compound diethyl malonate was alkylated with a benzyl bromide derivative followed by the SM cross coupling to give dialkyl 196

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• methylene deprotonation, the alkoxide anion (RO−), can in fact originate (in situ) from the degradation of the allylic carbonate by the Pd catalyst [2]. Optimisation of the reaction conditions was carried out on the model substrate diethyl malonate by varying several parameters such as ligands, Pd sources

• times) was found to depend on the nucleophilic strength of the intermediate enolates, and ultimately on pKa values (reactivity scale: diethyl malonate pKa 13.5 > acetoacetate pKa 11.0 > acetylacetone pKa 8.9). As an example, diethyl malonate reacted with allyl methyl carbonate much faster than

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

• nucleophile, and the electrophile. In 1883, Komnenos reported the first conjugate addition where he added the diethyl malonate anion to ethylidene malonate [12]. This reaction was not fully investigated until 1887, when Michael thoroughly studied this reaction using various stabilized nucleophiles and α,β

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• side-reactions of the malonyl radical and diethyl malonate. We explored alternative alkyl halide oxidants that would form inert byproducts. No reaction was observed when substituting BrCCl3 with ClCH2CN (−0.72 V vs SCE [48]) but to our delight, BrCH2CN (−0.60 V vs SCE [48]) resulted in near

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• [11] in presence of K2CO3 and triethylamine in DMF at 70 °C, or with activated alkenes, such as acrylates, acrylonitrile or diethyl malonate, in presence of triethylamine and an oxidant in DMF at 90 °C, led only to the normal cycloaddition products, i.e., pyrrolo[1,2-a]benzimidazoles [12]. When the

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• N-aryl-3-hydroxyisoindolinones with diethyl malonate and subsequent hydrolysis, decarboxylation and Friedel–Crafts acylation sequence also result in the formation of isoindolo[2,1-a]quinolones [16][17]. N-aryl-3-hydroxyisoindolinones with an aptly positioned alkene moiety at the ortho position of

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

• Ashley N. Jarvis,
• Andrew B. McLaren,
• Helen M. I. Osborn and
• Joseph Sweeney

Beilstein J. Org. Chem. 2013, 9, 852–859, doi:10.3762/bjoc.9.98

• with ethyl acetate/light petroleum (1:1) as an eluent. Palladium-catalyzed ring-opening with malonate: To diethyl malonate (typically 0.3–0.6 mmol, 1.1 equiv) in THF (1.5 mL), at room temperature, under argon, was added sodium hydride (1.1 equiv), and the colourless solution was left to stir for 30 min

Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides

• Andrew Tigchelaar and
• William Tam

Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201

• %), respectively. Synthesis of substrate 1g commenced with deprotonation of diethyl malonate, followed by addition of mesylate 12, and subsequent deprotonation and addition of propargyl bromide as described by Gilbertson [31] to provide dieneyne 13 (Scheme 4). Diene 13 was then treated under the standard

Influence of cyclodextrin on the solubility of a classically prepared 2-vinylcyclopropane macromonomer in aqueous solution

• Helmut Ritter,
• Jia Cheng and
• Monir Tabatabai

Beilstein J. Org. Chem. 2012, 8, 1528–1535, doi:10.3762/bjoc.8.173

• (4) was synthesized following a procedure described in [32]. Diethyl 2-vinyl-1,1-cyclopropanedicarboxylate could be obtained according to [33] from sodium ethoxide, diethyl malonate and trans-1,4-dichloro-2-butene in ethanol (Scheme 2). The desired macromonomer 5 was prepared in two steps according

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• Organic Chemistry I, University of Erlangen-Nuremberg, Henkestraße 42, 91054, Erlangen, Germany 10.3762/bjoc.8.168 Abstract A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene

• of diethyl malonate (14) to nitrostyrene (11) and to find a plausible explanation as to why the enantioselectivity of this reaction is low. As a first step, we explored the conformational flexibility of the catalyst 7 itself. Pápai and co-workers [57] studied a similar dimethylaminothiourea catalyst

• . Conclusion In summary, we have demonstrated that the new guanidine derived chiral thiourea 7 can catalyse the asymmetric nitro-Michael addition of diethyl malonate with trans-β-nitrostyrene, giving high yields (up to 96%) but low enantioselectivities. Based on extensive computational studies, the low

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

• catalysts were screened in the reaction of phenyl disubstituted unsaturated 1,4-diketone 1a with diethyl malonate (2a, Table 1). The reaction was run in DCE at room temperature in the presence of 10 mol % of catalyst with a five-fold excess of malonate. In all cases, the yields of the products were very

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• processes and chemotypes [5]. For example, we have conducted multidimensional reaction screens using alkynyl o-benzaldehyde scaffolds, which revealed a number of reactions affording novel polycyclic scaffolds, including Au(III)-catalyzed addition of diethyl malonate to 1 to afford isochromene 2 (Scheme 1

• , evaluating a number of metal catalysts in the presence of diethyl malonate. From this focused reaction screen we identified three types of reactivity: (1) no reaction; (2) alkyne hydration (4); and (3) cycloisomerization leading to isochromene (5) (Figure 1). Many catalysts resulted in no reaction, including

Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities

• Hany M. Mohamed,
• Ashraf H. F. Abd EL-Wahab,
• Ahmed M. EL-Agrody,
• Ahmed H. Bedair,
• Fathy A. Eid,
• Mostafa M. Khafagy and
• Kamal A. Abd-EL-Rehem

Beilstein J. Org. Chem. 2011, 7, 1688–1696, doi:10.3762/bjoc.7.199

• -diiodosalicylaldehyde; diethyl malonate; ethyl cyanoacetate; coumarins; Michael reaction; Introduction Coumarins and their derivatives are biologically and pharmaceutically interesting compounds known for their use as additives in food, perfumes, cosmetics, pharmaceuticals, platelet aggregation and agrochemicals [1][2

• diiodocoumarin derivatives bearing side chains with different structures, as such derivatives could possess interesting and useful biological properties. Results and Discussion Interaction of 3,5-diiodosalicylaldehyde with diethyl malonate according to the literature procedure [14][15] afforded ethyl 6,8

• diethyl malonate according to the literature procedures [19][20][21]. 6,8-Diiodocoumarin-3-carboxylic acid (2). A solution of compound 1 (0.47 g, 10 mmol) in absolute ethanol (20 mL) was mixed with ethanolic solution of KOH (10%), which was then refluxed for 10 min. The reaction mixture was poured onto

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

• the aryl substituents with the electron donating group. The presence of the electron withdrawing group on the aryl ring at the α-carbon of vinylaziridines reduces the electron density on the methylene carbon of diethyl malonate and thus reduces the rate of iodo group displacement (Table 2, entries 5

• conditions: i) THF, rt, 3 h; ii) NaI, acetone, rt, overnight. Reaction conditions: i) THF, TEA, rt; ii) NaI, acetone, rt, overnight. Synthesis of N-vinylaziridines from diethyl malonate and acyl chlorides. Iodide ion mediated ring expansion of N-vinylaziridines. Supporting Information Supporting Information

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

• . The above results encouraged us to investigate further reactions. Under similar reaction conditions, diethyl malonate was treated with iodobenzene to give the desired product in 78% yield (Scheme 3). The reaction was then repeated with a variety of aryl halides. The results are summarized in Table 4

• acetylacetone using different aryl halidesa C-arylation of diethyl malonate using different aryl halidesa. Recycle studies of nano-CuO for C-arylation reactiona. Supporting Information Supporting Information File 74: Typical procedure and characterization data of prepared compounds Acknowledgements Saurav