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

• , which may possibly allow additional interactions with the aromatic substrates 1, the catalyst IX was also chosen. Scope of the reaction Next, we studied the effect of the malonate structure on the stereoselectivity of the reaction (Table 2). Although, the ester moiety can be replaced by other functional

• groups in the course of further synthetic transformations its main role is to provide the addition products with high ee value. The conditions for the reaction remained the same as they were in the catalyst screening experiments, except that a smaller excess of malonate (3 equiv, unless stated otherwise

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

• diynyl benzaldehyde 3 and dimethyl malonate is catalyzed by Cu(I) to afford isochromene 24 [20][21][22]. Pt(II) π-coordination of the pendant alkyne of 24 followed by cyclization of the enol ether affords the seven-membered-ring metal-“ate” intermediate 25. The cyclization occurs at the face opposite the

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• also tested in the Michael addition of methyl malonate to trans-β-nitrostyrene (Table 4) [21]. The catalyst gave quantitative yield and excellent enantioselectivity after 3–4 days reaction time. However, the catalyst exhibited poor recycling properties as yields fell sharply after the second reaction

• determined by HPLC analysis (Chiralpak AD-H, 2% iPrOH in isohexane, 1.0 mL/min): tR = 19.2 min and 26.2 min. General procedure for asymmetric Michael addition of methyl malonate to trans-β-nitrostyrene: trans-β-Nitrostyrene (83.4 mg, 0.56 mmol) and methyl malonate (0.23 g, 1.78 mmol) were dissolved in

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• CoA as a starter unit, modular and iterative assembly of malonate extender units produces a linear tetraketide intermediate capable of being folded in at least two ways [5]. Intramolecular Claisen condensation and subsequent enolization produce phloracetophenone (path A), while aldol condensation

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• by following literature procedures [22][23][24][25]. In the first step from bis(hydroxymethyl)malonate 38, simple nucleophilic substitution is coupled with an ester hydrolysis and a debrominative decarboxylation. Another nucleophilic substitution with thioacetate converted bromide 39 into thioester

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• and one of 2-methylbutanol. Similarly, iso-leucine (its involvement in biosynthesis being supported by the presence of esters of 2-methylbutanol) will give rise to anteiso-branching. However, due to the general principles of chain elongation with acetate/malonate units, in X. c. pv. vesicatoria 85-10

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

• described in the literature [33][34]. Therefore, we decided to explore the synthesis and mesomorphic properties of malonates and cyanoacetates 5 tethered to calamitic 4-cyanobiphenyl units (Scheme 2). Results and Discussion The syntheses of malonate and cyanoacetate derivatives 11, 13 are shown in Scheme 3

• C6- or C10-spacers, in 68% and 60% yield, respectively [36][37][38] after recrystallization from methanol (Scheme 3). The malonate unit was attached by treatment of the compounds 9a,b with methyl 3-chloro-3-oxopropionate (10) in the presence of pyridine in CH2Cl2 to yield the malonates 11a,b in 57

• ,b were isolated as colourless solids in 59% and 41% yield. The obtained malonate and cyanoacetic esters 11a,b and 13a,b were subjected to differential scanning calorimetry (DSC) studies (Figure 1, Figure 2, and Table 1). During the first heating runs all compounds did not show the appearance of any

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• the commercially available substituted malonate 9 gave product 10 together with diethyl cyclobutanedicarboxylate (formed by cyclization of the malonate anion onto the internal alkyl chloride). This by-product was removed by column chromatography after reduction of both esters to give diol 11. Mono

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

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• polysubstituted C–vinyl butyrolactones through a gold-catalyzed highly diastereoselective cyclization of malonate substituted allylic acetates [49]. As an example, treatment of syn-4-acetoxycyclohexenyl malonate 92 with a catalytic amount of AuPPh3Cl/AgSbF6 in DCE at 70 °C for 3 h led to the isolation of 3,4-anti

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

• derivative in 88% isolated yield (Scheme 5). Similarly, chloro displacement in β-chloro alkenyl malonate 19e with 2-butylaziridine (30) gave 2-substituted N-vinylaziridine derivative 31, which upon iodide ion mediated aziridine ring expansion gave the 2,5-disubstituted pyrroline derivative 32 in 82% isolated

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• malonate diesters, while tetrahydropyrans 3c and 3d were obtained from tetrahydro-4H-pyran-4-one. The advantages and disadvantages of each route are discussed. Dibromides 1c and 1d were used to prepare sulfonium zwitterions 11c and 11d. Keywords: 1,5-dibromopentanes; heterocycles; methodology; synthesis

• steps starting from alkylation of malonate diester followed by reduction of the esters, tosylation of the alcohols, carbon homologation with NaCN, hydrolysis of the cyano groups to carboxylic acids, and lastly a second reduction to VII. Overall yields of diols VII using Method 1A are around 10% [27][28

• ]. The second route (Method 1B) consists of a Knoevenagel condensation of malonate diester and an aldehyde followed by conjugate addition of a second equivalent of malonate diester. The tetraester is hydrolyzed, decarboxylated, esterified, and then reduced to give the diol. Yields for tetraesters are in

New library of aminosulfonyl-tagged Hoveyda–Grubbs type complexes: Synthesis, kinetic studies and activity in olefin metathesis transformations

• Etienne Borré,
• Frederic Caijo,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2010, 6, 1159–1166, doi:10.3762/bjoc.6.132

• Procedure for the kinetic reaction: A NMR tube equipped with a septum was filled with diethylallylmethallyl malonate (8) (25 mg, 0.1 mmol) and CD2Cl2 (900 μL) under an argon atmosphere. The sample was equilibrated at 30 °C in the NMR probe. The sample was locked and shimmed before the catalyst addition (100

About the activity and selectivity of less well-known metathesis catalysts during ADMET polymerizations

• Hatice Mutlu,
• Lucas Montero de Espinosa,
• Oĝuz Türünç and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2010, 6, 1149–1158, doi:10.3762/bjoc.6.131

• C1 to challenging substrates, such as diethyl di(methallyl)malonate in fluorinated aromatic hydrocarbon solvents, resulted in a remarkable enhancement of catalytic activity. Moreover, this approach was successfully extended to the RCM of natural products and the cross-metathesis formation of

Light-induced olefin metathesis

• Yuval Vidavsky and
• N. Gabriel Lemcoff

Beilstein J. Org. Chem. 2010, 6, 1106–1119, doi:10.3762/bjoc.6.127

• active counterpart (trans-dichloro). Thus, illumination with UV light generates an active isomer, but a short heating period regenerates the inactive isomer. The switchable nature of the system was demonstrated by 15 min irradiation of a tetrachloroethane solution of diethyldiallyl malonate with 5 mol

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

• . Synthesis of 3-phenylpentane-2,4-dione using CuO-nanoparticles. Synthesis of diethyl 2-aryl-malonate using CuO-nanoparticles. C-arylation reaction catalyzed by different Cu catalystsa. CuO-nanoparticles catalyzed coupling reaction of acetylacetone and iodobenzene in various solventsa. C-arylation of

• 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

An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

• Rajeshwar Reddy Sagyam,
• Ravinder Buchikonda,
• Jaya Prakash Pitta,
• Himabindu Vurimidi,
• Pratap Reddy Padi and
• Mahesh Reddy Ghanta

Beilstein J. Org. Chem. 2009, 5, No. 66, doi:10.3762/bjoc.5.66

• condensation reactions, such as the condensation of oxazolo[3,2-b]pyridazinium perchlorates with malononitrile, ethyl cyanoacetate and ethyl malonate in the presence of sodium ethoxide [15]; the condensation of 1,4,7-triketones with hydrazine followed by dehydrogenation [16]; the condensation of cyanoacetic

Catalytic synthesis of (E)-α,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene

• Rubén Manzano,
• Lidia Ozores,
• Andreas Job,
• Lars Rodefeld and
• Benjamin List

Beilstein J. Org. Chem. 2009, 5, No. 3, doi:10.3762/bjoc.5.3

• satisfactory with respect to the demand for atom economy is still needed [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. We have recently developed a new approach based on the Knoevenagel condensation of readily available and inexpensive malonate half esters with aldehydes which

A superior P-H phosphonite: Asymmetric allylic substitutions with fenchol- based palladium catalysts

• Bernd Goldfuss,
• Thomas Löschmann,
• Tina Kop-Weiershausen,
• Jörg Neudörfl and
• Frank Rominger

Beilstein J. Org. Chem. 2006, 2, No. 7, doi:10.1186/1860-5397-2-7

• Pamies et al. (Scheme 2) [7]. Besides bidentate P, N-ligands, monodentate ligands are useful, as was demonstrated successfully by Hayashi et al. with the MeO-MOP ligand, yielding 90% branched product with 87% ee for a C-methylated malonate nucleophile and the 4-methoxyphenylallyl substrate [8]. Van

• shorter C1-Pd bond distances (2.13 Å, 2.08 Å and 2.13 Å, cf. Figure 1, Figure 2 and Figure 3). This differentiation agrees with the "trans to phosphorus" rule, [1][29][30] which predicts the attack of the nucleophile (i.e. malonate) at the weakest (longest) C3-Pd bond, yielding preferably the chiral

• , branched product. Monodentate BIFOP ligands yield more of the linear alkylation product (Table 1), despite their huge steric demand. Surprisingly, the chloro- and bromophosphites, BIFOP-Cl and BIFOP-Br, are stable ligands under these reaction conditions: no conversion with nucleophiles (e.g. malonate), as