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

• [24][25][26]. In this context, our group recently introduced an interesting asymmetric organo-cascade reaction of 2-cyanobenzaldehyde (5) with malonate 6. This resulted in enantioenriched 2-(1-oxoisoindolin-3-yl)malonate 7 which is supposed to serve as a potentially useful building block for further

• with dimethyl malonate at room temperature (Table 1). We first identified the combination of DCM and solid K2CO3 as the best-suited solvent–base system for this reaction, however etheral or aromatic solvents or aqueous (alternative) bases generally gave significantly lower selectivities (this was

• )malonate ((S)-7), according to Scheme 2. We firstly focused on two well-known mild procedures in order to avoid the classical harsh acidic conditions. Disappointingly, modifications of the Krapcho decarboxylation performed with a LiCl/H2O/DMF mixture under reflux [36][37] led to partial racemization of the

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• 10 is fed to central metabolism while the other is used in a subsequent cycle. As seen in Scheme 4, acetyl-CoA (10) is carboxylated by a bifunctional acetyl-CoA/propionyl-CoA carboxylase to malonyl-CoA (15) with HCO3− and hydrolysis of ATP. The malonate 15 is reduced to 3-hydroxypropionate (16), in

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• diallylmalonate (29) (Table 5), 93a, 93b, 93d and 93e were found more active than 85. When diethyl allyl(methallyl)malonate (77) and N,N-bis(methallyl)tosylamide (95) were used, catalysts 93a and 93b performed better than others. A full scope, involving an ene–yne reaction, was carried out with these two

• –d, Scheme 9) [84]; phophite-based complexes were thus synthesized to evaluate possible positive effects of these ligands in alkene metathesis reactions. Their stability at high temperatures allowed their use in the RCM of bis(methallyl)tosylamide (95) and diethyl bis(methallyl)malonate leading to

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• the alkaline protease from Bacillus subtilis on 7 [25]. The carboxyacetyl (malonyl) derivative of some flavonoid glycosides (i.e., 8b) and of ginsenoside Rg1 (9b) could be obtained with two-step sequences. The preliminary CAL-B catalyzed acylations of 8 with dibenzyl malonate and of 9 with bis(2,2,2

• -trichloroethyl)malonate to give the mixed malonyl derivatives 8a and 9a, respectively, were followed either by a palladium-catalyzed hydrogenolysis of the benzyl moiety to give 8b [26], or by a selective chemical removal of 2,2,2-trichloroethanol with Zn/AcOH to give 9b [27]. c) Enzymatic synthesis of symmetric

Ruthenium indenylidene “1^st generation” olefin metathesis catalysts containing triisopropyl phosphite

• Stefano Guidone,
• Fady Nahra,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2015, 11, 1520–1527, doi:10.3762/bjoc.11.166

• more active than 1 unless higher thermal stability is needed. Indeed, in the case of the malonate derivative 8, pre-catalyst 1 afforded the tri-substituted ring-closed product in 71% isolated yield. The similar structural and catalytic properties observed in the mixed phosphine/phosphite complex 1 and

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

• reported the asymmetric 1,4-addition of dibenzyl malonate to α,β-unsaturated N-acylpyrroles catalyzed by a La(OiPr)3–linked BINOL complex [220]. Optimal yields and enantioselectivies were realized by adding 1,1,1,3,3,3-hexafluoroisopropanol (HIFP) to the reaction mixture and by placing steric bulk near the

• lanthanide metal. The authors were able to achieve the asymmetric 1,4-addition of dibenzyl malonate in good yields and enantioselectivies under these conditions (Scheme 27). Lewis acid catalysts have also been used to promote asymmetric 1,4-addition of radicals to α,β-unsaturated amides. Though there were a

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• -ethoxymethylidenemalonate (1e) as an analogue of 3-oxo esters having the ester fragment instead of an acyl group. So the interaction of diester 1e with 5-AT in refluxing ethanol in the presence of catalytic amounts of triethylamine proceeded in a classical way and resulted in 2-tetrazolylaminomethylidene malonate 6 that

• malonate derivative 6. The structure of compound 10 was established by 1H and 13C NMR including 2D 1H,13C HSQC/HMBC spectra. According to the 1D NMR spectra, compound 10 has two ethoxycarbonyl groups, two phenyl moieties, two sp3-C atoms of methine group with vicinal coupling constant JH2'-H7 = 2.8 Hz, and

• days; iii: EtOH, rt, 9 days. Synthesis of pyrimidines 4a,b and 5. R= CF3 (a), (CF2)2H (b). Conditions: i: 1,4-dioxane, NaOAc, Δ, 16–18 h; ii DMF, NaOAc, 80 °C, 24–26 h; iii: 1,4-dioxane, Et3N, Δ, 40 h. Interaction of 2-ethoxymethylidene malonate 1e with 5-AT. Conditions: i: EtOH, Et3N, Δ; ii: EtOH, Δ

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

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• prepared from the corresponding glycosylazides by hydrogenation according to known procedures [19][20][21][22][23]. Next, glycosylamines 10 were condensed with tert-butyl malonate [24], N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) and triethylamine in THF to give

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

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• enantioselectivity. In a relatively successful example, the chiral aminophosphine G9 catalyzed the asymmetric double-Michael reaction between o-tosylamidophenyl malonate and 3-butyn-2-one to give the indoline derivative in 69% yield and up to 10% ee (Scheme 53). 2.15 Annulation through tandem Michael addition/Wittig

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• 2-hydroxy-2-(2-oxo-1-phenylethyl)malonate (2a) was prepared according to the reported procedure [54] and obtained as orange oil. The synthesis was carried out twice, once using L-proline (82%), once using 1 as catalyst (79%). Diethyl 2-hydroxy-2-(1-oxobutan-2-yl)malonate (2b) was prepared according

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• anions such as hydrogen phosphate and sulfate (buffered solutions), tartrate, succinate and malonate (unbuffered solutions). These anions changed the mode of photodegradation of RF and caused intramolecular photoaddition via the RF-divalent anion complex formation along with the normal photolysis

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• = 0.1033 (all data) and R1 = 0.0376 for 3207 reflections with I ≥ 2σ, GOF = 1.061. Dimethyl (Z)-2-((3-methoxy-3-oxo-1-phenylprop-1-en-1-yl)imino)malonate (4b) Compound 4b (164 mg, 54%; 61% based on consumed isoxazole) was obtained from isoxazole 1f (175 mg, 1.00 mmol), diazo ester 2c (159 + 63 mg, 1.40

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• synthetic route to prepare 1 using cheap and commercially available diethyl 2-acetamidomalonate (4) and propargyl alcohol. The desired product 1 was obtained via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and

• hydroxylation of propargylic malonate 5 without work-up of any intermediate. Keywords: alkylation; ‘click’ chemistry; ‘clickable’ polylactide; decomposition; diethyl 2-acetamidomalonate; 2-hydroxy-4-pentynoic acid; one-pot; optimization; propargyl bromide; propargyl tosylate; safe and economical; Introduction

• with low cost. Malonate has a low pKa of ~13 and can be easily deprotonated and alkylated by mild bases such as sodium/potassium alkoxides without deprotonating a terminal alkyne. Conveniently, both malonate and propargyl alcohol are commercially available in bulk quantities. Herein, we report one

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• over six months under ambient atmosphere. To test the suitability of these 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands in Pd-catalyzed allylic alkylation reactions, we began our study by choosing methyl cinnamyl carbonate and dimethyl malonate as the model substrates, along with

• Pd-catalyzed allylic alkylation of cinnamyl carbonate with dimethyl malonate afforded the linear product as the major product (b/l: 40/60). Whereas the corresponding ligand L1d with two CF3 groups (instead of two phenyl groups) at the P atom improved the regioselectivity significantly (b/l: 96/4). A

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

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• with malonate and another methylmalonate (including deoxygenation steps) seemed to be plausible [16]. These biogenetic considerations excluded methyl groups at positions 9 and 11. To prepare a mixture of all stereoisomers of 14, we again used 2 as the starting material (Figure 2). Monobenzylation to 9

• ]. Location at position 2 would provide 14, which was already ruled out. According to a conceivable biosynthesis of the natural product from methylmalonate and acetate, positions 3 and 5 would be less favourable [16]. However, linear condensation of five methylmalonate units and a final malonate (and again

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• malonate anion. Tandem hydrophosphinylation/Michael/Michael reaction of allenyl-H-phosphinates. 5-Membered “cyclo-PALA” via intramolecular Mitsunobu reaction. 6-Membered “cyclo-PALA” via intramolecular Mitsunobu reaction. Intramolecular Kabachnik–Fields reaction. Tandem Kabachnik–Fields/alkylation reaction

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• to the activated C=C double bond of malonate 38 followed by hydrolysis and decarboxylation to generate adduct 39 in two steps (Scheme 10). Conclusion In conclusion, we have presented a variety of approaches to novel fluorinated (1-aminoalkyl)phosphinic acids starting from the appropriate fluorinated

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• investigation commenced with the preparation of 1-(6-chloropyrimidin-4-yl)hydrazines 3. The required starting 4,6-dihydroxypyrimidines 1 can be prepared following the reported procedure by condensation of dimethyl malonate either with formamide (for 1a) or the respective formamidine salts (for 1b and 1c) [15

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

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• equiv), EtOH, reflux; (b) monoethyl malonate (1.1 equiv), DCC (1.1 equiv), CH2Cl2, rt; (c) NaOMe (1.1 equiv), benzene, EtOH, reflux; (d) RNH2 (1.0 equiv), toluene, reflux. Synthesis of N-alkyl 3-carboxamide tetramic acid. Reaction conditions: (a) 1. glycine methyl ester∙HCl (1.0 equiv), Et3N (1.2 equiv