Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• stereoablative approach (Scheme 3) [22][23]. Deprotonation and elimination of the halide in oxindole (±)-8 leads to achiral azaxylylene intermediate 11, which is trapped with malonate nucleophiles to form all-carbon quaternary centers. The overall transformation is unusual since oxindoles are typically

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ) (rhiPKS) and synthetic SNAC-thioesters revealed that the chain branch originates from a syn-selective Michael addition of an ACP-bound malonate unit 133 to a KS-bound α,β-unsaturated thioester 132 (Scheme 20b) [130]. This results in an intermediate 134 in which the ACP and the KS domain are covalently

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

• chiral calcium alkoxide complex was generated in situ by mixing Ca(OEt)2, PyBox ligand (S,S)-88, and phenol 89. The authors found that the slow addition of malonate 86 and the use of phenol 89 and ethanol as additives were all crucial for achieving high yield and enantioselectivity, although the exact

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• standard test reaction of (E)-1,3-diphenylallylacetate with dimethyl malonate as nucleophile (Scheme 8). The two catalysts derived from ligand 14 with a free hydroxy group and the corresponding triethylsilyl-protected derivative both performed well affording enantioselectivities of 90% and 98% ee

Separation and identification of indene–C₇₀ bisadduct isomers

• Bolong Zhang,
• Jegadesan Subbiah,
• David J. Jones and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2016, 12, 903–911, doi:10.3762/bjoc.12.88

• ] and C70 bis-malonate isomers [17], was expected to provide further information on adduct configurations. The UV–vis spectra of fractions 1, 2 and 3 showed very similar spectral features when compared with the spectrum of the 5 o’clock isomer of C70 bis-malonate, suggesting that they are all 5 o’clock

• to the 12 o’clock C70 bis-malonate (Figure 6c). Thus the eight major regioisomers of IC70BA were identified. However, the remaining fractions 5–8, were also confirmed to be IC70BA isomers by mass spectrometry. Since the UV–vis spectrum of these fractions did not correlate to those of the known α

• bisadducts: a) fraction 1, 2, 3 and 5 o`clock bis-malonate [17]; b) fraction 4, 9-1 and 2 o`clock-B of IC70BA [9]; c) fraction 10, 11 and 12 o`clock bis-malonate [17]. Schematic diagram of the architecture of BHJ solar cell devices (a) and J−V curves of the devices containing P3HT and each IC70BA fractions

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

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• elongated by a butyrate moiety. Subsequently three further elongation steps, this time using malonate as extender units, follow. This results in the incorporation of acetate units via Claisen-condensation reactions. The reductive domains, i.e., ketoreductase (KR) and dehydration (DH) domains, present in the

• formation for the ajudazols A and B in Chondromyces crocatus Cm c5 [80]. 2.2 Biosynthesis by PKSII systems In the type II PKS-catalyzed biosynthesis, the subunit type of such megaenzyme systems, the starter molecule and the extender units, mostly malonate molecules, are assembled at the same ACP. A

• encoded by a set of genes architecturally similar to most other type II PKS clusters. EncA represents the KSα, EncB the KSβ, and EncC the ACP domain. First, an uncommon benzoate starter unit gets elongated by seven malonate molecules. This nascent carbon chain undergoes a rare Favorskii-like rearrangement

(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

• ethyl malonate, producing the active nucleophile, while the thiourea group activates the electrophile (Scheme 6). The above catalytic reaction provided products with yields up to 99%, dr up to 93:7 and ee up to 93%. Carter and co-worker utilized a similar primary amine-thiourea, organocatalyst 11, in an

• 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

• , Xu and co-workers described a three-compound reaction between dialkyl malonate 222, nitro-alkene 82 and substituted enal 154, catalyzed by the chiral quinine-derived thiourea 57 and organocatalyst 223, affording product 224 with a substituted cyclohexane-ring core (Scheme 70) [89]. The experimental

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• -additions that have been facilitated by CPD and CPN derived catalysts. For example, and amongst the earliest examples in the field, underivatized CPD or CPN were used in the addition of dimethyl malonate (40) to a range of nitrostyrenes 41, giving the resulting adducts with excellent enantioselectivity

• . A cupreidine derived catalyst induces a dynamic kinetic asymmetric transformation. Cupreine derivative 38 has been used in an organocatalytic asymmetric Friedel–Crafts reaction. Examples of 6’-OH cinchona alkaloid catalyzed processes include: (a) Deng’s addition of dimethyl malonate into

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• chiral ligands in palladium-catalyzed allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate. The D-fructo-PyOx ligand provided mainly the (R)-enantiomer while the D-psico-configurated ligand gave the (S)-enantiomer with a lower enantiomeric excess. Keywords: asymmetric catalysis

• benchmark test for selectivity, the palladium-catalyzed asymmetric addition of dimethyl malonate to 1,3-diphenylallyl acetate was often used in the literature for testing the scope of carbohydrate derived ligands for this purpose [9][10][11][12][13]. For instance, Kunz and Gläser have demonstrated the

• -dipolar cycloaddition of 2,6-pyridinedicarbonitrile N,N-dioxide to acetyl protected exo-glucal. The performance of ligand A in asymmetric catalysis was then tested in the palladium-catalyzed allylic addition of dimethyl malonate to 1,3-diphenylallyl acetate which, however, afforded the desired allylic

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

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