Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• -nitrobenzyl)malonate upon treatment with sodium hydroxide undergoes a multistep transformation resulting in 11-hydroxyindolo[3,2-b]quinoline-5-N-oxide (a) [9]. This approach is based on the first synthesis of the indolo[3,2-b]quinoline framework by Fichter and Boehringer in 1906 [10]. Indoxyl [11] and N,O

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• ), C12–O3 1.3386(18), C11–C12 1.3687(19), C11–C14 1.450(2) Å) clearly indicate the enolic form of the compound. The reaction of 1 with less acidic diethyl malonate required the addition of 1 equivalent of Et3N. In this case product 13 was isolated in 78% yield (Table 1, entry 8). Again, due to the

• without added base while in case of diethyl malonate (pKa(H2O) 13.3) and TNT (pKa(H2O) 13.6) the addition of one equivalent of Et3N is required. In the latter case the formation of the adducts proceeds through the attack of the anion on C7. All other CH acids used exist mainly in enol form in polar

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• )malonate (24) to yield a mixture of two cyclic CF3 products, the main one being deprived of the chlorine atom (Scheme 20). Unfortunately, no more investigation was carried out on this type of cascade reactions. Trifluoromethylchlorosulfonylation of alkenes: It was previously evocated that the system

• example of such type of reaction was reported by Just and Hakimelahi in 1979 [49]. Their work was focused on the mono- or dichlorination of various carbon acids, in the pKa range between dialkyl malonate and methyl dichloroacetate, as well as certain nucleophiles, were reacted with

• the isolation of similar compounds starting from differently substituted β-lactams, notably carrying a malonate moiety linked to the nitrogen [57]. More recently, CF3SO2Cl also found to be an appropriate reagent for the asymmetric introduction of a chlorine atom onto several substrates. For instance

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• three water molecules which are released into bulk water upon mannose binding and thereby contribute to a favorable entropic effect. The cost to remove one water molecule from a calcium–malonate model system was calculated quantum mechanically (QM) to be 56.9 kJ/mol by Charifson et al. [64]. This is in

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

• proposed strategy of bicyclo[3.2.1]octanone 14 assembly is based on a combination of ring closing metathesis reaction and intramolecular addition of the malonate anion to a nitrosoalkene unit (Scheme 6). On the first stage, readily available chlorodiene 9 was subjected to a metathesis reaction with the

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• efforts had to be invested, before acid 21 could be efficiently obtained as shown in Scheme 4. Finally, after optimization of a reported procedure [73] the successful route employed a one-pot process involving a sodium hydride-mediated coupling of methyl malonate 19 with iodoform (20) followed by a

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -indanone [37]. In this synthesis, a mixture of diethyl 2-(3,5-dimethoxybenzyl)malonate and methanesulfonic acid was stirred at 100 °C for 2 h and 5,7-dimethoxy-1-indanone was obtained in excellent yield (95%). A new route for the synthesis of an anticancer agent, benzopyronaphthoquinone 51 from the

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• intriguing feature of this molecule is the highly oxygenated carbon chain in which eight hydroxy groups, one of which is used for lactone formation, are contiguously aligned. A 1,3-diol is a common structural element in aliphatic polyketides because the incorporation of malonate-precursors gives rise to the

• pathway [22]. In this study, biosynthetic precursors of 1 were investigated for further genetic and enzymatic studies. Results and Discussion It was obvious from its structure that 1 was synthesized through the malonate pathway. First, [1,2-13C2]acetate was fed to the culture to ensure the alignment of

• malonate units. In the 13C NMR spectrum, split signals arising from 13C–13C couplings were observed for six pairs of carbons: C-11/C-12, C-13/C-14, C-15/C-16, C-17/C-18, C-19/C-20, and C-21/C-22 (Table 1, Figure S1 in Supporting Information File 1). In the 2D-INADEQUATE spectrum of 13C-labeled 1 obtained

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

• solution in the range of 5–10 °C with a coolant of −25 °C. The further work-up follows the procedure given for the hetero-coupling reaction. General procedure for the preparation of the menthol esters: To a solution of 4.3 mmol of monobenzyl malonate 5 or 6 in 20 mL dry methylene chloride 0.8 mL thionyl

Supramolecular frameworks based on [60]fullerene hexakisadducts

• Andreas Kraft,
• Johannes Stangl,
• Ana-Maria Krause,
• Klaus Müller-Buschbaum and
• Florian Beuerle

Beilstein J. Org. Chem. 2017, 13, 1–9, doi:10.3762/bjoc.13.1

• , Germany 10.3762/bjoc.13.1 Abstract [60]Fullerene hexakisadducts possessing 12 carboxylic acid side chains form crystalline hydrogen-bonding frameworks in the solid state. Depending on the length of the linker between the reactive sites and the malonate units, the distance of the [60]fullerene nodes and

• crystallization of C3 and also synthesized the next homologue C4 starting from malonate 1 [59] according to a standard two-step protocol via a sixfold Bingel reaction followed by acidic deprotection (Scheme 1). As we observed the insertion of MeOH molecules into the hydrogen-bonding network of HFF-1 [57], we also

• are cross-linked by hydrogen bonding. Thereby, six of the twelve side arms form linear COOH dimers (four intralayer and two interlayer) and two carboxylic acids are bound to malonate ester groups from adjacent layers (see Figure S10 in Supporting Information File 1). The remaining four carboxylic acid

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

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• ], or malonate diesters via Claisen condensations followed by hydrolysis and decarboxylation. The greenest routes appear in the [4 + 2] strategy. The three-step route beginning with photochemical ring opening of cyclobutenone to give vinylketene, followed by Diels–Alder addition to ethylene leading to

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

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