One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

•  2). Scheme 2 also shows the physical state descriptors and photographs of the practical experiment. With suitable conditions in hand, the scope of this one-pot mechanochemical process was explored (Scheme 3). Initially, the scope of β-ketoesters was assessed and the procedure was found to be

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• conditions to effect catalytic processes with sub-stoichiometric quantities of iodine compound in the presence of an oxidant [6][7][8][9][10][11]. In this regard, we have reported the use of iodoarenes as precatalysts in the cyclizations of N-alkenylamides 1 [12], δ-alkynyl β-ketoesters 2 [13] and 5-oxo-5

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• nucleophiles dates back to 2002, when Kim and Park described the first use of cinchona alkaloid-based quaternary ammonium salts A (i.e., derivative A1) for the enantioselective α-fluorination of β-ketoesters 1 by using N-fluorobenzenesulfonimide (NFSI, 2) as the fluoride-transfer reagent [73] (Scheme 2). By

• described the first highly enantioselective protocol for this reaction [74]. By using just 2 mol % of their trademark binaphthyl-based PTCs B, they were able to access a broad variety of differently functionalized α-fluoro-β-ketoesters 3 with excellent selectivities and in almost quantitative isolated

• substitution of the C9–OH group of the cinchona skeleton by fluorine has a pronounced effect on the conformation of these catalysts and that ammonium salt C can then be successfully used for the aforementioned asymmetric α-fluorination of ketoesters 1 [75]. A significant improvement for the use of classical

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• evaluated as chiral organocatalysts in the enantioselective α-chlorination of β-ketoesters, with excellent results obtained after optimisation of the organocatalyst structure [12]. In an effort to identify new, easily accessible and tuneable organocatalysts with the privileged pyrrolidine motif from the

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

• ketoesters 59. The base-mediated cyclization of the latter in the presence of sodium ethoxide led to the formation of the corresponding 1-indanone anions α to carbonyl, which next were alkylated to give 2-substituted 1-indanones 60 (Scheme 20). This one-pot process utilizing a multi-task palladium catalyst

• vinyl β-ketoesters 156 in the presence of AlCl3 as a promoter, in high yields (up to 99%) (Scheme 45). It was further proved that the pattern of substituents at C-2, C-4 and C-5 positions was essential for the reaction efficiency. 1.2 From alcohols An interesting synthesis of optically active 1

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• compounds 11a–e were washed with acetonitrile (1 × 1 mL). The reactions done with non-symmetric dinucleophiles 8b, 8e, and 8f furnished isomeric product mixtures. Data obtained from DFT-B3LYP theoretical calculations showed that in the three α-ketoesters 5–7, the carbonyl of the ketone has a larger LUMO

• -ketoesters 5 and 6 were done with amidines 8g,h. The reaction between 5 and 8g was tested to achieve the optimal conditions. The use of acetonitrile or ethanol as the solvent (at 25 °C or reflux) in the presence of bases such as potassium carbonate (K2CO3) or sodium ethoxide (CH3CH2ONa), and with reaction

• condensation reaction between the α-ketoester fragment in polyazaheterocycles and amidines. The experimental results and theoretical calculations of HOMO/LUMO coefficients, together with charge density and energetic stability of the intermediates, indicate that reactions between α-ketoesters and dinucleophiles

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

• kinetic resolution (DKR) [10][11][12][13][14][15][16]. Processes of this type were first described by Noyori in the enantioselective hydrogenation of β-ketoesters ((±)-1 → 2, Scheme 1) [6]. In the event, the resident stereocenter of the substrate 1 can epimerize via tautomerization to the enol form

• reaction was reported by Stoltz for the generation of enantioenriched all-carbon quaternary stereocenters from racemic allyl β-ketoesters (e.g., (±)-20 → (+)-23, Scheme 5) [29]. This particular reaction is especially unusual since the stereoablative step requires scission of a C–C bond at a quaternary

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• , Scheme 1) in polycarbonate chemistry [4][5], and TiO2/SiO2 and similar binary combinations are applied in the transesterification of β-ketoesters [6], and in the synthesis of unsymmetrical carbonates R1OC(O)OR2 [7]. Superacidic solids have also been described as transesterification catalysts and a

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• Jakub Saadi Christoph Bentz Kai Redies Dieter Lentz Reinhold Zimmer Hans-Ulrich Reissig Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, Germany 10.3762/bjoc.12.118 Abstract Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium

• forming reactions of aryl halides that involve an insertion of the intermediate aryl palladium species into a carbonyl group are relatively rare (see discussion below). Therefore this serendipitous discovery led us to investigate the reaction in more detail. Results The required γ-ketoesters A bearing the

• in Schemes 4–6. Surprisingly, the presence of excess of the base triethylamine and the fairly long reaction times do not lead to noticeable epimerization of the precursor γ-ketoesters that would lead to an erosion of the observed stereoselectivity. In all examples the methoxycarbonyl group and the

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• substrate; however, to date, the carbonyl components for these reactions are mostly restricted to 1,3-diones, β-ketoesters, malonates, α-cyanoacetates, 3-substitued oxindoles and related systems. Generally, enolizable esters or carboxylic acid derivatives have been challenging in this strategy, because

• [68], most efforts still focus on the development of unsaturated ester/amide surrogates [69][70][71], which involve α,β-unsaturated imides, N-acyl heterocycles, α-oxophosphonates, α-ketoesters, 3-methyl-4-nitro-5-alkenylisoxazoles and α’-hydroxyenones. These latter substrates have proven to be very

• very narrow range of nucleophiles have been reported to be efficient in this regard (α,α-disubstituted aldehydes [114] and β-ketoesters [115] among others). With the aim of expanding the nucleophile scope of this transformation, in 2014 Hartwig et al. reported a highly diastereoselective iridium

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• in the catalytic cycle of this transformation. From the 1990s, the enantioselective carbenoid insertion into C(sp3)–H bonds starts to be better discussed in the literature. Ikegami and coworkers reported the enantioselective insertion of α-diazo-β-ketoesters into C(sp3)–H bonds catalyzed by rhodium

• porphyrin-based catalyst for enantioselective carbenoid insertion into C(sp3)–H bond. Rhodium porphyrin-based catalyst for enantioselective carbenoid insertion into benzylic C(sp3)–H bond. Enantioselective insertion of α-diazo-β-ketoesters into C(sp3)–H bonds catalyzed by chiral rhodium(II) complexes 17a

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• -type acceptor, by weak hydrogen-bonding interaction between the oxygen atom of the hydroxy group and the indolic proton (Figure 5). Recently, the conjugated addition of indole derivatives to β,γ-unsaturated α-ketoesters was explored [40]. To this end, the catalytic activity of several chiral thioureas

• -ketoesters 26a–f reacted with the substituted indoles 2 in the presence of ent-4 to achieve the corresponding adducts 27 with good yields and enantioselectivities (up to 88% yield, up to 76% ee) (Scheme 11). Although the absolute configuration was unknown at that point, the authors envisioned a plausible

• , establishing a hydrogen bond with the indolic proton. This would conduct its attack over the Re face of the β,γ-unsaturated α-ketoesters, producing the addition in a stereocontrolled fashion. Some additional experimental proofs provided in the article supported this hypothesis [40]. Michael addition to α,β

(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

• same nucleophile 81, Wang and his group combined it with β,γ-unsaturated α-ketoesters 87, as the electrophile, catalyzed by bifunctional indane-derived thiourea 88, to produce derivatives of 3,4-dihydro-2H-pyran 89 (Scheme 30) [49]. This reaction sequence involved a Michael reaction, followed by a

• tandem Michael addition of γ,δ-unsaturated-β-ketoesters 114 to trans-β-nitrostyrene 115 which produced tetrasubstituted cyclohexenols 116 and 117 utilizing Takemoto’s catalyst 77 (Scheme 37) [56]. In a paper that described in more detail the transformation, the authors showed that the substitution of the

• dihydropyrans 122. They utilized the novel tyrosine-derived tertiary amine-thiourea 123 in quite low catalyst loading to catalyze the reaction between α-cyanoketones 118 and β,γ-unsaturated α-ketoesters 87 (Scheme 39) [59]. Initially a Michael reaction occurs, followed by a hemiacetalization reaction, providing

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• trifluoromethyl ketones were later developed using the chiral catalyst 27 (Scheme 13) [29]. The electron-deficient triazolium-derived NHC 23 mediated efficient and chemoselective cross-benzoin reactions of aldehydes and α-ketoesters to produce acyloin products endowed with a quaternary stereocentre [30

• ]. Remarkably, the competing hydroacylation reaction was not observed under these reaction conditions. A variety of aliphatic and aromatic aldehydes functioned as acyl donors, whereas several α-ketoesters could be employed as the electrophilic coupling partner to afford the desired products in moderate to good

• cross-benzoin reaction of aliphatic aldehydes and α-ketoesters. Notably, the reaction affords enantiomerically enriched tertiary alcohols. Excellent levels of enantioselection were obtained by using an electron-deficient valine-derived triazolium salt precatalyst 28 (Scheme 15) [31]. Moreover

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

• (Scheme 11a) [38]. Subsequent reports by Deng and co-workers include, amongst many varieties of Michael acceptor and donor with various CPN/CPD derivatives [39][40][41], an example where β-ketoesters are used as the nucleophilic component [42]. It is on the basis of this work that Lin and co-workers were

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• amino-alcohols, amino acids and carbonyl compounds [15]. Much attention has been devoted to the development of an efficient catalytic asymmetric version of this reaction from readily accessible nitroalkanes and carbonyl compounds [16], such as aldehydes [17][18][19], α-ketoesters [20], α

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• -ketoesters and diazoesters, a reactivity that could be further extended to various other molecular transformations. We believe that these findings could be applied to the synthesis of other biologically active oxo-heterocycles, and thus this is currently under investigation in our laboratory and will be

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• ][25][26]. In this context, we have recently reported a catalytic and enantioselective Michael/Michael cascade reaction in which α-nitro-δ-ketoesters react with nitroalkenes to provide densely functionalized cyclohexanes in excellent yield and stereoselectivity (Scheme 1) [27]. This reaction made use

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• studied the reactivity of various β,γ-unsaturated α-ketoesters, which remain to date the only report dealing with such substrates in Cu-catalyzed ACA of trialkylaluminium [41]. Using the (R)-Binap-based system L4/CuTC, an excellent 1,4-selectivity was achieved with mono-unsaturated substrates. Dienic

• breakthroughs. Nowadays, a number of ACA procedures with a various electron-deficient polyenic substrates (linear and cyclic dienones, dienoates, conjugated thioesters, nitroolefins and nitroenynes, enynones, unsaturated acyl-N-methylimidazoles and conjugated ketoesters) and nucleophiles (dialkylzinc, Grignard

• cyclohexanone from a polyunsaturated cyclic Michael acceptor. Selective conversion of β,γ-unsaturated α-ketoesters in copper-catalyzed asymmetric conjugate addition. Addition of trialkylaluminium compounds to nitroenynes catalyzed by L9/CuTC. Addition of trialkylaluminium compounds to nitrodienes catalyzed by

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• , rhodium carbenoids derived from α-diazocarbonyl compounds transform 2H-azirines 1 to azirinium ylides 5 (Scheme 1) which undergo facile N–C2 bond cleavage to give 2-azabuta-1,3-dienes 3. Recently we showed that the use of α-diazo-β-ketoesters 2 in these reactions, which are finished by 1,6-cyclization of

• cyclize into oxazine 4a under the reaction conditions. According to our previous computational and experimental results for transformations of 3,4-diphenyl-substituted 2-azabuta-1,3-dienes derived from α-diazo-β-ketoesters, oxazine 4a formed via rapid cyclization of azadiene E-3a [15], whereas 2-azabuta

• -ketoesters; b) a high reactivity of azirenooxazole 10j toward acetyl(methyl)ketene (12); c) two competing modes of the attack of 10j on ketene 12, leading to adducts 6j,7j via two short-lived betaine intermediates 13j,13′j and 14j,14′j. It is worthy to notice that the distribution of products 6,7 strongly

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• was used as the OH-reagent along with 1,3-ketoesters. However, the reaction with 1,3-cyclohexanedione gave products in low yields (19–26%). The coupling of a number of substituted salicylaldehydes with formamides was performed; the aldehyde group, which is prone to oxidation, remaining intact [157

• was used [181]. The reaction time is 18 h at 90 °C, the yields of α-ketoesters vary from 42 to 88%. The unusual C–O cross-coupling of primary alcohols 184 with secondary alcohols 185 in the absence of oxidants was performed in the presence of ruthenium complex 186 as the catalyst; the reaction

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

• reactants, even though these are present in the solution in excess to all other species, a fact that is due to the poor ESI response of ketoesters and even more so of aldehydes. In the case of the proline-catalyzed solution (Figure 4a), the catalyst is not visible either, because of an instrumental

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• in 28–64% ee [5]. In a similar fashion, Denmark’s oxazaphosphorinane cis-44a yielded keto esters 46a–c in high optical purities via conjugate addition to enones 41 followed by ozonolysis and oxidative esterification. Using diastereomer trans-44b on the other hand provided ketoesters 46a–c with only

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• olanzapine [105]. The preparation of unsymmetrical 1,4-DHPs by the Hantzsch reaction involving two different β-ketoesters has been reported [106]. The literature survey revealed that the Hantzsch reaction served as a tool for the preparation of C-nucleosides with the C-4-substituted 1,4-DHP moiety as a