An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• choice even the reaction time was prolonged to 2 h (36% yield, Table 2, entry 3). Switching the base Et3N to DBU resulted in a significant decrease of product yield (Table 2, entry 4). Given that the crude azomethine ylide 9a was used without any purification, and 9a might be sensitive to other

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• -hydroxybenzotriazole hydrate (HOBt), N,N’-diisopropylcarbodiimide (DIC), triisopropylsilane (TIS), piperidine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), trifluoroacetic acid (TFA), diisopropylethylamine (DIPEA), acetic anhydride (Ac2O), methanol (MeOH), n-butyric anhydride and solvent for HPLC (acetonitrile (ACN

• )-OH, Fmoc-His(Trt)-OH and Fmoc-Ser(t-Bu)-OH. Pyroglutamic acid (Glp or DBU in DMF (4 times; 2 + 2 + 5 + 10 min

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• Mannich bases with malononitrile catalysed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) [67]. It is known that the use of quaternary ammonium salts offers the easier removal of the amino residue and, therefore, trapping the transient electrophilic species at lower temperature. Carrying out the reactions in

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

• , which in the presence of base (triethylamine or DBU) and trimethylchlorosilane transform into indolo[3,2-b]quinoline derivatives in moderate to good yields. Keywords: carbanions; cyclization; heterocycles; nitroarenes; nucleophilic substitution; silylation; Introduction The indolo[3,2-b]quinoline

• first one, both reagents, C–H acid and nitroarene, upon treatment with a relatively weak base such as DBU and a silylating agent or Lewis acid, undergo slow transformation to the quinoline derivative. In this process, a low concentration of the σH-adduct is postulated. Another approach uses a strong

• used sulfone 1a. We found that no reaction occurred when the sulfone and 4-chloronitrobenzene were treated with DBU and trimethylchlorosilane. Even when we kept these reagents for a prolonged time (up to six days) no product was observed and the starting materials were recovered. When we treated these

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• (Scheme 9). It was found that DBU can promote the decomposition of difluorocarbene to give fluoride which then reacts with difluorocarbene to a trifluoromethyl anion. Both electron-rich and electron-deficient substrates were converted to the corresponding analogues in moderate to good yields, without

• producing byproducts from a pentafluoroethylation. The proposed reaction mechanism is depicted in Scheme 9. First, a phosphonium ylide is formed after treating DFPB with DBU, and then dissociated to generate a difluorocarbene. The difluorocarbene reacts with DBU affording nitrogen ylide I, followed by a

• aromatic iodide. Additionally, the intermediate III is also unstable and decomposes to intermediate IV in the presence of water. And DBU is regenerated after the elimination of HF and decarbonylation. Then, the group of Zhang [22] from GlaxoSmithKline designed trimethylsilyl chlorodifluoroacetate (TCDA) as

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• with various substituted 2-aminophenols in the presence of the strong base DBU which resulted in compounds 22a–e. A subsequent protection group removal yielded compounds 23a–e and made the scaffold ready for cyclization. Initially, CsF was used in place of KF, however, the hygroscopic nature of CsF

• -iodoaniline 32 in 68% yield after isolation [52]. The cyclization was performed via nucleophilic aromatic substitution with DBU and DABCO. Presumably DABCO activates the chlorine and modifies it into a better leaving group allowing the sterically hindered base DBU to abstract a proton from the protected

• a more straightforward and versatile synthetic route. The Stille coupling was changed to a Suzuki–Miyaura coupling and the cyclization was performed directly starting from the free aniline nitrogen, as we found that Boc protection was required only for cyclization when using DBU and DABCO. To faster

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• DBU to provide a free amino group, the 2’-NH2 and 3-OH groups could be differentiated in the next acylation step by using DCC as activating agent for the N-acylation, and Steglich reaction conditions (DCC and DMAP) for the O-acylation. Following removal of the Alloc protecting group was readily

• separation of the anomeric α/β mixture furnished the anomerically pure trisaccharide 15. Next, three acyl residues were introduced at positions 2’, 3’ and 3 by successive deprotection–acylation sequence. The N-Fmoc protecting group was removed using DBU and the resulting free amino group was acylated with (R

• azide 12 with the imidate donor 43 furnished fully orthogonally protected βGlcN(1→6)GlcN 44. Next, the 2’-N-Fmoc group in 44 was removed by treatment with DBU and the first unusual branched acyloxyacyl residue was installed. For the preparation of (R)-3-hydroxy-13-methyltetradecanoic and (R)-3

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• (rt, 24 h) and TBDMS protecting groups were removed with HCl (pH 2, rt, 12 h). (B) Large-scale production of RNAs with cap0 or cap1 by a combination of solid-phase synthesis and enzymatic methylation [111]. Deprotection conditions: DBU (1,8-diazadicyclo[5,4,0]undec-7-ene) in acetonitrile (rt, 3 min

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

• trifluoromethanesulfonyl chloride in the presence of a base, like Et3N or DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in dichloromethane (Scheme 39). The chlorinated products were recovered in excellent yields. Interestingly, when the reactions were conducted in methanol, the selectivity proved to be quite high, as the rate

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• yields by deacylation of 2-(N-acylamino)vinylphosphonium salts with methanol in the presence of DBU (Scheme 19) [34][35]. Spectroscopic properties (IR, 1H and 13C NMR) and X-ray data of the obtained 2-aminovinylphosphonium salts corresponded to the enamine tautomeric form with the domination of β-iminium

• possible only in the presence of a strong base, such as, for example, DBU [34][35][36]. In the case of a real tautomeric equilibrium between aminovinylphosphonium and α-iminoalkylphosphonium cations, the isotopic exchange should occur easily (Scheme 20). Borodkin et al. have recently reported a new method

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• choice of base, leading to the construction of a [7]annulene system (Scheme 5). The use of lithium bases, such as lithium diisopropylamide and lithium hexamethyldisilazide, induced HF eliminations as well as substantial HI elimination. However, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) exclusively

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• isolated yield (Table 1, entry 3). Methanol proved to be an unsuitable solvent for this reaction in terms of both conversion and selectivity (Table 1, entry 4). Likewise, diisopropylethylamine (DIEA) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were found to be not superior to TEA as catalysts (Table 1

• the Michael-type adduct, phenyl 2-(3-methyl-2-oxo-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-4-yl)acetate (6a). The presence of DBU caused substantial decarboxylation of starting reagent 1a (Table 3, entry 3). This unwanted process necessitated using of up to 6 equivalents of 1a to reach a

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• substrate 9 to be processed with TMG or DBU (2.5 equiv) and ethyl cyanoacetate (10, 1.1 equiv) at 50 °C in quantitative conversion. Based upon these screening results we devised a simple flow set-up where two stock solutions were united at a simple T-mixing piece and subsequently directed into a heated flow

• –96%. Process 2 (EtOAc): Three EtOAc stock solutions were prepared. Solution A: DBU (3.75 M, 2.5 equiv), solution B: ethyl cyanoacetate (1.65 M, 1.1 equiv), and solution C: 4-chloro-3-nitrobenzotrifluoride (1.5 M, 1.0 equiv). Stock solutions A (0.6 mL/min) and B (1.2 mL/min) were pumped from their

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• various solvents (e.g., PhMe, THF, and CH2Cl2) at different temperatures. Hereby Deoxofluor in CH2Cl2 with or without adding DBU was found to be the most suitable reagent. The diol derivatives, obviously, are expected to deliver the corresponding difluorinated products. In spite of this anticipation, the

• the presence of 4 equiv DBU as the base [28] the reaction time could be decreased to 10 min with a slightly increased yield of the product (Scheme 1). This observation led us to conclude that out of the two hydroxy groups only that attached to C-3 takes part in the reaction and is substituted via the

• amide O-atom. Increasing the amount of Deoxofluor to 4 equiv resulted in the exclusive formation of the fluorine-containing oxazoline derivative (±)-3. Note that the addition of DBU did not have a significant effect on this reaction. When isolated hydroxyoxazoline (±)-2 is subjected to the fluorination

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• phthalocyanine can be synthesized by using phthalonitrile in which one trifluoroethoxy group was introduced at the α- or β-position (Scheme 9). The target DDPc was successfully obtained in moderate yield by heating trifluoroethoxy-substituted phthalonitrile in the presence of DBU and a lanthanoid acetylacetone

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

• their reactions with enolates. Thus, our group has demonstrated that nitrosoacetals of nitrosoalkenes (N,N-bis(silyloxy)enamines 3) smoothly react with 1,3-dicarbonyl compounds in the presence of TBAF or DBU to give the corresponding oximes 6 in moderate to good yields (Scheme 3) [24]. The process is

• (silyloxy)enamines 3 under these conditions. Nitronate anions also react as C-nucleophiles with N,N-bis(silyloxy)enamines 3 producing β-nitrooximes 7 in good yields (Scheme 4) [20][25]. Efficient coupling of DBU-nitronate salts derived from primary nitro compounds with enamines 3 was achieved at –78 °C upon

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• yield of the cyclic ether was still low (Table 2, entry 6). Microwave heating was not helpful (Table 2, entry 7). The non-nucleophilic base DBU was not effective in promoting the cyclization, either (Table 2, entry 8). We observed small amounts of products arising from the dehydration of 15 in the 1H

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• propargylic derivatives 4 [28] with aromatic aldehydes. Then, the DBU-mediated isomerization afforded the desired enones 6a–e in 21–66% yields (Scheme 2 and Table 1). For the synthesis of the desired nitrogen heterocycles, we started our study by reacting 6a with 2-aminopyridine in the presence of AlCl3 and

• DBU (1,8-diazabicycloundec-7-ene) under the same conditions as mentioned above, the desired imidazopyridine derivative 7a was isolated in 33% yield (Scheme 4). This one-pot process gives an overall yield very close to the two-step reaction (38%). Further, the halogen-substituted substrate 7e appeared

• (4 mL), then DBU (0.42 mL, 2.82 mmol, 1.5 equiv) was added and the reaction mixture was stirred at room temperature. After 2 h, 19F NMR showed 100% conversion and the reaction mixture was neutralized with a saturated solution of NH4Cl. After extraction with ethyl acetate, the organic phases were

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• , but also provides the useful heterocycles which are not easily achieved through other protocols. Results and Discussion In the initial studies, we treated methyl 4-(3-(2-(allylthio)phenyl)-3-methoxyprop-1-yn-1-yl)benzoate (1a) with DBU (0.1 equiv) in THF at 50 °C under N2 for 12 h (Table 1, entry 1

• temperature was found to be less effective for the reaction (Table 1, entry 13). Without the base, no reaction occurred, implying that the reaction proceeded exclusively through the allenic intermediate (Table 1, entry 14). Thus, the optimal reaction conditions were DBU (0.2 equiv) under nitrogen in THF at 50

• reaction proceeded under mild conditions to produce useful benzothiophene and indole derivatives. Examples of biologically active benzothiophene derivatives. Synthesis of benzothiophenes. Reaction conditions: 1 (0.5 mmol), DBU (0.1 mmol), THF (2.0 mL), 50 °C, 12 h, under N2. Yields are isolated yields

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

• [32][33][34][35][36]. Gao and co-workers described the I2-catalyzed cyclization of β-acylaminoketones using tert-butyl hydroperoxide as the oxidant; notably, adding DBU led to oxazole formation whereas adding K2CO3 generated oxazolines [37][38]. Our proposed new approaches to oxazoline formation

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• our previous researches [4][51], it is found that the bases used have a significant influence on the yields of the reaction. Thus, several bases such as NaOH, KOH, Cs2CO3, K2CO3, t-BuOK, Et3N and DBU were investigated and the results are shown in Table 1. It is notable that both inorganic and organic

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• reported intriguing 1,3-proton shift of 4,4,4-trifluorobut-2-yn-1-ols was successfully extended to the 4,4,4-trifluorobut-2-en-1-ol system under metal-free conditions to afford the corresponding saturated ketones in high to excellent chemical yields using such a convenient and easy-to-handle base as DBU at

• excess amount of CsF, the resultant product (E)-2Fb was further converted in situ to the corresponding saturated ketone (E)-5b (R = Ph). Confirmation of this process was performed by the action of DBU, resulting in 95% conversion of the starting allylic alcohol (E)-2Fb [14]. Quite recently [15], the same

• -less expensive DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), whose results are reported in this article in detail. Results and Discussion Preparation of substrates (E)-6 was carried out by way of our recently reported one-pot procedure [16]: thus, after reaction of an appropriate Grignard reagent and ethyl

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• the sultam before the second equivalent undergoes the desired nucleophilic addition to the carbonyl group. All attempts to re-oxidise the sultam 15 to the sulfonimide 13, using Cl2/pyridine [37] or N-tert-butylphenylsulfinimidoyl chloride/DBU [38] under literature conditions, were unsuccessful due to

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

• coupling, acetate protection of the newly generated hydroxy group and DBU-mediated elimination. This three-step sequence proceeded as shown in Scheme 6 with excellent yields (94%) giving the triene 33 as a single diastereomer, which demonstrates the usefulness of aldol condensations in complex target