Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• selective formation of the β(1→4) linkage in the [2 + 2] coupling. Cleavage of the anomeric 4-methoxyphenyl group followed by treatment with trichloroacetonitrile and DBU gave glycosyl donor 1 in high yield. For the synthesis of acceptor 2, diol 6 was selectively acylated at position 6 using 1.1 equiv of

• DBU. The glycosylation reaction with 2-propanol using TMSOTf as Lewis acid at 0 ºC cleanly provided the β-isopropyl glycoside 13 in 65% yield. Interestingly, no α-anomer was detected in the reaction mixture. Finally, cleavage of the levulinyl group using hydrazine monohydrate in pyridine/acetic acid

• = pivaloyl; PMP = 4-methoxyphenyl. Reagents and conditions: a) TMSOTf, CH2Cl2, 0 °C, 30 min, 97%; b) (HF)n·Py, THF, 0 °C, 20 h, 90%; c) Ac2O, Py, 24 h, 97%; d) CAN, CH2Cl2/CH3CN/H2O, 0 °C, 1 h, 99%; e) Cl3CCN, DBU, CH2Cl2, 9 h, 98%. CAN = ceric(IV) ammonium nitrate. Reagents and conditions: a

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• , a literature search pointed out the use of an excess of DBU and heat [38][39]. However, boiling compound 40 in toluene in the presence of an excess of DBU led, after chromatography, to only 24% of the benzyl ester 41. Since, amongst few side reactions, we suspected a benzylester cleavage, we

• undertook this reaction under argon in ethanol at 110 °C using a microwave reactor along with only one equivalent of DBU and these changes provided us with the ethyl ester 42 in a 51% yield. Finally, a far more simple procedure was found by just adding a catalytic amount of hydrogen chloride in 1,4-dioxane

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• Soumitra Guin Raman Gupta Debashis Majee Sampak Samanta Discipline of Chemistry, Indian Institute of Technology Indore, Simrol, Indore, 453552, Madhya Pradesh, India 10.3762/bjoc.14.254 Abstract An intriguing DABCO-catalyzed and DBU-promoted one-pot synthesis of an important class of (2

• cyclic sulfamidate imines and MBH acetates of acrylate as coupling partners [68]. Herein, we further present a DABCO-catalyzed and DBU-promoted sequential one-pot procedure for the access to the interesting class of (2-hydroxyaryl)nicotinates/nicotinonitriles from N-sulfonyl ketimines and MBH adducts as

• ) were obtained when the reaction was conducted at 60 °C (entry 2, Table 1). By increasing the temperature as well as the loading of DABCO (1.0 equiv, entry 3, Table 1), a similar result was observed. At this situation, we surmised that step II may require a stronger base like DBU which will facilitate

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• presence of bases (e.g., DBU) [12], Pd-catalyzed cycloalkenylation of a silyl enol ether [13], or base-promoted ynone carbocyclizations [14][15]. Another approach through an aldol cyclization, forming the C1–C7a bond instead, has also been reported [16]. Different strategies were developed by Overman

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• higher hydrazine concentration (4% in DMF) and longer treatment (12 × 5 min) for the complete removal of the protecting group. However, ivDde is more stable in circumstances (2% DBU, 2% piperidine in DMF) used for the Fmoc removal. To avoid the unwanted Dde removal during the synthesis ivDde was applied

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• ether bond at the C17 position under acidic conditions. Synthesis of spinetoram J analogues All carbohydrates and alcohols were activated by CNCCl3 with DBU as catalyst initially to afford glycoside donors, and then the 17-pseudoaglycone of spinetoram J was glycosylated with donors in the presence of

• -methylrhamnose (0.91 g, 4.09 mmol) was dissolved in 20 mL CH2Cl2, then CNCCl3 (0.81 g, 5.61 mmol) and 0.15 mL DBU was added. The mixture was stirred at room temperature for 20 min, then diluted with CH2Cl2 and washed with saturated sodium bicarbonate solution (3 × 10 mL). The combined organic layers were dried

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• ambient temperature and pressure [19][20][21][22]. Furthermore, cyclic amidines and guanidines, such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), exhibited an excellent efficiency of CO2 capture and release [23][24][25][26][27][28][29][30][31][32][33]. In

• structure of the guanidine moiety [39]. Furthermore, we also have demonstrated that the adsorption performance of CO2 was fairly different under dry and wet conditions [35]. Previously, Jessop et al. described that the bicarbonate salt of DBU and CO2 was obtained in the presence of water and never confirmed

• in the absence of water [23]. Moreover, Pérez et al. indicated that the DBU–CO2 complex was assigned as the zwitterion adduct of DBU and CO2 involving water by 13C NMR, TGA, and elemental analysis, although the bicarbonate salt was formed due to hydrolysis in the DBU–CO2 carbamic complex involving

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• alkylated and removed from the equilibrium between macrocycle 6 and 7. Macrocyclization under the optimal conditions (Table 1), followed by in situ post-functionalization (DBU 2.2 equiv, ethyl bromoacetate 3 equiv) in a one-pot procedure also led to a shift towards the functionalized [3 + 3] adduct 19

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• -ene (DBU) to [2]rotaxane R1 in CDCl3 to deprotonate the ammonium moiety, the DB24C8 macrocycle moved to the amide station. As shown in Figure 2, the protons H12, H13 shifted upfield (ΔδH12 = −0.99 ppm and ΔδH13 = −0.75 ppm) and incorporated into one signal peak from two while the H11 and H10 shifted

• ), H11 (peak C) (around the DBA recognition site) and methylene protons on the functional crown ether indicate that the DB24C8 macrocycle was located on the DBA site, corresponding to the structure of [2]rotaxane R1. After addition of 2 equiv DBU to the solution of R1, the NOE correlations between the

• . Partial 1H NMR spectra (400 MHz, CDCl3, 298 K). (a) [2]Rotaxane R1, (b) deprotonation by the addition of 2.0 equiv of DBU to (a), (c) reprotonation with addition of 3.0 equiv of TFA to (b). Partial 2D ROESY NMR spectra (500 MHz, CDCl3, 298 K). (a) [2]Rotaxane R1, (b) deprotonation with addition of 2.0

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• published a direct one-pot synthesis of exclusively β-configured nucleosides from unprotected or 5-O-monoprotected D-ribose using optimized Mitsunobu conditions with various purine- and pyrimidine-based heterocycles. Here, DBU was applied first, followed by DIAD and P(n-Bu)3 [106]. Two years later Seio and

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• ), 80% (11); b) TCCA, CH3COCH3/H2O (4:1), rt, 85% (12a), 89% (12b); c) CCl3CN, DBU, DCM, 0 °C, 93% (6b), 90% (6c). Preparation of L-rhamnosyl acceptor 5. Reaction conditions: a) Py, BzCl, rt, 12 h, 99%; b) DDQ, DCM/H2O (19:1), rt, 2 h, 83%. Preparation of ribitol acceptor 7. Reaction conditions: a) Me2C

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• nature of anisoles induced by the electron-donating methoxy group. Taking into account the above-mentioned observations [18][34][35][36][37][38], couplings were performed in the presence of DBU, NaOt-Bu, KOt-Bu or Cs2CO3 as the base. Toluene was chosen as a solvent, and the reactions were carried out

• and 9) as bases seemed to be more advantageous over the use of DBU (Table 1, entries 1 and 7). Concerning the ligand applied, it can be stated that reactions with X-Phos (Table 1, entries 1–6) resulted in higher yields in comparison to couplings with BINAP (Table 1, entries 7–9). As seen in Table 1

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• GmbH, Marktredwitz, Germany) were used for the synthesis except Fmoc-Lys(Mtt)-OH that was applied for the development of branching in the peptide. The protocol of the SPPS was similarly as described in [17] as follows: (i) DMF washing (4 × 0.5 min), (ii) Fmoc deprotection with 2% DBU, 2% piperidine

• (Biolegend, San Diego CA). Samples were detected and analyzed by using an Attitude® Acoustic Focusing Cytometer (ThermoFischer Scientific). Schematic synthesis of cyclic KNGRE (A) and XNGRE (B) drug conjugates. a) Mtt-cleavage: 2% TFA/DCM; b) Fmoc-Aaa(X)-OH coupling; c) Fmoc-cleavage 2% piperidine/2% DBU/DMF

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• the base and performed the reaction in DMSO at 115 °C for 12 h [13]. Good to high yields of terminal alkynes were obtained (50–98%). Also DBU (4 equiv) in MeCN at room temperature is effective to carry out the second step of the Corey–Fuchs reaction, affording good to high yields of arylalkynes. In

• the latter reaction DBU acts both as base and as organocatalyst [14]. In all cases, an excess of a strong base or high temperature are necessary for the reaction to proceed. An overview on the importance of the Corey–Fuchs reaction for the synthesis of natural products has been pointed out by Heravi

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