Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• from low reactivity. The solvent-free mechanochemical polymerization of trimethylene carbonate using the organocatalysts 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) are examined herein. The polymerizations under ball-milling conditions exhibited significant

• biomedical applications [24]. The amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is one of the best studied and most popular organocatalysts for ring-opening polymerizations of cyclic carbonates and lactones [25][26][27]. In contrast to the high activity of lactone polymerization, cyclic carbonate

• polymerization usually requires long reaction times to achieve high conversions (Table 1) [27]. The DBU-catalyzed polymerization of trimethylene carbonate in chloroform, tetrahydrofuran, toluene, and methylene chloride converted less than 5% monomer into poly(trimethylene carbonate) (PTMC) within 1 h (Table 1

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• yield of pure product was increased to 65% in ethanol. The yield of the reaction in the presence of DBU and diisopropylethylamine (DIPEA) as a base were 61 and 60%, respectively. This means that the type of base does not play an effective role in this reaction. The effect of different solvents (EtOH

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• were unable to access 2 (Scheme 7). Instead, the major product isolated in both cases was novel heterocycle 35. It is likely that cleavage of one of the pivaloxymethyl groups, followed by intramolecular cyclisation, results in the formation of 35. Microwave heating of 33 in the presence of DBU also

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• deprotection with TiCl4 the hydroxy-functionalized diazocines 4a and 4b were obtained [32]. The hydroxy groups in 4a and 4b were successfully converted into azides using 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) and DBU [33]. The synthesis was completed with a Staudinger reaction to obtain

• ; iii) Zn, Ba(OH)2 H2O/EtOH, and CuCl2/O2, NaOH/MeOH; iv) Ti(Cl)4, DCM; v) ADMP, DBU, THF; vi) PPh3, H2O, THF; viii) TsCl, DMAP, TEA, DCM, and t-BuOK, THF. Photostationary states (300 K), absorption maxima and half-lives (298.15 K), determined by 1H NMR and UV–vis spectroscopy in acetonitrile

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• satisfying. After Boc removal at 22, HATU/HOAt-mediated coupling with Boc-protected L-alanine afforded dipeptide 26, which was saponified and coupled with TIPS-protected threonine methyl ester (obtained with TIPSCl/DBU/MeCN) to provide tripeptide 27 (Scheme 5). Peptides 26 and 27 were obtained in nearly

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• min, 95%; c) i. DBU, DCM, rt, 1 d; ii. TBAF, THF, 0 °C, 10 min, 87% (over two steps). LDA = lithium diisopropylamide, HMPA = hexamethylphosphoramide, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, TESCl = triethylsilyl chloride. Supporting Information Supporting Information File 206: Experimental part.

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• longer residence time resulted in a lower yield (10.5 min = 37%). Similar observations were previously made for glycosylation reaction under continuous flow conditions [23][24][25][26]. A larger amount of DBU did not increase the yield. For the glycosylation reactions with glycosyl donor 5 a multiple

• step reaction arrangement starting from pyranose 4 was set up. Scheme 4 shows this setup of a suitable cascade reaction in which DBU, trichloroacetonitrile and pyranose 4 were pumped through the first flow reactor (R1) followed by the addition of the alcohol and TMSOTf through the second reactor. Table

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• presence of DBU [34] resulted in the formation of (4,6-O-benzylidene-2,3-di-O-benzyl-β-D-mannopyranosyl)-(1→4)-6-O-benzoyl-2,3-di-O-benzyl-α,β-D-glucopyranosyl trichloroacetimidate (18) in 90% yield (Scheme 2). In the next set of reactions, the disaccharide trichloroacetimidate derivative 18 was allowed to

• temperature, 2 h, 98%. Reagents and conditions: (a) Benzoyl chloride, pyridine, 0 °C, 3 h, 75%; (b) Tf2O, BSP, TTBP, CH2Cl2, MS 4 Å, −60 °C, 1 h then compound 10, −78 °C, 2 h, 65%; (c) PdCl2, CH3OH, 0 °C to room temperature, 3 h, 75%; (d) CCl3CN, DBU, CH2Cl2, −10 °C, 90% (mixture of α and β). Reagents and

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• that the amine could play a role in promoting the [2,3]-sigmatropic rearrangement. After a screening of different tertiary amines, Rubin et al. found that DBU could be used as a base in the phosphinylation reaction but also as an efficient catalyst for the subsequent [2,3]-sigmatropic rearrangement of

• diastereoselectivity. However, the sigmatropic rearrangement of the highly hindered di(tert-butyl)phosphinite 6j and tetra(isopropyl) phosphorodiamidite 6k did not occur (Scheme 7) [37]. The mechanism proposed by Rubin et al. involves a reversible addition of the Lewis base (DBU) on the cyclopropene double bond at C2

• ’ would then be obtained and would eventually produce the diastereomeric phosphine oxides 7 and 7’. Computational studies indicated that the facial selectivity of the initial attack of the Lewis base (DBU) was not responsible for the observed diastereocontrol because of the low difference between the

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• aerobic oxidation of easily available cyclopropanols 91 via intermediate formation of peroxyketone intermediates 145, followed by enantioselective epoxide formation in the presence of a poly-L-leucine catalyst and DBU (Scheme 40) [120]. In 2014, a practical method for the conversion of 1,2-disubstituted

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