Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• solubility of Cs2CO3 in toluene and 1,4-dioxane [24]. Using K2CO3 in MeCN, Longworth et al. have obtained 10 with a similar degree of N-1 regioselectivity (ratio N-1:N-2 = 2.8:1) [26]. However, altering solvent polarity when employing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a base (Table 1, entries 15–17

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -containing 1,2,3-triazole derivatives 30 from the reaction of glycosyl azides 28 with enolates of active ketones and esters 29 in the presence of DBU in DMF at 70 °C (Scheme 12) [43]. Diverse monosaccharide and disaccharide azides were successfully reacted with a variety of enolates of active ketones and

• the use of a catalytic amount of DBU in DMSO at room temperature [46]. The cyclic enones 43 were reacted with the α-azidostyrenes 44 containing groups such as Cl, F, and OMe to form the corresponding products (Scheme 16). The o-, m-, and p-tolylvinyl azides facilitated a good to excellent yield of the

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• inorganic bases, such as Et3N, K2CO3, and DBU. Along with the “traditional” reaction performed in solution, a mechanochemical approach using ball milling was also tested. The obtained results are collected and compared in Table 1. They show that the best results were achieved using dry THF as a solvent and

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• were formed that were still insufficient for complete characterization. Intending to improve the yield of 3aa, we screened various solvents, non-nucleophilic organic bases such as triethylamine and DBU, and several inorganic bases like K2CO3, Cs2CO3, and NaH (Table 1, entries 2–6). After systematic

• inert atmosphere prior to use. Organic bases, including DIPEA, Et3N, and DBU, were stored over anhydrous KOH pellets. In vitro cytotoxicity studies Cytotoxicity analysis in cancer and macrophage cells Cancer (MCF7, A431, A549, HEK293 or HeLa cell lines) or RAW264.7 cells were seeded in a 96-well plate

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• industrialized total synthesis of a nontrivial natural product. The original experimental protocol was recently improved by replacing the inorganic base (KOH, NaOH) with the amidine base diazobicycloundecane (DBU) as well as ethanol with n-propanol [49]. The type-III Guareschi reaction is a three-component

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• -Michael reaction, it was possible to reach either cis- or trans-isoindolines, 69 and 70, respectively, from the same precursor 68. The authors proposed that the thermodynamically more stable cis-isomer 69 is formed when TBAF was used. Meanwhile, working under kinetic conditions (DBU as base), trans-isomer

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• , Fu and colleagues [35] received the target product 40 with 23 W CFL irradiation of a solution containing 1-(4′-hydroxy-[1,1′-biphenyl]-2-yl)ethanone O-(2,4-dinitrophenyl)oxime (39) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in CH3CN (Scheme 13). Ready-made DBU serves two roles: base and electron

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• CBr4 or I2, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or NaH as the base, and a malonate-derived substrate. The adduct is synthesized in a slightly higher yield by direct treatment of fullerene with malonates. As noted above, a decrease in the strain of the fullerene core is the driving force of its

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• regioselectivity of SNAr reactions was proved by 13C NMR comparison of the products 3a–i with similar compounds from literature [61]. Intriguingly, we were able to conserve the acetate protecting groups in product 3j, when the SNAr reaction was performed in the presence of DBU used as base. The artificial

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• as a Michael acceptor. Stronger bases, such as NaH and t-BuOK seemed to be preferable (Table 2, entries 3 and 6), and amines such as DBU and 1,1,3,3-tetramethylguanidine (TMG) were found to be insufficient (Table 2, entries 10 and 11). Judging from the possible mechanism, this process was considered

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• [80], compound (Z)-(+)-143a delivered the bromodiene (Z,Z)-(+)-145a in good yield and stereoselectivity. Isomerization of (Z)-(+)-143a to (E)-(+)-143b was carried out successfully using sterically hindered base DBU or DABCO. Treatment of (E)-(+)-143b with 144 using the boron-Wittig reaction [79

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• , 70%, 97.3% ee; iii) 1. DMAP, Et3N, MsCl, CH2Cl2; 2. DBU, CH2Cl2, 70% over two steps; iv) CH2=CHCH2MgCl, THF; v) HCl (4.0 M in dioxane), CH2Cl2, 78% over two steps; vi) PdCl2, CuCl, DMF/H2O (20:1), 23 °C, 93%; vii) KOSiMe3, 23 °C, 35 min; viii) NOPF6, DME, 80% over two steps; ix) 2-butanone ethylene

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tetracyclic compound 56. Dihydroxylation of freshly prepared 56 with OsO4 and then selective tosylation afforded 57 in 39% yield over two steps. Exposure of 57 to DBU upon heating gave the elimination product 58, which was subjected to an oxidative rearrangement with PDC to give enone 59 in 68% yield. Copper

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

•  3). Thioamides 1f,g,t were converted to 5-arylamino-1,2,3-triazoles 1i–k by heating at reflux in n-propanol in the presence of DBU and these rearranged thioamides were then treated with sulfonyl azide 2c,f and kept at the same temperature for 17‒31 h. After flash column chromatography, pure N

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• the complex [Zn(49)]2+. The liberated zinc(II) ions replaced the Li+ ions in the nanoswitch [Li(35)]+ and translocated them onto the luminophore 36, thus finally generating the state SelfSORT-II composed of 49•H+, [Zn(35)]2+, and [Li(36)]+. In the return process, the deprotonation of 49•H+ by DBU

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• (bridgehead alkenes are only stable in large ring systems), elimination was attempted only with (rac)-2a,b, (rac)-5a, (rac)-6b, (rac)-8a,b, and (rac)-11a,b. DBU in THF under reflux was insufficient to promote the elimination of the halofluorinated diesters (rac)-2a,b, (rac)-5a, and (rac)-6b. In contrast, the

• that of the corresponding stereoisomers, it is more likely that the epimerization occurs after the formation of (rac)-T10. Concerning (rac)-8a and 8b as well as (rac)-11a and 11b, the reagent preference was exactly the opposite: DBU in THF under reflux was effective, while t-BuOK in THF under reflux

• interactions are marked with blue two-headed arrows. Mechanism of the reaction of the cyclopropanation of the compounds (rac)-2a,b and (rac)-5a with t-BuOK. Presumed mechanism of the reaction of the compound (rac)-6b with t-BuOK. Cyclizations of halofluorinated tetrahydrophthalimides with DBU. Relevant NOESY

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• products were formed when stronger bases such as triethylamine or DBU were used (Table 1, entries 2 and 3). Later on, inorganic bases in combination with a phase transfer agent such as benzyltriethylammonium chloride (TEBAC) were tried as catalysts for the same reaction. Similarly, no products were

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• -phenyltrifluoroacetimidate glycosyl donor 20 by reaction with 2,2,2-trifluoro-N-phenylacetimidoyl chloride in the presence of base DBU [14]. The monoacylated derivative 15 is also the key building block for the synthesis of lipid X monosaccharide 1 (Scheme 3). After the N-Troc protecting group was removed as described above

• , DMAP, CH2Cl2, rt, 85%; (h) Zn/AcOH, CH2Cl2, rt; (i) DIPEA, FmocCl, CH2Cl2, rt, 80% (2 steps); (j) PhBCl2, Et3SiH, CH2Cl2, MS 4 Å, −78 °C, 80%; (k) HF/pyridine, THF,−40 °C to rt, 93%; (l) DBU, ClCN(Ph)CF3, CH2Cl2, 95%. Synthesis of lipid X monosaccharide 1. Conditions: (a) Zn, AcOH, CH2Cl2, rt; (b) acid

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• observed (Table 1, entry 2). At this stage, we realized that DMSO was a better choice for this transformation as the reaction required a shorter time and afforded the product 2bA in a better yield. Then, other amines such as NMP, Et3N, DBU, and DABCO were also investigated. The use of NMP as an activator

• combination of DABCO and DMSO also afforded the desired product via a clean reaction within 20 min, although only 60% yield of the product was obtained (Table 1, entry 10). This promising result using DABCO encouraged us to explore other amines like DBU, ʟ-proline, pyridine, DMAP, and pyrrolidine as an

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• acidic conditions, rapid aqueous work-up was conducted, followed by reduction with NaBH4, yielding the corresponding primary alcohol 8 in 81% yield over two steps. The transformation to azide 9 was accomplished by deprotonation using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and reaction with

• °C to 25 °C, 1.5 h; c) NaBH4, THF/MeOH 1:1 v/v, 0 °C, 1 h, 81% (2 steps); d) DPPA, DBU, PhMe, 25 °C, 18 h, 98%; e) 1) MeOTf, CH2Cl2, 25 °C, 2.5 h; 2) NaBH4, THF/MeOH 4:1 v/v, 0 °C, 2.5 h; 3) oxalic acid, THF/H2O 4:1 v/v, 25 °C, 20 h, 78%. Overall yield from 4-bromobenzaldehyde to 3: 56% (5 steps

• h, 91%; h) 1) DPPA, DBU, PhMe, 25 °C, 15 h; 2) NaN3, PhMe, 60 °C, 4 h, 87%; i) 1) MeOTf, CH2Cl2, 25 °C, 2.5 h; 2) NaBH4, THF/MeOH 4:1 v/v, 0 °C, 2.5 h; 3) oxalic acid, THF/H2O 4:1 v/v, 25 °C, 20 h, 86%. Overall yield to 5: 45% (8 steps). The molecular structure of 5 shows 50% probability ellipsoids

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• afforded the corresponding products 59 in good to excellent yields (Scheme 36). The authors then studied the elimination of the trifluoromethyl group from this library of PK adducts, building upon their own experience in the field (vide supra, Scheme 34). Thus, by subjecting enones 59 to treatment with DBU

• aforementioned DBU-mediated detrifluoromethylation (Scheme 37) was achieved for substrates 68 in most cases with low to moderate yields, while the corresponding products could not be isolated starting from substrates 69. In 2012, Konno and co-workers reported the synthesis of 2-fluoralkyl-2-cyclopentenones

• Diels-Alder reactions [70]. Tentative mechanism for the nucleophilic addition/retro-aldol reaction sequence. Catalytic PKR with norbornadiene [70]. Scope of the PKR of trifluoromethylalkynes with norbornadiene [72]. DBU-mediated detrifluoromethylation [72]. A simple route to enone 67, a common

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• into two different dimesylated nucleosides. After the deprotection with Hg(OAc)2 in the presence of TFA, the dimesylated thiols 127 and 130 generated companied with the thietane-fused nucleoside 128 in one case. Further the treatment of the dimesylated thiols 127 and 130 with DBU gave rise to the