Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• -sulfonylamidines selectively [17]. The following screening of organic (Table 1, entries 2‒7 and 8) and inorganic (Table 1, entry 10) bases at room temperature revealed that using DBU resulted in the highest yield of triazole 3a. Analysis of experiments with 100 mol %, 120 mol %, and 80 mol % of DBU (Table 1

• , entries 2‒7) showed that the use of 100 mol % of DBU is optimal for the selective synthesis of triazole 3a in high yield (Table 1, entries 4 and 5). A study of the reaction medium revealed that common organic solvents are highly efficient for this cascade reaction (Table 1, entries 1‒11). Among the

• solvents screened, 1,4-dioxane was found the best solvent in terms of yield of the target product, solubility of the reagents, and ease of separation of the product. Thus, the optimal conditions found were reacting amidine 1 with azide 2 in the presence of DBU in a 1:1:1 ratio in 1,4-dioxane at room

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• . Therefore, while confirming the presence of the adduct, we could not quantify it. The next choice was DBU (1,8-diazabicyclo[5,4,0]undec-7-ene). The DBU-BF3 adduct is reported to be very stable in water and in air and not subjected to hydrolysis [115]. The DBU solubility in BMIm-BF4 was confirmed by NMR

• analysis (amidine carbon atom at 161.6 ppm in BMIm-BF4, taking as internal reference the imidazolium C2 at 136.4 ppm) [116]. The addition of an excess of BF3·Et2O to the solution of DBU in IL shifted the DBU amidine signal to 166.0 ppm, confirming the rapid formation of the adduct (see Supporting

• oxidation of pure BMIm-BF4 (divided cell, galvanostatic conditions) and stopped the electrolysis after 60 C (corresponding to 0.6 mmol of electrons). At the end of the electrolysis, 0.6 mmol of DBU were added to the anolyte and the mixture was kept under stirring at room temperature for 30 min. Then the

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• -cyanoethyl groups were removed by flushing the CPG with a solution of DBU in ACN. Under these conditions, the ODN remains on CPG and the nucleobases remain protected, both of which decrease the probability of the Michael addition side reaction. After washing off acrylonitrile, the CPG was subjected to

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• nitrile of isatin 2a as standard reaction. The main experiments are briefly summarized in Table 1. At first, the reaction in DCM in the presence of common organic bases such as DMAP, DABCO, or DBU gave the expected spiro[indoline-3,5'-[1,2]diazepine] 3a in low to moderate yields (Table 1, entries 1–3

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• synthesis began with the generation of substituted 2-bromo-1-aminonaphthalenes 9 and 10 (Scheme 6). After α-bromination of tetralones 1 and 2, intermediates 3 and 4 underwent elimination/aromatization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford 2-bromo-1-naphthols 5 and 6 in fairly good yield

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• commences with a copper-free alkynylation using DBU as a base at 100 °C. This step is followed by the addition of KOt-Bu and reaction at 100 °C for 15 min and subsequent reaction with N-iodosuccinimide (3) at room temperature. Finally, the reaction with alkyl halides 4 at room temperature gives the title

• , 122 mg, 1.20 mmol), DBU (457 mg, 3.00 mmol), and DMSO (1.50 mL) were added under nitrogen. The reaction mixture was heated at 100 °C (oil bath) for 2 h. After cooling to room temperature, potassium tert-butoxide (505 mg, 4.50 mmol) and DMSO (1.50 mL) were added to the reaction mixture and heated to

• , 25.0 µmol) and (1-Ad)2PBn·HBr (23.6 mg, 50 μmol) were placed in an oven-dried Schlenk tube with magnetic stirring bar under nitrogen. Then, 2,4-dibromoaniline (1c, 254 mg, 1.00 mmol), phenylacetylene (2a, 245 mg, 2.40 mmol), DBU (457 mg, 3.00 mmol), and 1.50 mL DMSO were added and flushed with nitrogen

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• -chain alkyl ethers in the presence of DBU under relatively mild conditions (Scheme 29b) [92]. In 2018, Wang et al. developed the cobalt-catalyzed oxidative CDC reaction of 2-arylimidazo[1,2-a]pyridines with isochroman using molecular oxygen as an oxidant (Scheme 30) [93]. These reactions involved a

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• selectively produced by using differently substituted 3-methyleneoxindoles (reaction 4 in Scheme 1). Herein, we wish to report these interesting results. Results and Discussion At first, 3-isatyl-1,4-dicarbonyl compound 1 was prepared by DBU-catalyzed Michael addition reaction of dimedone and ethyl 2-(2

• % (Table 1, entry 7). When DABCO or DBU was employed as base, the yield of 3a decreased to 36% and 29% yield, respectively (Table 1, entries 8 and 9). When the loading of ammonium acetate was increased to 0.8 mmol and 1.0 mmol, the yield of 3a increased to 85% and 82% (Table 1, entries 10 and 11

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• reduction to PC•− ensures higher concentrations that are directly user-influenced. Upon activation, PC1 could successfully reduce various aryl halides generating borylated products in modest to excellent (30–99%) yields. Control experiments confirmed that light, catalyst and DBU as a sacrificial electron

• a two-photon process. DBU was found to quench the steady-state fluorescence of *PC1 with a quenching rate constant two orders of magnitude smaller than the diffusion rate constant in DMSO at 298 K and one order of magnitude greater under the borylation reaction conditions (i.e., 0.20 M DBU) than the

• intrinsic decay rate of *PC1. Since no quenching by 1d or B2pin2 could be observed, the formation of PC1•− can be attributed exclusively to the thermodynamically favored reductive quenching of *PC1 by DBU. Nanosecond laser flash photolysis techniques were employed to directly monitor the back electron

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• of the photoproducts (Table 2). Based on the structure of compound 11a we assumed that it could be converted into a polyaromatic product using conventional synthetic methods. However, the use of different systems (TsOH/toluene, HCl/EtOH, DBU/EtOH, MeONa/MeOH) resulted only in the decomposition of the

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• , entry 5). Lowering the temperature to 60 °C had a deleterious effect (Table 1, entry 6). Likewise, reducing the stoichiometry of pyridine to 1 equiv proved detrimental (Table 1, entry 7). Replacing pyridine with other organic and inorganic bases such as Et3N, DBU, DABCO or K2CO3 also gave product 2a

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• -iodosulfone 2a (Table 1). The experiments were conducted at ambient temperature in acetonitrile (0.5 M) and under irradiation by a Kessil lamp at 456 nm. When adding 1,8-diazabiciclo[5.4.0]undec-7-ene (DBU) as sacrificial donor (1 equiv), the desired product 3a was formed in good chemical yield (entry 1

• that DBU was essential for the reactivity, since no reaction occurred in its absence (entry 3, Table 1). Reactivity was also inhibited under an aerobic atmosphere and in the presence of 2,2,6,6‐tetramethylpiperidinyloxyl (TEMPO). These experiments are consonant with the occurrence of a radical

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• photoexcitation of the photosensitizer 43 to form 44 which can oxidize aniline 36a to give radical cation 46 (Scheme 7). Deprotonation by DBU produces the radical 40. The radical anion photosensitizer 45 can reduce Ni(I) to Ni(0), closing the first catalytic cycle. The Ni(0) complex can undergo oxidative addition

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• ][13][14][15] such as NaHMDS, DBU, NaH, DABCO, t-BuOK, aq NaOH but none of them gave the desired product. Instead, either a complex mixture was formed, or the starting material was recovered as such (Table 1). However, when we treated compound (±)-4 with a strong base such as KHMDS (2 equiv) in THF at

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• ketone methylation gave access to 56. Directed C1–C5 vanadium-mediated epoxidation followed by DBU treatment and TBS deprotection afforded 57 in one pot. The tertiary alcohol 58 was obtained as a single diastereomer after hydration of position C18. Subsequent reduction with DIBAL-H gave the desired

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• formation of 5. Known reactions giving 11, and reactions of dihydrolevoglucosenone 12 and aromatic aldehydes with DBU. Reactions of enone 1 and aldehydes promoted by NaOMe in MeOH. Supporting Information Supporting Information File 323: Experimental details for all compounds including 1H and 13C NMR

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• accomplished the synthesis of phosphoric esters through a 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence [43]. A decade later, Chakravarty and colleagues reported the efficient synthesis of organic phosphates from ketones and aldehydes using n-BuLi as

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• DBU is a common strategy for the dehydration of serine and threonine units in peptides [16], but unfortunately the acetylation of 10 failed. Interestingly, the direct treatment of 10 with LiClO4 and DBU under prolonged reaction times (3 days) resulted in the elimination of water. This reaction

• basic treatment with DBU in the last step. This was confirmed by HPLC analysis on a chiral stationary phase, showing that the obtained target compound 4 was nearly racemic (Figure 1A). Because of the configurational instability of 4 under base treatment, we aimed at an approach for the final elimination

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• (Danheiser method [22]) or ethoxalylation [23]. Fortunately, all of the substrates 11a–s were converted cleanly and smoothly over 2–5 days into their diazo derivatives 10a–s using p-(acetamido)benzenesulfonyl azide (p-ABSA) as the diazo group donor [24] and DBU as the base. The yields of diazo compounds 10

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• electrochemistry, NHC instability (and anodic electroactivity) prevented its cathodic generation and subsequent use as catalyst or reagent. Instead, the NHC was generated by chemical deprotonation using a strong base (DBU) and then applied in anodic esterification [30][31][32], and amidation of aromatic aldehydes

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• (methyl)phosphinic chloride (10) with amines generated N-aryl-2-chloromethylphenyl(methyl)phosphinamides 12 in 52–99% yields, which were further treated with DBU in refluxing THF, affording 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 in 40–100% yield (Scheme 3) [23]. This is a general

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• uncoordinated. When State-I was treated with TFA, then the reshuffling of the components afforded the slider-on-deck [Cu(82)(111)2]+ (or [(82)(83)]) and the monoprotonated DABCO (60-H+). Addition of DBU reversed the process. The bipeds in the slider-on-deck systems [Cu(82)(111)2]+ (k298 = 42.2 kHz) and [(82)(83

• )] (k298 = 32.2 kHz) move across the deck 82 and prevent binding of the protonated DABCO at the ZnPor binding sites. Use of the fuel acid 112 or 113 instead of applying the TFA/DBU acid/base combination leads initially to protonation of DABCO but due to the decarboxylation of 114 the resulting strong base

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• other solvents. The results are summarized in Table 1. In our first attempt, DBU or (S)-proline in 5% water, 95% methanol yielded a complex mixture of products that were not easy to distinguish (Table 1, entries 1 and 2). The use of NaHCO3 in 98% water, 2% methanol after 3 hours, produced 14% of the

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• losses during extraction. No reaction was observed in CHCl3 (Table 1, entry 14) or utilizing organic bases (Et3N, DBU) (Table 1, entries 16–18). The efforts to increase the yield of diphenoxyketone 5a using 2 equivalents of phenol (2a) in the reaction with bromopropargylic alcohol 1a (Table 1, entries 8

• that compound 6a is the main intermediate to form phenoxyketones. Next, we carried out the experiment using CO2 gas with DBU as a base. In comparison with reactions without CO2 (Table 1, entries 17 and 18), bromopropargylic alcohol 1a with free CO2 gas in the presence of 100 mol % of DBU and phenol (2a