Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• compound 57 was obtained by treating hypervalent iodine salt 56 with NaNO2 in the presence of DBU as the base (Scheme 23). This salt was also studied for the arylation of sulfur, oxygen, and carbon giving good yields of corresponding products [74]. O-Arylation Arylation of oxygen is a significant chemical

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• Science and Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki 316-8511, Japan 10.3762/bjoc.20.233 Abstract Treatment of various (R)-N-(2,2,3,3-tetrafluoropent-4-en-1-ylidene)-1-phenylethylamine derivatives with 2.4 equiv of DBU in toluene at room temperature to 50 °C for 24 h led to

• the NOESY spectrum of the imine (R)-16c, the stereochemistry of the imines (R)-16 was determined as E [36]. Among the imines thus obtained, (R)-16b was used to investigate the optimum reaction conditions (Table 1). Treatment of (R)-16b with 1.2 equiv of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in THF

• diethyl ether, toluene, hexane, and cyclohexane, (S)-20b was obtained in 30% to 40% yield and significant amounts of unreacted substrate were still observed, although formation of the byproduct 22b could be generally suppressed. We also examined the reaction using other bases instead of DBU. As shown in

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• , entry 10). Other bases like NaOMe, triethylamine, DBU, DMAP, sodium acetate, or DABCO also produced the product in moderate to good yields (42–87%) when used in excess (Table 1, entries 11–16). Interestingly, the reaction did not proceed in the presence of pyridine as a base (Table 1, entry 17). Finally

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• fragment in the side chain were investigated. It was shown that the studied process leads to substituted tetronic acids bearing a pyrrolidinone moiety. The application of 1,1′-carbonyldiimidazole and DBU is necessary for implementation of the considered reaction. Based on the performed research a general

• only in the presence of a strong base (DBU). Results and Discussion The starting allomaltols 3 bearing an amide fragment in the side chain were prepared by reaction of dihydropyranones 5 with appropriate amines 6 applying the previously described method [33][34] (Scheme 2). At first, amide 3a was

• bases under conditions described earlier for corresponding hydrazides. So, among the employed basic agents (Et3N, DABCO, DBU, DMAP, K2CO3, AcONa) only in the case of DBU the expected recyclization was observed and the target product 4a was obtained in 15% yield. In order to enhance the yield of compound

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• possibly due to the higher steric congestion by the selection of the other CO2Et moiety. As shown in entries 8 or 9 in Table 4, it was proved that the usage of tetramethylguanidine (TMG) or DBU as the base provided a different stereoisomer as the major component. For the confirmation of its stereostructure

• , the isolated inseparable mixture of anti,syn-7a and -7b by the reaction of 2b and diethyl malonate was treated with an equimolar amount of DBU in DMSO (rt, 3 h) to furnish products which were identical to the ones obtained in entries 8 or 9 (Table 4). The relative stereochemistry of the isomerized

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• conditions (Table 1, entry 9). Other organic nitrogenous bases were tested (Table 1, entries 10–12). Et3N gave nearly the same result, while DBU seemed less efficient. The use of the inorganic base K2CO3 resulted in poor outcomes. With the optimized conditions in hand, a scale-up was successfully performed

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• diazo precursor. To achieve this, cholesterol was first esterificated using 2-(4-methoxyphenyl)acetic acid and DCC. The resulting arylacetic ester 12 was then reacted with 4-acetamidobenzenesulfonyl azide (p-ABSA) and DBU in anhydrous acetonitrile to yield the diazo compound 13 in 22% yield. The carbene

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• afforded higher yields and shorter reaction times compared to standard stirring conditions with DBU. When employing substrates bearing secondary benzylic sites in the reaction conditions, the difluorinated products were observed exclusively in high yields. In 2016, Britton and co-workers reported a method

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• (Table 1, entry 2). It should be noted that application of strong base DBU led to the complex mixture of products (Table 1, entry 5). At the same time basicity of NaHCO3 is not enough for realization of the studied recyclization and in this case the starting hydrazone 3b was isolated unchanged (Table 1

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• example, methyl acetoacetate (2a) possesses one CH-acidic methylene carbon which can be deprotonated in equilibrium by weak organic bases, such as triethylamine, piperidine or DBU, under thermodynamic conditions. Dimethyl acetone-1,3-dicarboxylate (3a) contains even two reactive methylene groups which can

• of DBU afforded furo[3,2-b]chromen-9-one 36a in 32% yield. Based on this observation, the two-step one-pot reaction of ketoamides 34a–f with 3-halochromones 15a–c was studied which afforded furo[3,2-b]chromen-9-ones 36a–f, albeit, in only low to moderate yields (Scheme 19) [41]. The formation of

• attack of the sulfur to the bromide (intermediate AC) and subsequent ring-cleavage. In most reactions, DBU was employed as the base. In case of products derived from N-unsubstititued 3H-indole-2-thiones (R3 = H), employment of potassium carbonate proved to be advantageous. Similarly to the formation of

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• Foundation (DBU, Ph.D. fellowship to T.J.B.Z., grant number 20022/028). M.S. is grateful to the Chemical Industry Funds for a Kekulé fellowship.

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• %). Under these conditions, the 5-endo-dig cyclization leading to the target spirobutenolide 2a proceeded rather slowly (about 25% conversion per day). However, an attempt to accelerate the reaction by using a stronger base (DBU) resulted in side processes with the formation of unwanted impurities, whereas

• monitor the progress of the reaction and the formation of the OH-insertion product 14. An attempt to carry out the second step in a one-pot format with the addition of 1.2 equiv of base (DIPEA or DBU) was unsuccessful and the formation of the spirocyclic product was not observed. Replacing DCM with a more

• polar solvent, acetone, significantly accelerated the cyclization process. Thus, one to three days were required to complete the 5-exo-tet cyclization process in the acetone/DBU system. The results of the syntheses carried out with the participation of various DAS 1 to obtain spirocyclic THFs are

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• of stereoisomers in 2:1 ratio. After isolation by distillation, 2,3-dibromo-1,1,1,4,4,4-hexafluorobutane (2) was characterized by 1H, 19F, 13C NMR and mass spectra. We studied the reaction of dibromoalkane 2 with various bases such as DBU, Hünig’s base (iPr2NEt), and potassium hydroxide (Table 1). In

• ca. 11 Hz for (E)-isomer). The best results were obtained in Et2O with Hünig’s and DBU bases (Table 1, entries 2 and 3), but unfortunately in these cases the product olefins could not be separated from Et2O. Therefore, we decided to use high-boiling diglyme instead of ether. The reaction of a butane

• 2 with one equivalent of DBU (Table 1, entry 4) led to the same results as for the Hünig’s base (Table 1, entry 1). The use of two equivalents of DBU (Table 1, entry 6) led to the complete conversion of the initial substrate, but the selectivity of the reaction was significantly reduced in this case

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• derivatives (Scheme 1b) [21]. In the course of this reaction 20 mol % of Pd catalyst, 50 mol % of phosphine ligand and 30 equiv of DBU as base were used to afford the desired fluoranthene derivatives. 1-Naphthylboronic acid and 1,2-dibromobenzene in the presence of Pd2(dba)3 (20 mol %) and PCy3 (80 mol

• %) using again a large excess of DBU base (7 equiv) also allowed to prepare unsubstituted fluoranthene in 87% yield (Scheme 1c) [22]. The reaction of naphthol with aryl bromides followed by nonaflation and intramolecular C–H activation for the access to fluoranthenes has also been reported [23]. Most of

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• , did not provide any improvement of the reaction outcome as only traces of the intermediate 3a were obtained (entry 3, Table 1). Switching to DBU as the base under these conditions, gave intermediate 3a in 35% yield (entry 4, Table 1). In fact, DBU was previously shown by Wannberg and Larhed to be an

• . However, we only obtained traces of intermediate 3a (entries 5 and 6, Table 1). A slight improvement of the yield of the intermediate 3 was obtained when using DBU in dioxane, which gave 3a in 42%, but only traces of the target DBDAP were observed (entry 7, Table 1). The difficulty encountered in the

• formation of DBDAP, prompted us to test alternative CO surrogates. When the reaction was performed using Co2(CO)8 (0.3 equiv) in the presence of DBU, the intermediate 3a was isolated in 35% yield, but again no DBDAP 4 was obtained (entry 8, Table 1). Formic acid, an effective CO surrogate [20][22], was also

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