Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• experiments with human CDA (hCDA), we used deprotected nucleoside Va as a mixture of anomers and converted it to Vb through a four-step one-pot synthesis involving silylation, treatment with oxalyl chloride, ammonolysis and removal of silyl groups. Purified phosphinamide Vb was obtained as a mixture of

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• then telescoped, resulting in a one-pot, two-step synthesis of 3c from 3, with improved operativity and yield (see experimental part). The same strategies were followed for the preparation of 1c (from 1b or from 1), as well as for 4c (from 4b or from 4). The preparation of the tetrabromo compound 2c

• issues observed during the benzylic bromination of 4. As a result, 4c was obtained from 4 (in a one-pot, two-step process) with an 85% isolated yield. The particular cleanliness of the conversion of 4b into 4c, featuring negligible formation of gem dihalides, could arise from the useful steric hindrance

• given by the halogen bound to the core. Figure 4 collects the results obtained in the preparation of aryl-cored halides of Figure 3, by means of the peroxide-bromide process. For products featuring bromine on both the aromatic core and the side chain, the “direct” one-pot two-stage and the “indirect

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• complexes are important for the synthesis of heterocyclic and non-heterocyclic compounds. In 2009, Arthuis and co-workers developed a new process for the synthesis of 2-aroylindoles and 2-heteroaroylindoles by a one-pot palladium-catalyzed domino reaction that involves an initial C,N-coupling followed by

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• Kingdom 10.3762/bjoc.20.82 Abstract 2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form

• acyl fluoride products directly from carboxylic acids. Here, we report the results of this study, which led to the development of a practical and high yielding methodology for the synthesis of acyl fluorides and their subsequent one-pot conversion into amides. Moreover, by virtue of BT-SCF3’s ability

• unreliable isolation of acyl fluoride intermediates, we next considered whether BT-SCF3-mediated deoxyfluorination of carboxylic acids could be coupled with a subsequent acylation in an overall one-pot process. Selecting amines as nucleophilic coupling partners, a short optimisation study was carried out to

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• Chemistry and Center for Green Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA 10.3762/bjoc.20.81 Abstract A new method for the synthesis of heterocyclic systems containing tetrazole and tetrahydroisoquinoline is developed via the performance of one-pot Ugi-azide

• and Heck cyclization reactions. The integration of the multicomponent and post-condensation reactions in one-pot maximizes the pot-, atom-, and step-economy (PASE). Keywords: Heck reaction; one-pot; tetrahydroisoquinoline; tetrazolo-pyrazino[2,1-a]isoquinolin-6(5H)-ones; tetrazole; Ugi-azide reaction

• fused imidazotetrazolodiazepinones (Scheme 2A) [37]. The Gámez-Montaño group introduced a one-pot synthesis of Ugi-azide/N-acylation/Diels–Alder/dehydration reactions for isoindolin-1-one and 1,5-DS-T in a linked manner (Scheme 2B) [41]. The Ding group developed sequential Ugi-azide/Ag-catalyzed

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• carbene insertion into bicyclobutane was reported in 2022 by Bychek and Mykhailiuk [74]. Previously the same group had also reported the synthesis of BCPs containing a difluorinated bridge by CF2 carbene insertion into bicyclobutanes [75]. More recently Davies and co-worker reported the one-pot synthesis

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• salts is an efficient tool for the construction of two or more chemical bonds in a one-pot process. Ortho-functionalized diaryliodonium salts have showcased distinct reactivity in the exploration of benzocyclization or arylocyclization. With this strategy of ortho-ester-substituted diaryliodonium salts

• the low yield of 3al. We subsequently turned our attention to explore the effect of structural diversity of the ortho-ester-substituted diaryliodonium salts. Firstly, a family of substituted diaryliodonium salts were synthesized in a one-pot procedure. These ortho-substituted diaryliodonium salts were

• protocol enables the efficient formation of two chemical bonds in one pot, representing a valuable tool for the synthesis of polycyclic benzocoumarins. Our ongoing research endeavours are dedicated to explore the detailed reaction mechanism with the ultimate aim of broadening the scope and applicability of

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• reported. In surface-mediated reactions, the proton donor is typically Si–OH or Al–OH. For clarity in discussing subsequent reactions, we have separated the in situ HCl gas synthesis from the hydrochlorination. It is important to note that these reactions are one-pot processes rather than two-pot reactions

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• product. Compounds 12 did not tolerate aqueous conditions or high temperatures and have also been observed to degrade under direct sunlight. Next, a stepwise one-pot approach was investigated to increase the overall yield (Scheme 6). The reaction in anhydrous DMF yielded a mixture of the desired product

• the aromatic nucleophilic substitution of 2-azido-4-sulfonylquinazoline 12a or by performing three subsequent SNAr reactions starting from 2,4-dichloroquinazoline 7 in a one-pot procedure [28] (Scheme 9, Table 2). The resulting products exist in an azide–tetrazole equilibrium in solution, but in solid

• . Synthesis of 6,7-dimethoxyquinazoline derivatives 16, 17a and 18. Synthesis of 2-amino-4-azido-6,7-dimethoxyquinazolines 17. Synthesis of terazosin and prazosin hydrochlorides 19a and 19b. Modifications of derivatives 17. Conditions for one-pot synthesis of 4-azido-6,7-dimethoxy-2-sulfonylquinazolines 12

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• ][21][22]. Multicomponent reactions (MCRs) provide one-pot reactions, simple synthetic procedures, less waste being produced, fewer purification steps, and a high atom economy [23]. The GBB three-component reaction is carried out in the presence of Lewis or Brønsted acid catalysis to increase the

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

• data. Further syntheses of spirobutenolides 2 were performed under the one-pot conditions: after completion of the first O–H insertion step, a base was added to the reaction mixture and kept at room temperature until completion of the cyclization step, controlled by TLC. The results of the syntheses

• also in the alpha position of the furanone ring. Reactions with allenic acids 11 were carried out according to a similar scheme, in the one-pot mode, without isolation of OH-insertion intermediates 12 (Scheme 4). In order to accelerate the cyclization step in this case, moderate heating was used after

• 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

(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

• -1,1,1,4,4,4-hexafluorobut-2-enes have been investigated. A simple, one-pot procedure for the preparation of a new allene (1,1,4,4,4-pentafluorobuta-1,2-diene) and some of its transformations is presented. Keywords: allenes; dehydrohalogenation; halogenation; 1,1,1,4,4,4-hexafluorobut-2-enes; isomerization

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

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• his research group developed a novel sulfonic graphitic carbon nitride (g-C3N4-SO3H) as a nanosheet ionic liquid for the one-pot synthesis of BIMs [125]. Graphitic carbon nitride is a non-metal and non-toxic chemically stable nanostructure, which is obtained through a facile pyrolysis process that has

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• -di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4. 6,8-Di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 prepared by the one-pot reaction between 6,8-di-tert-butyl-3H-phenoxazin-3-one (1) and aromatic amines 2b (the yield is given in parentheses). Synthesis of 14H-quinoxaline[2,3-b]phenoxazines 5

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• ; multi-step reactions; multicomponent reactions; one-pot synthesis; organocatalysis; tandem reactions; transition-metal-catalysis; The synthesis of pharmaceutical ingredients, natural products, agrochemicals, ligand systems, and building blocks for materials science has reached a high level of

• atom efficiency, step and pot economies, decreased number of purification steps, or protecting-group-free synthesis. Multi-step domino [1][2] and one-pot [3] reactions represent a new powerful toolbox in organic synthesis to install molecular complexity economically and sustainably, starting from

• simple compounds. In particular, catalytic domino reactions and one-pot processes with excellent selectivity and functional-group tolerance are of significant interest to industrial and academic research. In the so-called domino reactions, all of the required reagents, the catalyst, and a solvent are

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• disaccharide synthesis alongside C6-protected acceptors (2a or 2b in Figure 2) [10][11][14][15][37][38]. More recently, an innovative one-pot glycosylation approach using a (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)-protected glycosyl acceptor has been developed, demonstrating satisfactory stability

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

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

• ; carbonylative cyclization; Chan–Lam; nitrogen heterocycle; one-pot; Introduction Dibenzodiazepine units are without doubt highly privileged structures, endowed with numerous medicinally relevant properties, and notably include anti-anxiolytic and antidepressant activities. These scaffolds have received much

• occurs first at the amide position. This approach enabled the successful synthesis of a broad spectrum of dibenzodiazepinone units in a one-pot fashion. The synthetic utility of Laha’s approach was highlighted by preparing the corresponding dibenzodiazepinone which was further reacted with N

• driving forces for the development of the work discussed in this report. Results and Discussion Synthesis of o-(2-bromophenyl)aminoaniline via Buchwald–Hartwig C–N coupling One-pot synthesis of dibenzodiazepinones Our preliminary attempt to synthesize DBDAPs via B–H amination and carbonylation was carried

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• [24][25]. Interestingly, Jacquemard et al. outlined a useful, mild method for removing a range of carbamates using Bu4NF in an article from 2004 [26]. As 7 contained a DTBS group, the possibility of removing both Troc and DTBS groups in a one-pot procedure was tested. Disaccharide 7 was therefore

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• one-pot transformation from readily available benzyl(prenyl)malonate substrates. After the photooxygenation of the prenyl moiety, the resulting hydroperoxide was directly engaged in a Hock cleavage by adding a Lewis acid. The presence of an aromatic nucleophile in the reaction mixture and that of a

• surrogate readilly unmasked under Hock cleavage conditions. The oxidative cleavage of this alkene would not only release the aldehyde group, but also volatile acetone originated from the traceless isopropylidene motif. Overall, a three-reaction process will thus be performed in one pot (Scheme 1c

• substrates to be submitted to the one-pot tandem transformation (Scheme 5). With only a few exceptions, the presence of ortho (R1), meta (R2), or para (R3) substituents on the benzyl moiety generally allowed the intramolecular Friedel–Crafts reaction, after the first intermolecular one in the presence of

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• , and aryl bromides as bromination reagents are limited. Wan and Li, respectively, demonstrated a few examples of a one-pot N-acylation and C5–H bromination of 8‑aminoquinolines using acyl bromines acting as both acyl and halide donors [25][26]. The groups of Lei and Fang independently realized the

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• cyclopentadiene moieties. TCBD 4, obtained through the [2 + 2] CA–RE reaction, continues to function as an electron-accepting alkene, as shown in Scheme 4. Subsequent [2 + 2] CA–RE reactions involving electron-rich alkynes yield tetracyano-1,3,5-hexatrienes (TCHTs). These reactions occur seamlessly in a one-pot

• one-pot reaction involving TCNE and one equivalent of 3-(4-(dimethylamino)phenyl)propionitrile in toluene at 90 °C for 24 h. Subsequently, one equivalent of 1 was added at 90 °C for 24 h (Scheme 6) [101]. While the separation of the isomers was not achieved, the structure of the 3Z,5E isomer was

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• , this new method creates two C–N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste. Keywords: carbazoles; heteroaromatics; iodanes; metal-catalyzed; one-pot reaction; Introduction N-Acyl carbazoles are effective

• followed by a ring-closure starting from 2,2'-diiodo-1,1'-biphenyls [15][16][17]. Related one-pot procedures are also described (Scheme 1b) [18][19]. Such 2,2´-dihalobiphenyls are established starting materials for synthesizing a variety of heterocycles. Usually, their utilization leads to the production

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

• the PCR assembly step. Because of this, misalignments may occur, and errors may be introduced. (2) PCR assembly of multiple short ODNs in one pot requires similar melting points of the multiple overlapping regions of the short ODNs. Therefore, the sequences of the short ODNs must be carefully chosen

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• NHC·CS2 zwitterions relies on the deprotonation of an azolium salt with a strong base, typically potassium tert-butoxide or potassium bis(trimethylsilyl)amide (also known as potassium hexamethyldisilazide, KHMDS) followed by the addition of carbon disulfide either in one pot or after the isolation of the