Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• ]. In the presence of a Lewis base, MBH carbonates of isatins can be easily converted to activated allylic ylides, which in turn can undergo allylic substitution and annulation reactions to give diverse 3-substituted and spirooxindole derivatives [36][37][38][39][40][41]. Inspired by these elegant

• and were fully characterized via various spectroscopy methods. The further annulation reaction did not proceed under the reaction conditions. The similar reaction of triphenylphosphine and MBH maleimides of isatins also resulted in the corresponding triphenylphosphaneylidenes 6e and 6f in satisfactory

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• presented above, the substrate range of the TBAl-catalyzed sulfenylation/annulation reaction between different arylated enaminones and sodium p-tolylsulfinate was subsequently investigated, and the corresponding results are shown in Scheme 3. From the results, both electron-withdrawing and electron-donating

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• moiety of the amide group resulted in pyrimidone annulation [41]. This was observed for the first time and completed the reported heteroannulation landscape utilizing the Niementowski reaction [25]. In general, the reactions had a rather broad scope as a great range of cyanoacetamides was compatible. The

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• Cu-catalyzed electrochemical C–H activation strategy through C–H alkynylation of arylamides followed by electrooxidative cascade annulation (Figure 4) [48]. This reaction enables sustainable C–H functionalization by utilizing electricity as the terminal oxidant instead of stoichiometric amounts of

• desired annulation products. Moreover, the same products were generated using alkynyl carboxylic acids instead of terminal alkynes via decarboxylative C–H alkynylation and annulation. Cyclic voltammetry (CV) studies exhibited an oxidative current at 0.95 V vs SCE in the presence of the Cu(II) salt, base

• (KR) of the racemic ketimine ester, providing the same chiral product 35 with recovered enantioenriched starting material. Additionally, when a 1-naphthyl ester was used instead of a methyl ester at −10 °C, 1,4-addition followed by intramolecular tandem annulation generated the corresponding chiral

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• the coupling with copper triflate as catalyst, without ligand, co-catalyst or other additives. The reaction involved the formation of the imine XVII followed by alkynylation to propargylamine XVIII, cyclization, and oxidation to quinoline 23 (Scheme 17) [34]. Three component oxidative annulation to

• -methylthiazole-2-carboxaldehyde as chelating agent, in the presence of copper triflate and the chiral diamine ligand 28. The stereoselectivity was directed by the formation of a proposed catalyst complex 29 involving two molecules of Schiff base (Scheme 22) [39]. The three-component annulation of aldehydes

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• ) annulation of enals with ynamides 8 to afford axially chiral 7-arylindolines 9 was reported [20]. The reaction mechanism, rationalized by DFT calculations, is believed to occur through catalyst C3 activation of the substrate 8, dehydration, and deprotonation with tautomerization leading to the enamine

• -catalyzed (3 + 3) annulation [29]. A broad scope was demonstrated, comprising more than 50 diversely substituted compounds (Scheme 10). Wong, Zhao, and co-workers disclosed the intriguing formation of bridged biaryls featuring eight-membered lactone rings 32 [30]. This serendipitously discovered

• followed by lactonization to Int-21 and Int-22 (Scheme 11c). Chi and co-workers showed that desymmetrization of urazoles can lead to axially chiral derivatives [31]. The NHC-catalyzed (3 + 2) annulation between α,β-unsaturated aldehydes 36 and urazoles 37 generates atropoisomers 38 with a C–N stereogenic

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -catalyzed annulation reaction between bromo-chloronaphthalene dicarboximides 6 and heteroarylboronic esters that enabled the syntheses of acenaphthylene-fused thiophene and indole derivatives 7 having donor-acceptor units (Scheme 1a) [40]. In 2021, Jin and co-workers developed an elegant Pd-catalyzed

• reaction cascade starting from diarylalkynes 8, which involves indole formation/peri-C–H annulation and N-dealkylation reactions to afford acenaphthylene-fused indole products 9 (Scheme 1b) [41]. Recently, Takeuchi and co-workers reported an effective Ir-catalyzed [2 + 2 + 2] cycloaddition between 1,8

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• subsequent second annulation, yielding a new series of extended polyaromatic mesomorphic compounds, i.e., 1,1',3,3',4,4'-hexafluoro-6,6',7,7',10,10',11,11'-octaalkoxy-2,2'-bitriphenylene (Gnm) which were found to display a Colrec mesophase. The specific nucleophilic substitution patterns of the Fn

• enables to exploit further the SNFAr procedure, as demonstrated for 4F-TPn and 6F-BTPn [44], through a subsequent second annulation reaction. This results in a second series of extended π-conjugated aromatic mesomorphic compounds, 1,1',3,3',4,4'-hexafluoro-6,6',7,7',10,10',11,11'-octaalkoxy-2,2

• prepared in high yield via FeCl3-oxidative coupling of 1,2-dialkoxy-4-bromobenzene (Scholl reaction). The new triphenylene derivatives, F3–F12, were prepared in moderate to high yields (51–73%). In addition, three bitriphenylene derivatives were synthesized in a subsequent annulation step from Fn

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• evaluate the synthetic utility of this methodology, derivative 39e was reduced using BF3·OEt2 and Et3SiH leading to 41 in a good yield and moderate diastereoselectivity (Scheme 14). In 2017, Li’s group developed a chiral (DHQ)2PHAL-catalyzed [2 + 4] annulation reaction of cyclic 1-azadiene 14 with γ-nitro

• Mannich-type reaction of isocyanoacetates with N-(2-benzothiazolyl)imines. Enantioselective modified cinchona alkaloid-catalyzed [4 + 2] annulation of γ-butenolides and saccharin-derived 1-azadienes. Chiral tertiary amine-catalyzed [2 + 4] annulation of cyclic 1-azadiene with γ-nitro ketones. Inverse

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• , 98160, México 10.3762/bjoc.20.256 Abstract A series of 1,5-disubstituted tetrazole-indole hybrids were synthesized via a high-order multicomponent reaction consisting of an Ugi-azide/Pd/Cu-catalyzed hetero-annulation cascade sequence. This operationally simple one-pot protocol allowed high bond-forming

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• -workers reported a one-pot three-component reaction (3-CR) of sulfamate‐derived cyclic imine, isocyanide, and acetylenedicarboxylate. In this reaction too, the pyrrole-fused sulfamate is synthesized through intermediacy of the in situ-formed zwitterion II and [1 + 2 + 2] annulation reaction (Scheme 1b

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• ’ steric demand as seen with compound 11 with opposing bromines, coupled with the added complication of being a rotameric mixture, as well as adjacent hindrance of the nearby β-ethyl groups. Examples of palladium coupling on ‘opposing’ halogen atoms can be seen in the annulation of vic-bis(pinacolatoboryl

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• reaction. Therefore, they believe that the dearomatization caused by copper vinyl allenylidene intermediate remains a key step in the reaction (Scheme 30). Copper-catalyzed yne-allylic substitution–annulation reactions In the pioneering report [62], Fang et al. found that when cyclic 1,3-dicarbonyls such

• + 2] cyclization of yne-allylic esters and 2-naphthalenols, resulting in a range of allenyl dihydronaphthofuran products with high diastereo- and enantioselectivities (Scheme 34, 32a–h). The attempt to separate the intermediate before cyclization failed, indicating that the following annulation and

• ). Preliminary mechanistic studies have ruled out the 1,3-sigmatropic shift, indicating that the reaction proceeds through a nucleophilic substitution–annulation process of a reactive π-extended copper-allenylidene intermediate (Scheme 43). At the same time, Qi and Xu et al. [79] also realized the dearomative

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• successfully synthesized on a gram scale through a three-step reaction sequence. The process began with 2,6-diisopropylphenylamine, which underwent alkylation, formylation, and substitution reactions. The carbene synthesis was then achieved via a two-step process involving ynamide annulation, followed by

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• devoted to the synthesis of this core structure and, to the best of our knowledge, only one molecule of this type was obtained in low yield as a secondary product during studies on the use of the Friedländer annulation reaction starting from naphthylamines [12]. Therefore, the goal of this paper is to

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• , showcasing 118 examples with good to high yields. The LSF of complex molecules, such as probenecid and estrone, highlighted the potential application of this method in the synthesis of selenium-containing drugs (Scheme 19). 1.1.3 Annulation. Annulation refers to the formation of rings, a process that

• involves building a ring onto a preexisting system, whether cyclic or non-cyclic. The Lei group developed an electrooxidative annulation reaction that facilitates LSF [28]. A regio- and stereoselective protocol was established for the [4 + 2] annulation of indole derivatives, allowing access to highly

• ] annulation of hydroxamic acids 54 with alkenes for approaching benzo[c][1,2]oxazines [30]. This method successfully achieved the LSF of several natural products such as lithocholic acid and estrone, affording the following benzo[c][1,2]oxazine derivatives in moderate to good yields (Scheme 22). The

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• screening approaches [107][144][145][146][147]. Thereby, experimental efforts can be focused on the most promising candidates predicted by the model. Denmark and co-workers utilised such an approach to design highly selective catalysts for a peptide-catalysed annulation reaction [68]. Using conformer

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• , curcumin showcases its Michael donor–acceptor ability in different ways, such as simple Michael addition, [4 + 2] annulation, Michael addition followed by cyclization or one-pot multicomponent reactions (MCR), etc. (Scheme 1) [25]. In 2011, our group reported the reactivity of curcumin as a Michael donor

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• isoquinolinone derivatives. The method provides highly chemoselective access to 3- or 4-substituted isoquinolinone derivatives by reacting o-alkenylbenzamide derivatives with PISA in either acetonitrile or wet hexafluoro-2-isopropanol. Keywords: annulation; C–H amination; hypervalent iodine reagent; iodine(III

• nonmetallic reagents as an attractive alternative is less developed. In 2014, Antonchick and Manna firstly reported the synthesis of a series of 3,4-diaryl-substituted isoquinolinone derivatives through oxidative annulation between alkynes and benzamide derivatives using iodobenzene as a catalyst and

• option for the preparation of isoquinolinone derivatives. In 2020, two reports have been published on the conversion of alkyne-tethered N-alkoxybenzamides to isoquinolinones by intramolecular oxidative annulation, either electrochemically or using the hypervalent iodine reagent phenyliodine(III

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

• (IPT)-mediated intramolecular oxidative annulation and a hydroxylamine-induced ring cleavage of intermediate 48. With this one-pot sequential procedure they synthesized 49 in yields up to 95% (Scheme 19). The subsequent GBB-3CR led to the unique 1H-imidazo[1,2-a]imidazole core 50 with 4 distinct

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• , and contain nitrogen, boron, oxygen, and sulfur atoms. Using these building blocks, we generated a chemical library of cata-condensed hetero-PASs (cc-hPASs) ranging in size from 3- to 10-ring systems, by combining the rings according to the annulation types shown in Figure 1B. The number, type, and

• and composition and therefore have varying numbers of atoms and π-electrons. We plotted the KDE distributions of the HOMO, LUMO, and Gap for this subset of data, colored according to the longest linear stretch in the molecules (Figure 5A). Note that, for cc-hPASs, a linear annulation is defined as

• three consecutive rings having an angle of 180° between the ring centroids; any angle that is not 180° is considered to be an angular annulation (see Figure 1B). Indeed, although a trend may be observed, it is not nearly as pronounced as the trend we observed for the cc-PBHs in COMPAS-1 [6]. This led us

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• -) derivatization of aromatic scaffolds because it can be exploited to stabilize the longer (hetero)acenes. In contrast to cata-benzannulation, cata-imide-annulation does not perturb aromaticity patterns and further introduces inductive stabilization of frontier MO levels, which has enabled the production of n-type

• cyclic imides (Table 1). Overall, however, the cata-annulation does not lead to substantially different electrochemical behavior, which is encouraging because we had anticipated that the deflection away from planarity caused by adjacent placement of cyclic imides might adversely affect extent of π

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• intermediates through selective FeCl3-catalyzed intramolecular N-annulation. Keywords: α-aminoacetals; fused-ring systems; heterocyclic hemiaminals; heterocyclic N,O-aminals; multicomponent reactions; Introduction N-Fused heterocycles are ubiquitous within crucial molecules, including biologically active

• -hydrazino form [17][24][25], we conceived the idea of reversing the reactivity of 4a–r in the six-membered cyclization process (N- vs O-annulation) through the generation of an electrophilic oxocarbenium [26][27] cation intermediate from the acetal residue at N-3 of the (thio)hydantoin core. To pursue our

• process and developed a catalytic system-controlled selective intramolecular N-annulation process for ring-fused biheterocyclic N,O-aminal derivatives as stable imine equivalents and useful tools for new bond formation in view of further fused-heterocylization processes. Moreover, control experiments

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• + 2] annulation reactions [68][69][70]. This study was the first to evaluate the performances of sunflower seed oil (SSO), olive oil (OO), oleic acid (OA) and lauryl myristate (LM) as green solvents in the well-known intramolecular Diels–Alder furan (IMDAF) reaction between aminofuranes and maleic

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• either annulation of an isoxazole fragment to a pyridine cycle or vice versa formation of a pyridine ring based on appropriately substituted isoxazoles. In the first case (Scheme 1A) 3-halo- [11][15][16][17][18][19] or 3-hydroxypyridines [8][20] bearing a suitable functionality in position 2 were used

• molecule is not shown), 13c (top right), and 13d (bottom) with thermal ellipsoids set at a 50% probability level. Intermolecular hydrogen bonds are drawn with dashed lines. Methods for the synthesis of isoxazolo[4,5-b]pyridines: (A) annulation of an isoxazole fragment to a pyridine ring; (B) annulation of