Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• controlling the formation of undesired byproducts during its reactions. This review explores alternative C1-building blocks that serve as surrogates for formaldehyde, aiming to mitigate some of the challenges associated with its use in multicomponent reactions. By identifying these alternatives, toxicity

• devoted to dimethyl sulfoxide, dihalomethanes, hexamethylene tetramine, and glyoxylates as C1-building blocks, substituting formaldehyde. Review Methanol as a source of formaldehyde There are several reports on the use of alcohols under oxidative conditions as aldehyde surrogates in Ugi and Passerini

• et al. developed a three-component Mannich-type reaction under oxidative and catalytic conditions that allows the coupling of aryl ketones 18 and saccharine (19) using DMSO as the solvent and the source for a methylene bridge linking the two building blocks (Scheme 15) [49]. Following this strategy

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• macrolactamisation [21]. The syntheses of required unit A [28], C [29][30], and D [31] building blocks were accomplished as described previously. tert-Butyl-protected leucic acid 14 and Fmoc-β-aminopivalic acid (15) were connected by Steglich esterification (Scheme 2) and after cleavage of the tert-butyl ester group

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• inductive methylation [24]. To research further the bioactivity of the pheromone, herein, we report an effective synthesis of the aggregation pheromone of T. castaneum, which uses the cheap (R)- and (S)-2-methyloxirane as chiral sources, connects two chiral building blocks through Li2CuCl4-catalyzed

• ]. Similarly, chiral tosylate (R)-10 could be prepared from (S)-2-methyloxirane ((S)-2) through the ring-opening reaction, tosylation, stereospecific inversion, hydrolysis, decarboxylation, reduction, and second tosylation (Scheme 3). With two the chiral building blocks (R)-10 and (S)-10 in hand, we next

• the aggregation pheromone (4R,8S)-1, (4S,8R)-1, and (4S,8S)-1 were prepared through Li2CuCl4-catalyzed coupling and oxidation with RuCl3/NaIO4 from chiral building blocks (R)-10, (S)-10, (R)-11 and (S)-11, which were characterized by NMR spectroscopy and HRMS. Conclusion In summary, we have achieved a

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• substitution. Substituents such as halogen atoms must be introduced into the N-acetyl diazocine structure during the synthesis of the building blocks. In the present work we start from mono- and dihalogenated N-acetyl diazocine 2–4 (Figure 2) and focus on the further derivatization via cross-coupling reactions

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• glycochemists. The protecting building blocks on the glycosides contribute significantly in attaining the required stereochemistry of the resulting glycosides. Strategic installation of suitable protecting groups in the C-2 position, vicinal to the anomeric carbon, renders neighbouring group participation

• huge interest in the study of ‘Glycomics’ or ‘Carbohydrate Chemistry.’ These truly elevated the recognition of carbohydrates from being mere building blocks to a frontier research topic towards the development of drugs and pharmaceuticals [12][13], diagnostic tools [14], artificial sweeteners [15

• are various studies both supporting and refuting the concept of long-distance participation of building blocks. We will first give an overview of how neighbouring group participation of different protecting groups affects the stereochemistry of the glycoside bonds followed by the role of the same

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• ; Introduction 1,2-Benzoquinones represent unique building blocks for various classes of heterocyclic systems. Their structure depends on the reactivity of the initial heterocycles and 1,2-benzoquinones, as well as on the reaction conditions. In the series of 2-methylquinolines [1], 2-methylquinoxalines [2], 2

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

• have made them to become valuable building blocks in organic synthesis. Nucleophilic additions or spiroannulation of the highly reactive carbonyl group at the C-3 position of isatins have various fascinating applications in organic synthesis, which allowed transformation of isatins into various

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• coupling of alkyne 8, THIQ segment 9, and benzaldehyde would enable convergent assembly of the building blocks to produce 10 [43][44][45][46]. Removal of the cyclic acetal in 10 followed by Strecker-type conversion leading to an α-amino nitrile would enable tandem intramolecular cyclization with phenol to

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

• utilized numerous times in medicinal chemistry campaigns as hits, leads and eventually even drugs, such as 2-aminothiophenes, -quinolines and -indoles [42][43][44][45]. Synthetic exploitation The synthesis of the key cyanoacetamide building blocks was our primary objective. In a parallel setup, a variety

• Gewald three-component reactions. Our focus was to create a representative, diverse and structurally complex library of building blocks, covering a range of shapes and chemical spaces, to facilitate formamide-based heteroannulation for the synthesis of the desired adducts. Thus, we employed aliphatic and

• anthranilic acid and B) access to heteroannulated pyrimidones by MCRs of suitably substituted heterocycles and formamide as C1 source. Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Diversity and complexity were the essential features of our library of starting

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• polymerization concentration of 17 μM. These polymers were highly concentration-dependent. Establishing this new dimerization motif with shape-persistent H-bonded macrocycles widens the scope of noncovalent building blocks for supramolecular polymers and augurs well for the future development of functional

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• properties. Moreover, these materials offer versatility in their synthesis, allowing for the incorporation of various building blocks to tailor the polymers to desired specifications. Additionally, they lend themselves well to the synthesis of block copolymers, further expanding their potential applications

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• ]. These are three-dimensional molecular nanocarbons that include heptagons [10][11][12][13][14], octagons [15][16][17][18], or even larger carbocycles. In theory, these fragments can serve as building blocks in a bottom-up approach to constructing carbon schwarzites [19][20]. To validate this concept, we

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• building blocks like organohalides can be converted into alkyl radicals by means of photoinduced silane-mediated halogen-atom transfer (XAT) to offer a mild and straightforward methodology of alkylation. In this research, we present a metal-free strategy for the photochemical alkylation of dehydroalanine

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• -carboxylic acid derivatives are not only valuable synthetic building blocks [3][4][5][6][7][8][9][10][11] but also show useful biological activities [12][13][14][15][16][17][18]. Although many 2,2-bifunctionalized azirines have been synthesized [3][4][5][6][7][8][9][10][11], the synthesis of only one 2H

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• carbazate (NH2-NHCbz/NH2-NHBoc) were chosen as starting materials in order to obtain final building blocks suitable for peptide synthesis. While the synthesis of compound 3a was already reported [28], compounds 3b–f are not described in the literature. All the fluorinated hydrazones were obtained in good

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• ] developed artificial, ‘natural-like’ polyphenols, using the Ugi reaction, since it leads to mixed polyphenol–peptidomimetic structures (Scheme 4). The procedure involved an Ugi reaction using phenolic building blocks protected as allyl ethers, followed by deprotection, acetylation, and high-yielding

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• , including ligand coupling, oxidative addition, intermolecular nucleophilic attack, 1,2-aryl migration, reductive elimination, and intramolecular nucleophilic attack. This approach offers a rapid and effective way to produce 5-fluoro-2-aryloxazoline compounds, which are valuable building blocks in organic

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• or transform into a long-lived radical cation by substrate reduction, which are the fundamentals of photoredox catalysis (Figure 13a). Monomeric porphyrins and supramolecular porous frameworks composed of porphyrin building blocks, such as metal-organic frameworks (MOF) and covalent organic

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• ; Introduction Enantioenriched α-allenic alcohols are an important class of chiral building blocks used for the chemical synthesis of biologically relevant molecules [1][2][3][4][5]. Their strength comes from the rich synthetic versatility [6][7][8][9] and biological relevance [10] of the allene functionality

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• corresponding nucleic acid sequence. Proteinaceous enzymes then go on to catalyze biosynthetic reactions that put together small molecule building blocks (BB) to generate natural products with extremely diverse chemical structures. Because the intricacy of this process is not fully understood, scientists still

• NRP. AntiSMASH is freely available for the research community worldwide [61]. Underexplored and oversampled NRP building blocks With these prediction tools at hand, it became possible to survey the biosynthetic diversity of NRPs from a new perspective. Specifically, Jian et al. compiled data in

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• interactions in the nonplanar pyrindanes 1. The obtained compounds 1, having a 2-chloropyridine-3,4-dicarbonitrile moiety, contained easily modifiable functional groups [48][49][50][51][52][53][54][55]. This qualified compounds 1 as promising building blocks for diversity-oriented synthesis [56][57] and for

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• preparation and host assembly. The synthesis adheres to a two-synthon approach which relies on the connection of two building blocks through a CuAAC click reaction (Scheme 1). Building block S1, the azide, is not modified in this work and the preparation is achieved with an overall yield of 43% via the

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• –CH2–(CF2)n–COOCH3) with triflate as leaving group in terminal position are easily accessible and versatile building blocks for attaching long chain acids (pKa 0–1) to substrates in Williamson ether-type reactions. Keywords: acid-functionalized porphyrin; electron-rich porphyrin; nickel porphyrin

• -triflated, perfluoroalkylated carboxylic acids 16, 17, and 18 are easily accessible and versatile building blocks for connecting long chain acids (pKa range between 0 and 1) to substrates in Williamson ether-type reactions. Synthesis of the starting materials 16, 17, and 18 for the subsequent Williamson

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• remarkable stereoselectivity, a finding elucidated by DFT analysis. These results mark significant progress toward the synthesis of novel fluorinated building blocks. Our team is currently exploring the application of this methodology to amino acid substrates, aiming to contribute further to the burgeoning

• our laboratory, we have explored the synthesis of 3,3,3-trifluoro- and 2,3,3,3-tetrafluoro-N-substituted propanamides, contributing to the field of fluorinated amides [25]. We have also investigated deprotonation at the α position of other fluorinated carbonyl derivatives as a route to new building

• blocks [26]. Despite the known instability of trifluoromethylated carbanions [27], their catalytic application has yielded valuable products [28][29][30]. gem-Difluoroalkenes and trifluoroalkenes are excellent acceptors in the Michael addition reactions. There are also known examples of the use of gem

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• /Education Center for Excellence in Molecular Sciences Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China 10.3762/bjoc.20.242 Abstract The selective C–H trifluoromethylthiolation of aldehyde hydrazones afforded interesting fluorinated building blocks, which could be used as a