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

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

• synthesis of indirubin-N-glycosides containing the carbohydrate moiety located at the amide-type nitrogen. Isatin-N-glycosides 16 were used as key building blocks. The reaction of ʟ-rhamnose (4c) with aniline afforded N-glycosyl aniline 4d which was acetylated to give 4e (Scheme 12) [22]. The AlCl3-mediated

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

• and 3 as new fluorine-containing building blocks. Experimental General information 1H NMR, 19F NMR, and 13C NMR spectra were recorded on JEOL ECZ 400S spectrometers. Chemical shifts of 1H NMR are reported in ppm from tetramethylsilane (TMS) as an internal standard. Chemical shifts of 13C NMR are

• -containing building blocks. Optimization of reaction conditions for Suzuki–Miyaura cross-coupling using multihalogenated vinyl ether 1a. Optimization of reaction conditions for Sonogashira cross-coupling using multihalogenated vinyl ether 1a. Cross-coupling reactions between multihalogenated vinyl ethers 1

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

• cathodic reduction and to prevent the reoxidation of the reduced SO2 at the anode, a divided cell setup is required (Scheme 12). C–H bond halogenation: Aryl and alkyl halides are important synthetic building blocks for cross-coupling reactions as well as bioactive molecules with applications in

• derived from the interaction of non-activated alkenes with thianthrene [24]. This procedure has the advantage of separating the oxidative activation of the alkenes from the aziridination step, allowing efficient access to a variety of aziridine building blocks containing sensitive functional groups. This

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• unique bowl-shape structures and self-assembly in solution have facilitated their widespread use as building blocks in nanomaterials [61][62]. Nevertheless, precisely due to their vast number of applications, functionalized resorcin[n]arenes are needed that meet the needs of the desired function. For

• chloro species and flattened cone or boat for 1s [89]. Overall, access to electron-deficient and halogenated resorcin[4]arenes in one synthetic step provides building blocks to advance a wide range of chemical, physical, materials, and supramolecular applications. Future modifications of the protocol

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

• 2 were recognized as versatile building blocks for the construction of 2-amino-3-hydroxypropanoates with 2,3-anti stereochemistry, if appropriate amines work nicely in a nucleophilic manner [44]. After the brief optimization of the conditions for the reaction of 2b and p-anisidine, good yields with

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• . 1,2,5-Oxadiazoles (furazans) and their N-oxides (furoxans) are important representatives of nitrogen heterocycles due to their wide applications in various fields of medicine, chemistry, and materials science [6][7]. For example, these heterocycles serve as valuable building blocks for the synthesis of

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• (MCRs) are one-pot reactions that utilize three or more readily available starting materials [1][2][3][4]. Typically, MCRs use reactive functional groups such as ketones or aldehydes, carboxylic acids, amines, and isocyanides where these simple building blocks can be utilized to form large libraries of

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• also been proposed [19][20]. Thus, the synthesis of fluorinated compounds is an active research field. Among these compounds, skeletons bearing CF2 units are important [21][22][23][24], because such molecules can change the physical properties and biological activity. They can also serve as building

• blocks for further transformations. We have focused on the investigation of gem-difluorination of carbon–carbon triple bonds, because this procedure is one of the most simple but powerful and straightforward methods. In addition, there have been a few reports in the literature that seem to mainly rely on

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• ) demonstrates the synthetic utility of the developed method. Keywords: aniline; benzannulation; condensation; 1,3-diketone; Hammett constants; terphenyl; Introduction The aniline moiety is omnipresent in the synthetic chemistry with applications ranging from building blocks to catalysis [1][2][3][4]. Among

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• cytotoxic effects but showed no activity. A number of natural products seem to be produced by reaction of altenuene diastereomers (or of related compounds) with C3 building blocks, i.e., with lactic acid, pyruvic acid, or with acetone (Figure 17). Alternatain D (65) was isolated from Alternaria alternata

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• original Biginelli reaction shown in Scheme 1A was significantly extended by variation of the 1,3-dicarbonyl-containing building blocks. Many groups have elegantly demonstrated the synthetic versatility of numerous enolizable carbonyl components, including β-keto esters, cyclic/acyclic β-diketones, β-keto

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• has organic building blocks, both condensation [98] and post-synthetic modification [99] methods can be used to immobilise organocatalysts. Asymmetric organocatalysis is commonly achieved by pyrrolidone ligands, with great results in a variety of reactions, such as Michael [100] and aldol [101

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• determinants that govern specific molecular interactions. Keywords: computational tools; glycan–protein interactions; MD; molecular recognition; Review Introduction Carbohydrates also referred to as saccharides, sugars, or glycans, constitute one of the main building blocks of biomolecules, alongside lipids

• using the doglycans.py tool. (https://bitbucket.org/biophys-uh/doglycans/). 2. Glycam-Web carbohydrate builder [50]: Free online web-service that gives the possibility to model the 3D structures of molecules and complexes containing carbohydrates starting from monosaccharide building blocks, being also

• different monosaccharide building blocks is dictated by the values of different glycosidic torsion angles. MM calculations: Investigating the energetically favourable conformations of carbohydrate disaccharide units composing the molecule of interest represents a pivotal step for generating reliable 3D

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• . Titration of CMC with hydrochloric acid, followed by treatment with a mixture of hexamethylene diisocyanide and formalin led to the formation of compact particles with an average diameter of 40–80 nm (Figure 3A). These particles were the main building blocks for the construction of cage-like structures

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• pyrazoles. The review will primarily focus on two major categories: two-carbon and three-carbon building blocks as key intermediates, while other special cases will be summarized separately. Review (3 + 2)-Cyclocondensation – C3-building blocks as key intermediates The majority of the numerous pyrazole

• syntheses known in the literature are based on the condensation of 1,3-dielectrophiles and their synthesis equivalents as C3-building blocks, along with hydrazines as N2-building blocks [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Conceptually, the en route generation of these C3-building

• compounds 38 are also interesting building blocks in pyrazole synthesis. Through the reaction of 1,5-diaryl-1,3,5-pentanetriones 38 with hydrazines, Knorr synthesis of pyrazoles and Fischer indole synthesis can be combined in a pseudo-three-component fashion to give 5-(indol-3-yl)pyrazoles 39 (Scheme 11

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• : Allostreptomyces; β-alkylpyrrole; conformer; cytotoxic; DFT; 4-formylpyrrole-2-carboxylic acid; Introduction β-Alkylpyrroles are key structural motifs in biomolecules and functional organic materials [1]. For instance, β-alkylpyrroles are the main building blocks for the life-essential tetrapyrrole pigments

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• , the interest in CF3CH=CHCF3 (HFO-1336mzz) [6][7][8][9][10][11][12], CF3CH=CHCl (HCFO-1233zd) [13][14][15][16][17][18], CF3CH=CHF (HFO-1234ze) [12][19][20][21][22][23], and CF3CF=CH2 (HFO-1234yf) [12][20][21][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] as fluorinated building

• blocks has significantly increased in the last years. Recently, the E-isomer of 1,2-difluoroethylene ((E)-HFO-1132) has attracted attention as a new refrigerant due to the low boiling point, moderate flammability, and low toxicity [40][41][42]. Also, in patent literature 1,2-difluoroethylene has been

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• bifunctional building blocks (BBs) can quickly increase the diversity of these molecular libraries [6]. Hence, DEL practitioners constantly seek access to novel building blocks [7]. Amino acids (AAs) are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins

• , while also holding a crucial function in many biological processes [8]. Non-canonical amino acids (NCAs) are widely used in medicinal chemistry [9]. Not surprisingly, they also find broad use as bifunctional building blocks (BBs) for DELs. In an early example, an 800-million-members DEL utilized Fmoc