Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• also applied to o-carboranes fused with five-membered ring systems [39][40]. The positioning of the heteroatom in these exo rings governs bonding, leading to restricted conjugation and, consequently, no aromatic stabilization. Importantly, the magnetic field generated by the 3D cluster influences the

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• (CF2H); fluorine; hydrogen bond donors; hydrogen bond strength; Introduction Hydrogen bonding interactions are ubiquitous non-covalent forces in chemistry and biology [1][2][3][4]. In canonical hydrogen bond (HB) donor–acceptor pairs, the donor typically comprises an electronegative heteroatom, such as

• oxygen, nitrogen, or sulfur, and a positively charged hydrogen atom, which interacts with a lone pair on the acceptor. Apart from these common heteroatom-containing hydrogen bond donors, certain carbon–hydrogen moieties can also act in this way, although in a substantially weaker capacity [5][6][7][8][9

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

• chemistry. Combining electrochemistry with transition-metal catalysis is a promising and rapidly growing methodology for effectively forming challenging C–C and C–heteroatom bonds in complex molecules in a sustainable manner. In this review, we summarize the recent advances in the combination of

• –heteroatom (C–X, where X = N, O, or halogens) bonds in organic synthesis. Copper was one of the first transition metals employed in cross-coupling to form C–C and C–X bonds [1][2]. In 1901, Ullmann reported the first cross-coupling reaction for the formation of biaryl compounds in the presence of

• potential of copper-based electrochemical methodologies while also inspiring future research in this rapidly growing field. Review C–H Functionalization Site- and chemoselective C–H functionalization has emerged as a powerful platform for the formation of new C–C and C–heteroatom bonds, offering an

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

• construction of carbon–carbon bonds [5][6][7][8][9][10]. The hetero-Diels–Alder reaction is therefore an attractive strategy for the synthesis of heterocyclic compounds. It involves the reaction of dienes or dienophiles which possess a heteroatom in their structure. In this reaction, the HOMO of the diene and

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

• , we have collected and described the HVI-mediated halocyclisation reactions reported in the literature for each halide. We have organised the examples firstly by the halide nucleophile, and then secondly by the internal heteroatom nucleophile involved in the cyclisation. The selectivity (chemo-, regio

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

• frameworks (COF), have been extensively studied as photosensitizers of singlet oxygen and photoredox catalysts [87][88][89][90]. However, using metal-free porphyrins as photoredox catalysts for C–C or C–heteroatom bond formation is an area which has recently started to be explored. In 2016, Gryko and co

• macrocycles as photocatalysts in organic synthesis, involving both single electron transfer (SET) and energy transfer (ET) mechanistic approaches [84]. This review does not only focus on the metal-free porphyrin macrocycles, but it also covers the area of different porphyrinoid systems, such as heteroatom

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

• , respectively. Based on the position of the nucleophile, a NRP can be cyclized head-to-tail, via an amino acid side-chain, a nucleophilic heteroatom on the N-terminal fatty acyl chain, or as a multimer of repeating sub-structures (Figure 5b). The ring size, ratio of ʟ- and ᴅ-amino acids, etc. may also be the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• . Photocatalytic oxidation of radical A with [IrIV(ppy)3] regenerates [IrIII(ppy)3] and completes the photoredox catalytic cycle. The Bronsted acid catalyzes the formation of the isochroman oxocarbenium ion B, which is then nucleophilically attacked by TBHP to produce the target peroxide 69. Heteroatom (N, O

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

• nucleophiles to unsaturated compounds with electron-withdrawing groups, is a cornerstone in constructing carbon–carbon and carbon–heteroatom bonds [1]. It is instrumental in synthesizing natural products [2][3][4][5] and pharmaceuticals [6], underlining its significance in organic chemistry. Recent

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

• unsymmetrical forms of these salts serve as effective electrophilic arylating reagents in various organic syntheses. The use of diaryliodoniums in C–C and carbon–heteroatom bond formations, particularly under metal-free conditions, has further enhanced the popularity of these reagents. In this review, we

• ]. They offer several advantages over traditional reagents, including low toxicity, high reactivity, and excellent selectivity [43] under simple reaction conditions. The distinctive reactivity of DIAS enables the smooth arylation of various carbon and heteroatom nucleophiles under gentle conditions, with

• overview of arylation of carbon and heteroatom substrates via diaryliodonium salts in metal-free conditions. This review emphasizes the significance and potential of DIASs in contemporary organic chemistry. Review C-Arylation Over the past decade, there has been a surge of interest in metal-catalyzed C

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

• –heteroatom bonds vicinal to alkenyl or alkynyl groups, which are highly valuable for downstream synthesis. At present, unstabilized nucleophiles [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] are commonly used in Cu-catalyzed allylic substitutions because of the inner-sphere

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• variety of transition-metal-catalyzed reactions and photoredox reactions using arylboronates as aryl sources have been energetically investigated for the construction of carbon–carbon or carbon–heteroatom bonds [12][13][14][15]. The preparation of arylboronates often requires pre-functionalized substrates

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• electron transfer processes etc. [26][27][28]. On the other front, doping with heteroatom(s) to the truxene skeleton drastically modulate its unique physical as well as chemical properties besides the geometrical structure, as well [29]. After successful construction of truxene and its asymmetrical isomer

• , that is the isotruxene scaffold [30] – having differences in clipping of fluorene moieties, chemists began to synthesize the heteroatom-doped truxenes as well as isotruxene molecules, so-called “hetero-truxenes/isotruxenes” [31][32][33]. As can be inspected from the scientific literature, to date a

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• reagents, and are widely used in organic synthesis. On the other hand, the use of isocyanides in reactions with heteroatom radicals is limited. However, the reaction of isocyanides with heteroatom radicals is a promising synthetic tool for the construction of nitrogen-containing organic molecules modified

• with a variety of heteroatoms. In this Perspective, we review the addition and cyclization reactions of heteroatom radicals with isocyanides and discuss the synthetic prospects of the reaction of isocyanides with heteroatom radicals. Keywords: aza-Bergman cyclization; heteroatom-mixed system; imidoyl

• of nitrogen-containing functional molecules. To achieve this goal, it is expected to be effective to develop a new method to react heteroatom radicals with isocyanides to generate imidoyl radicals to which various heteroatom groups are attached and to use them as synthetic reagents. However

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

• . In cases where the α,β-unsaturated carbonyl compounds contain a heteroatom in the β-position, aromatization is triggered by elimination under redox-neutral conditions. Tasch et al. successfully coupled aryl halides with α-bromocinnamaldehyde (51) using a Masuda borylation Suzuki cross-coupling (MBSC

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 because some of them contain more than one heteroatom, this resulted in an unequal distribution of the heteroatoms themselves. Thus, due to the design of the dataset construction, the relative prevalence is approximately 6:4:1:1 for B:N:O:S. COMPAS-2 comprises two datasets – COMPAS-2x and COMPAS

• S atoms appear to be more evenly distributed over the property space, however, certain areas can be identified with slightly higher populations of heteroatom-rich PASs. To explore this further, we divided each property into ten evenly spaced sections and binned all the molecules in each respective

• blocks in each bin is equal to 1. The size of each block represents the likelihood of a heteroatom from this bin being a certain type. As we noted in the Data section, the total numbers of heteroatoms are not equal (the ratios of B:N:O:S atoms are approximately 6:4:1:1). Therefore, each block was

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• conditions are best-suited. We have recently established the use of dibenzoyl peroxide (DBPO) as a very powerful oxidant for oxidative heterofunctionalization reactions using simple nucleophilic inorganic salts as heteroatom transfer reagents [39][41]. This was successfully demonstrated for the non-catalyzed

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• -functionalizations by reacting them with suited C- or heteroatom electrophiles. α-Amino acid-derived azlactones 1 are amongst the most commonly utilized starting materials to access more diverse chiral α,α-disubstituted amino acids (Scheme 1A) [20][21][22]. More specifically, these compounds can be engaged in a

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• been known as indispensable building blocks in modern organic chemistry. Many isocyanide-based carbon–carbon and carbon–heteroatom bond forming reactions have been developed in fascinating ways over the past decades [4][5][6]. The famous multicomponent reactions such as Passerini reaction, Ugi reaction

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• and alkyl radicals, has shown great promise in the synthesis and functionalization of various organic molecules [15][16]. These carbon radicals can be generated in several ways. The first and most straightforward method is the homolytic cleavage of labile C–heteroatom bonds, especially alkyl halides

• , C–C, and C–heteroatom bond formations. The best known technique for the creation of alkyl radicals is the homolytic cleavage of the C–X bond of alkyl halides by toxic tin hydride [17]. Later, various efforts have been made to replace toxic tin hydrides with other reagents [33][34][35][36][37][38][39

• , heteroatom-substituted alkenes, and conjugated alkenes. Using alkyl oxalates obtained from readily available alcohols facilitated the construction of intricate alkyl compounds. However, only tertiary alkyl oxalates were applicable to this methodology. In 2019, Studer et al. [49] reported photoinduced C–O

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• such as heteroatom doping and porous defects for unique properties and functions. For instance, with nitrogen atoms as dopants [1][2][3], a range of applications, such as electrocatalysis [4] and gas storage [5], has been exploited. Although the locations of nitrogen, in addition to the types

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• -311++G** method for the TS geometry obtained using CI-NEB and Gaussian16 is shown by histograms in Figure 2c. These TBR barriers calculated using both methods are also provided in Table 1. It is clear from Figure 2c that the TBR barrier solely depends on the type of heteroatom unit used to extend the

• an undesired byproduct due to thermal dissociation. Consequently, the type-Id switch does not meet the criteria for reversible photoswitching desired for an ideal MOST system. This leads to the inference that the heteroatom used to extend the unsaturated bridge of the BBD molecules plays a crucial

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• difunctionalization of alkynes with various heteroatom and carbon nucleophiles [27][28][29][30][31][32][33][34]. Specifically, intermolecular trans-iodo(III)functionalization of alkynes has been achieved using oxygen nucleophiles such as alcohols [28][32], ethers [33], carboxylic acids [31], phosphate esters [31

• other heteroatom nucleophiles is currently underway. Synthesis of N-vinylazoles. Scope of three-component N-alkenylation of azoles. Competition experiments and plausible reaction pathway. Preparative-scale reaction and product transformations. Reaction conditions: (a) Pd(PPh3)4, 4-MeOC6H4B(OH)2, Cs2CO3

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

• . The difference between the two mechanistic pathways is the nature of activation of the carbonyl group. Protic acids induce the protonation of the carbonyl group of the aldehyde or ketone, enhancing its electrophilic character. Whereas, Lewis acid catalysts bind to the heteroatom of the carbonyl group

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• absorption spectra of PTH1 was observed, suggesting the formation of a charge transfer complex of the type 88 [68] (Scheme 17A). tert-Butyl radical (64), along with additional 2° and 3° alkyl radicals, resulting from these EDA complexes were harnessed in C(sp3)-heteroatom bond forming reactions [69], and in

• the three-component alkylacylation of olefins [108]. Alternatively, NHC catalysts can mediate the generation of radical intermediates from NHPI esters via the stabilization of a photoactive EDA complex. In 2020, Wang and Chen reported a photochemical C(sp3)-heteroatom coupling reaction of NHPI esters