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

• to the AAA coupling, except for iron, where the temperature must be increased to 100 °C. This can be explained in terms of the activation of both the C–H and C–X bonds by metal catalysis, which is not the case in AAA couplings, where only the C–H bond is activated, making the last step (nucleophilic

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• [Os(tpy)2]2+/red-light irradiation system well-suited for large-scale manufacturing. In this way, the authors have also tested different osmium complexes in various well-established photocatalyzed reactions such as copper, palladium, cobalt, and nickel metallophotoredox couplings using red light

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

• systems combining copper catalysis with electrocatalysis have been developed to avoid the use of chemical oxidants. Thus, the substrate scope was expanded to include electron-deficient arylboronic acids. In 2019, Gale-Day et al. developed electrocatalytic Chan–Lam couplings of arylboronic acids with

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• of stereoselective Suzuki–Miyaura couplings, offering precise control over both categorical and continuous variables (Figure 2a) [15]. The integrated robotic system containing a four-needle dispense head facilitated the delivery of reagents in low volume and slurries, ensuring the accuracy and

• Buchwald–Hartwig aminations [16][17][18][19], Suzuki couplings [16][17][20], N-alkylations [21], hydroxylations [22], and photochemical reactions [23][24][25][26][27][28][29]. The versatility to handle multiple reagents and the widespread availability of 96-well plates have facilitated the extensive

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• cross-couplings. Schoenebeck and co-workers have shown that Ge-based compounds are versatile reagents within chemoselective cross-coupling processes for the formation of a variety of C–C and C–X bonds [55][56][57][58][59][60][61][62][63]. Importantly, these transformations can take place in the presence

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

• the radical Kharasch-type functionalization of organic molecules with OOR fragment including free-component radical couplings. The discussion has been structured by the type of the substrate of radical peroxidation: C(sp3)–H substrates; aromatic systems; compounds with unsaturated C–C or C–Het bonds

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

• -arylations utilizing diaryliodonium salts, marked by significant contributions, notably from research teams led by Sanford [53] and Gaunt [54]. The synthesis of carbon–carbon bonds through metal-free approaches serves as a valuable complement to transition-metal-catalyzed couplings. This is particularly

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• organometallic Mannich couplings involving nonstabilized organometallics are uncommon and mostly limited to dialkylzinc reagents, likely due to their commercial availability, their significant reactivity, and their functional-group tolerance [7][8][9][10]. However, the molecular diversity accessible with these

• species 2 were collected using a syringe and allowed to react with an amine 3 and an aldehyde 4 under moderate heating (Scheme 2). The multicomponent couplings proceeded smoothly, with an acceptable yield of the α-branched amine being obtained after 3 h at 50 °C. A range of secondary amines as well as

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

• coupling reactions, Suzuki–Miyaura couplings are known to be a robust tool when functionalizing porphyrins [29][30]. Many complex porphyrinoid architectures have been synthesized in this manner, from functional porphyrin arrays [31][32][33] to sterically challenging meso-substituted aryl bis-pocket

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

• Suzuki couplings and the reduction of the thiazole moiety to 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a crucial intermediate, using BH3⋅NH3 and tris(pentafluorophenyl)borane as a Lewis acid, followed by treatment with formic acid. Gillie et al. reported the synthesis of a laterally fused N-heterocyclic

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

• chlorine atoms as reported by Hosoya and Niwa et al. In this study, we investigated the synthesis of fluoroalkenes 2 or fluoroenynes 3 by Suzuki–Miyaura or Sonogashira cross-couplings with a key building block 1 (Scheme 1D). Results and Discussion Optimization of the conditions of cross-coupling reactions

• cross-coupling between 1e, derived from m-aminophenol, and 4a proceeded in only 15% yield (Table 3, entries 17 and 18). We performed Sonogashira cross-couplings between 1 and a variety of alkynes 5 (Table 4). Arylacetylenes, which have electron-donating substituents on the aromatic ring (5b–f), and 2

• fluoroalkenes could be synthesized by applying other cross-couplings to 2. In addition, enynes 3 could be converted into derivatives, such as fluorine-containing alkynylalcohols [47], allene compounds [48][49][50], and heterocycles [51][52]. However, further experiments are required to expand the abilities of 2

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

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• Kohn–Sham orbitals produced from DFT are localized to describe the system as one dominant resonance structure. As the Fock matrix is not diagonal in terms of the NBOs, coupling between orbitals can be quantified with second order perturbation theory. These couplings represent donation from an occupied

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

• catalysts’. While the concept of generality was recently explored in a closed-loop fashion for Suzuki–Miyaura cross couplings to find the most general catalyst and reaction conditions [131], the application of this concept in the context of ML has found comparatively less attention in organocatalysis

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

• predicted protein interfaces into the docking process through ambiguous interaction restraints and allows the specification of precise distance restraints (e.g., based on MS cross-links). It also supports a range of experimental data, including NMR residual dipolar couplings, pseudo contact shifts, and cryo

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

• = Cl, Br). The resulting 4-halopyrazoles 111 can either be isolated or undergo further Suzuki coupling with arylboronic acids. Both couplings use the Pd catalyst in a sequential fashion. To increase the yields, both cyclization and Suzuki coupling are carried out with microwave support. Some of the

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

• the blue region. This complex then accelerates the oxidative addition of the aryl halide to the metal, which is usually the rate-limiting step for palladium-catalyzed cross-couplings. Based on these results we decided to perform all Negishi reactions under blue light irradiation. With the optimized

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• previous mechanistic study [20][21] which revealed that the intermolecular C–N and C–C couplings are disfavored in case of the diarylamines with two electron-deficient phenyl rings. To our surprise, the procedure did not work in the case of amine A3: only traces of pyridoindazolium salt S3 were detected in

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• -substrate interaction. Phenotellurazine-catalyzed cross-dehydrogenative couplings. Screening of new Te(II)-catalyst candidates. ODCB: ortho-dichlorobenzene. Phenotellurazine-catalyzed cross-dehydrogenative indole dimerization. Supporting Information Supporting Information File 84: Experimental section and

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

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

• performed in 68% and 74% yields, respectively (Scheme 4a). Furthermore, the iodanyl group on these products serves as a versatile handle for downstream transformations, thus allowing for the stereoselective preparation of various trisubstituted N-vinylazoles (Scheme 4b). Pd-catalyzed C–C couplings such as

• Suzuki–Miyaura and Sonogashira couplings on 4aa or 4ba afforded the desired products 5 and 6 in 47% and 74% yields, respectively. In the former case, the C–Br bond on the pyrazole moiety remained intact, highlighting the superior leaving group ability of the BX group. Cu-catalyzed Ullmann coupling

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

• reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations. Keywords: decarboxylative couplings; mechanisms; NHPI-esters; radical reactions; Introduction The historical challenges of using radicals in synthetic

• phthalimidyl anion would generate the aminoalkylation product 119, completing the catalytic cycle. In addition to this aminoalkylation method, the synthetic utility of radical intermediates derived from NHPI esters under photoinduced Pd-catalysis has been demonstrated in Heck-type couplings [81][82] and in the

• decarboxylative cross-coupling (DCC) of NHPI esters with organometallic reagents, resembling classic Kumada, Negishi, and Suzuki couplings, has been enabled by nickel (Ni), cobalt (Co), iron (Fe), and copper (Cu) catalysts [84][85][86][87][88][89][90][91] (Scheme 23A). The typical mechanism begins by

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

• structure, 3H-phenoxazin-3-ones can easily be accessed through oxidative couplings of o-aminophenols [3][4] or N-aryl-o-benzoquinone imines [5][6]. Further, they can serve as efficient precursors of pentacyclic N,O-heterocyclic compounds that possess promising properties for application in fluorescent

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

• performing the reaction of o-phenylenediamine (1a) with 2-bromophenylboronic acid (7) in the presence of Cu(OAc)2, Et3N as base in DCM at 50 °C (entry 1, Table 4), and gratifingly under these conditions, the reaction afforded compound 3a in 48% yield. The Chan–Lam couplings were undertaken under an aerobic

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• variety of reactions; that are, phosphite- or Lawesson’s reagent-mediated olefination reactions (to introduce DTF motifs), Ramirez/Corey–Fuchs dibromo-olefinations followed by Sonogashira couplings (to introduce enediynes motifs), and Knoevenagel condensations (to introduce the vinylic diester motif). By

• various elaborate systems [24][25][26][27]. Next, we wanted to explore IF-DTFs as motifs for acetylenic scaffolding (Scheme 4). Starting from IF-DTF building block 6, dibromo-olefinated compound 18 was obtained by a Ramirez/Corey–Fuchs reaction. Two-fold Sonogashira couplings with trimethylsilylacetylene

• Sonogashira couplings of compound 25 with triisopropylsilylacetylene and ((2-ethynylphenyl)ethynyl)triisopropylsilane yielded compounds 26 and 27, respectively. A two-fold, intramolecular Glaser–Hay coupling of compound 27 (after desilylation) was attempted under the conditions that were successful in the