Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• generate crotonic condensation adducts of active methylene compounds and formaldehyde at room temperature in the absence of strong acids and bases. The formed adducts were highly reactive intermediates capable of reacting with dienes in a three-component reaction, leading to the formation of Diels–Alder

• various CH acid derivatives and conjugated dienes (cyclopentadiene, 1,3-cyclohexadiene, 2,3-dimethylbutadiene and isoprene), leading to [4 + 2]-cycloaddition adducts (Scheme 1). It should be noted that in previous works describing three-component reactions of carbonyl compounds, conjugated dienes and

• , were found. The preferential formation of diastereomers 4a and 5b during the Diels–Alder reaction with the corresponding methylidene adducts was consistent with literature data [24][26]. Next, we studied three-component condensation reactions in the presence of the less active dienes cyclohexadiene

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• phosphite were ineffective (Table 1, entry 5), the inclusion of chelating dienes improved the yield of 3bb (Table 1, entries 6–8). Among these, 5 mol % of 1,5-cyclooctadiene (cod) proved to be the most effective additive, affording 3bb in 95% yield (Table 1, entry 8). Additionally, by reducing the

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

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

• the LUMO of the dienophile interact to construct the six-membered heterocyclic derivative and the reaction requires electron-rich dienes and electron-poor dienophiles (Figure 2a). In the inverse electron demand hetero-Diels–Alder reaction (IEDHDA), the LUMO of the diene interacts with the HOMO of the

• dienophile, and therefore it proceeds through the reaction of electron-poor dienes and electron-rich dienophiles (Figure 2b). α,β-Unsaturated imines can undergo inverse electron demand aza-Diels–Alder reactions (IEDADA) to produce N-heterocyclic compounds. The search for an enantioselective pathway to carry

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

• ]-cycloaddition reaction between electron-poor 1,2-diaza-1,3-dienes and electron-poor alkenes in refluxing acetonitrile was reported leading to various substituted tetrahydropyridazines in 17–78% yields (Scheme 1c) [26][27]. Nevertheless, these methods are neither relevant for the synthesis of 1 nor appropriate

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

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

• -3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition

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

• Abstract A new class of heterocyclic N,O-aminal and hemiaminal scaffolds was successfully obtained by means of a three-component reaction (3-CR) of 1,2-diaza-1,3-dienes (DDs), α-aminoacetals and iso(thio)cyanates. These stable imine surrogates are generated from key-substituted (thio)hydantoin

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• product. The reaction proved to be rather general and various dienes and chromones were successfully employed to give the corresponding benzozocoumarines in good yields. The yields were in most of the cases in the range of 42 to 65% (over two steps) and did not depend much on the substituents attached to

• type of product is formed in the reaction of 3-formylchromones with (2,4-dioxobutylidene)phosphoranes [37]. The yields were in a range of 33 to 82%. No clear trend was observed for the yields depending on the structure of the diene and the chromone. Similar to unsubstituted diene 6a, dienes containing

• a substituent R5 located at carbon C-4 gave good yields, except for methoxy and benzyloxy which did not work at all. Dienes derived from 1,3-diketones (R6 = Me, Ph) gave similar yields to those obtained from dienes derived form β-ketoesters, although yields were slightly lower in case of R6 = Me

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

• Figure 1a, the previously studied BBD-based photoswitches (NBD/QC and BOD/TCO) generate photoisomers with two strained 3-membered rings. In contrast, the photoinduced chemical transformation of all studied bicyclic dienes yield photoproducts containing one 4-membered and one 3-membered ring. Therefore

• role in determining the stability of the metastable photoproduct against undesired thermal degradation. Photophysical properties Photoabsorption of bicyclic dienes in the visible region of the solar spectrum is one of the prerequisites for their applicability as photoswitches in MOST systems. Therefore

• , forecasting the photophysical properties of BBD switches is one of the prominent objectives of the present investigation. The optical spectra of the dienes and photoproducts of both the types of BBD switches are depicted in Figure 4. The optical spectra were obtained as the outcome of the first fifteen

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• equivalent. Synthesis of 1,4-BCHs 100a–f via intramolecular [2 + 2] cycloaddition of hexa-1,5-dienes was reported by Rigotti and Bach (Scheme 11A) [55]. These reactions require the presence of one styrenyl motif for efficient excitation. Derivatization of some of the compounds formed led to further useful

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• be difficult to achieve using either radical or polar chemistry alone. In recent years, Gevorgyan, Glorius, Huang and their co-workers reported elegant examples of the carboamination of 1,3-dienes with unactivated alkyl halides and amines under photoinduced palladium catalysis via a radical-polar

• process (Scheme 1c). In this process, the hybrid α-ester alkylpalladium radical species from diazo ester adds to the double bond of 1,3-dienes or allenes, followed by the allylpalladium radical-polar crossover path. As with the classical Tsuji–Trost reaction, a subsequent nucleophilic attack of an amine

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

• reported in recent years, including decarboxylative alkynylations [76][77][78] and the C(sp3)–H alkylation of α-amino acids [79]. The ability of NHPI esters to act as dual reagents was also investigated by Glorius and co-workers in the context of a photoinduced Pd-catalyzed aminoalkylation of 1,4-dienes

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• to generate the trisulfide-2-oxide moiety. Thermal activation of 47 in refluxing chlorobenzene triggered the elimination of SO, which was subsequently trapped by a variety of conjugated dienes such as 2,3-dimethylbutadiene (48), to afford in good to excellent yields 2,5-dihydrothiophene S-oxides

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• developed by means of [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes. This approach displays advantages such as mild reaction conditions, wide substrate range tolerance, simple operation, compatibility with gram-scale preparation. Keywords: [4 + 2

• ] annulation reaction; 1,2-diaza-1,3-dienes; spiro-benzosultams; 3-substituted benzoisothiazole 1,1-dioxides; Introduction Spirobenzosultams have various biological activities [1][2][3] such as antiviral, anticancer, antimicrobial, antimalarial, and antileukemia, and are widely used in the pharmaceutical

• ketimines as suitable three-carbon synthons in [3 + 2] and [3 + 3] annulations [11][12][13][14][15]. However, methods using N-sulfonyl ketimines as dienophiles in [4 + 2] annulation reactions to afford biologically important spiro compounds are still limited to date [16]. 1,2-Diaza-1,3-dienes [17][18][19

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• flash vacuum pyrolysis to 1,5-hexadiyne. When 3,4-bis(methylene)cyclobutene undergoes a reaction with dienes like 1,3-diphenylisobenzofuran and 1,3-diphenylisonaphthofuran, it selectively produces compounds 22a and 22b. In the subsequent step, the exocyclic methylidene groups react with bisarynes, which

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• advantages are (i) the universality to a wide range of monomers such as (meth)acrylates, (meth)acrylamides, dienes, vinyl ethers/esters, etc.; (ii) tolerance to unprotected functionalities in monomers and the solvent including –OH, –COOH, –SO3H, etc.; (iii) different reaction conditions, including bulk

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• are available [2][3], only a couple of cycloaddition reactions has been reported [4]. For example, [3 + 2] dipolar cycloadditions to form saturated difluoroisoxazolidines [5][6] and difluoropyrrolidines [7] and [4 + 2] cycloaddition reactions with gem-difluoro-1,3-dienes [8]. The overall landscape of

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

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

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement. Keywords: 1,4-dihydropyridine; electron-withdrawing alkyne; formal [2 + 2] cycloaddition; Huisgen's 1,4-dipole; isoquinoline

• [4.2.0]octa-3,7-dienes 5a–o could be successfully obtained in moderate to good yields by carrying out the reaction of dimethyl acetylenedicarboxylate and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile for three hours (Table 3). As can be seen, unsymmetric 1,4-dihydropyridines with N–Bn

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• a wide substrate scope of both pyridines and olefins including α-olefins, styrenes, and conjugated dienes. The yttrium complex was found to be superior as compared to the scandium complex for the alkylation reaction of bulkier 2-tert-butylpyridine with ethylene. In addition, the yttrium catalyst was

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• ) [66]. Variations of this reaction include alkyne metathesis [67] and carbonyl metathesis [68]. Ring-closing metathesis (RCM) gave access to a series of dibenzo[b,f]heteropines, as reported by Matsuda and Sato [31] (Scheme 25). The authors synthesised a series of Si-, Sn-, Ge- and B-tethered dienes 118

• from 2-bromostyrene (116) via halogen–lithium exchange and quenching with the appropriate heteroatom source (SiR2Cl2, SnMe2Cl2, GeR2Cl2, BBr3). P-Tethered dienes were synthesised via quenching of a 2-vinylphenyl Grignard reagent with phenylphosphonic dichloride (PhPOCl2). O-Tethered dienes were

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• , including cross-coupling-type chemistries on a conformationally stable cis-vinyl zinc building block. 3 Diels–Alder reactivity of 1,4-dithiin-based dienophiles and dienes Vinyl sulfones and vinyl sulfoxides are classical synthetic equivalents of ethylene in Diels–Alder reactions, and have been widely used

• analog 26 should also be a reactive dienophile [51], but is a less useful building block, as it reacts twice and the adducts will not be as easily desulfonylated. The dienophile 7 reacts with a wide range of dienes at room temperature, without the need for a Lewis acid catalyst. This is particularly

• helpful when dealing with sensitive dienes. A nice illustration of this is afforded by De Lucchi’s simple synthesis of barrelene (33) from oxepin (29, Scheme 8b) [52]. Oxepin’s equally unstable valence tautomer 30 (benzene oxide) is quite reactive as a diene in Diels–Alder reactions, and can react with 7