Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• , Michael additions, cycloadditions, domino reactions, cascade annulations, Diels–Alder reactions, and Michael–Stetter reactions, to name a few [31][32][33][34][35]. Notably, previous reports have demonstrated that the utility of chiral N-heterocyclic carbene (NHC) catalysts permits contracting asymmetric C

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• toxicity of sulfolane has been mentioned in some other studies [90][91]. Moreover, as illustrated in the Table 2, only methyl oleate and methyl laurate, in conjunction with sulfolane, were categorized as entirely risk-free based on the four pertinent toxicity parameters. In the context of cycloadditions

• solvents. Furthermore, the evidence suggests that the majority of these solvents is hazardous and their utilization is to be avoided. As demonstrated in Figure 8a, the color of the spheres of the customary proportional solvents employed in [3 + 2] cycloadditions is red or yellow, thereby substantiating the

• reactivity of this double bond can pose significant challenges, particularly in cycloadditions or other organic transformations that necessitate extended cycloaddition processes and elevated temperatures. With a boiling point in excess of 260 °C, methyl laurate has the potential to function as a green

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• total synthesis – 2010 In 2010, Siegel and co-workers reported their total synthesis of complanadine A (Scheme 2). Their synthesis centres on two transition metal-catalyzed alkyne–alkyne–nitrile [2 + 2 + 2] cycloadditions to forge the two pyridine rings encoded by complanadine A [21]. Notably, the C2–C3

• and different approaches were developed. The Siegel synthesis harnesses the power and efficiency of two Co-mediated [2 + 2 + 2] cycloadditions to build the C2–C3’-bipyridyl moiety encoded by complanadine A. The Sarpong synthesis leverages a biomimetic approach to rapidly assemble the tetracyclic core

• ] cycloadditions. The Sarpong total synthesis of complanadine A enabled by a biomimetic strategy and C–H activation. The Tsukano total synthesis of complanadine A enabled by Diels–Alder cycloaddition, Heck cyclization, and directed C–H arylation. The Dai total synthesis of complanadine A using single-atom skeletal

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• and pyrrolidinone electrophiles. Organocatalyzed formal [3 + 2] cycloadditions affording substituted pyrrolidines. Synthesis of a hexacyclic compound via an organocatalyzed enantioselective polyene cyclization. Nickel-catalyzed asymmetric cross-coupling reactions. Chiral cobalt–porphyrin

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• [61], [3 + 2] reductive cycloadditions of enal-alkyne [62], [2 + 2 + 1] cycloaddition of acetylenes [63] and cyclization of 1,6-enyne [64] were efficient approaches towards five-membered rings. Since Faraday synthesized hydrocarbons by employing electric current to an acetate solution [65], the use of

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• proposal is that toussaintine C was isolated as a racemic mixture, and sarglamides A and B are derived from one enantiomer of toussaintine C while sarglamides C–E are derived from the other one. The Diels–Alder cycloadditions are basically proceeded through endo-selectivity. The isopropyl group in α

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• approach. This generates the desired spirooxindole connected to a bicyclic amine, with functionality related to the natural products. It is likely that unactivated dipolarophiles could be successful in related intramolecular cycloadditions [18]. Hence this approach could allow access the spirooxindole and

• , 124.0, 123.7, 108.4, 72.0, 48.4, 46.2, 26.4, 21.5; NMR data as reported (no lit. mp) [30]. Cycloadditions with the aldehyde 4 Aldehyde 4 (500 mg, 1.44 mmol), hydroxylamine hydrochloride (160 mg, 2.30 mmol), and iPr2NEt (0.48 mL, 2.76 mmol) in PhMe (10 mL) were heated to 60 °C. After 2 h, N

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• this end, selected representative examples ranging from fundamental processes such as Diels–Alder or Alder–ene reactions to double-group transfer reactions or 1,3-dipolar cycloadditions involving metal complexes are presented. It is found that while more synchronous processes tend to exhibit greater

• ) of the butadiene + ethylene reaction proceeds with a lower barrier (up to 7 kcal/mol) than the corresponding stepwise pathway leading to a diradical intermediate (Scheme 1a) [19][20]. Similar preferences for concerted pathways over stepwise mechanisms were also found for dipolar cycloadditions and

• the aromaticity of the transition state and the activation barriers of different pericyclic reactions spanning from the parent Diels–Alder reactions to higher-order cycloadditions or even transition-metal-mediated transformations [22][23][24][25][26][27][28][29]. By selecting illustrative examples, in

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• derived from 5-mercapto-1H-tetrazoles was also examined. Keywords: 2,5-dihydro-1,3,4-thiadiazoles; enolizable 5-mercapto-1H-tetrazoles; insertion reactions; thiiranes; thiocarbonyl ylides; X-ray analysis; Introduction Cycloaddition reactions, including 1,3-dipolar cycloadditions, are considered as one

• of the most important types of organic reactions with key importance for the development of methods of modern organic synthesis [1][2][3]. Therefore, conversions of 1,3-dipoles which cover not only cycloadditions but also annulation and insertion reaction attract great attention worldwide [2][3][4

• five-membered heterocycles via [3 + 2]-cycloaddition reactions. Depending on the type of the dipolarophile used in these reactions, the target heterocycles may contain only one sulfur atom (cycloadditions with C=C or C≡C dipolarophiles) or more heteroatoms (cycloadditions with C=S, C=O, C=N, N=N, S=O

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• reactions, are separately debated. In addition, mechanistic insights into the reaction of heteropolycyclic systems, cycloadditions, and aza-Diels–Alder reactions are provided. This is important because multicomponent, one-pot reactions have gained interest as potentially more economic, efficient, and

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• 6 exhibiting enhanced chiroptical performance and protonation-induced CPL amplification [19]. Meanwhile, Audisio’s team developed heterohelicenes via regioselective [3 + 2]-cycloadditions, with compound 7 displaying pH-responsive CPL sign inversion (|glum| = +1.1 × 10−3 at 430 nm, −1.2 × 10−3 at 585

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• 2016 complemented by a few older works that were deemed powerful and relevant for illustrating a given reaction mode. Chapter 1 covers strategies for the oxetane ring formation including substitutions, cycloadditions, ring-size manipulations and carbene insertions. Chapter 2 details chemical

• categorised into 6 synthetic strategies as depicted in Scheme 1: a) C–O bond-forming cyclisations, b) C–C bond-forming cyclisations, c) [2 + 2] cycloadditions between carbonyls and alkenes, d) ring expansions, e) ring contractions and f) O–H insertions. In the following subchapters, these strategies will be

• -, particularly 2-methylideneoxetanes have become valuable intermediates in oxetane chemistry as they readily undergo a variety of chemical transformations, including ring-opening reactions with nucleophiles, epoxidations, cyclopropanations and [3 + 2] cycloadditions with nitrile oxides [51][52]. In addition

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• for all substitutes of 6a, 6h, 6r and 6j, which, are not ideal effective for IMDA cycloadditions compared to the other substitute cycloadditions. The R2 substituent on the imidazopyridine moiety in 6 was found to have a significant electronic impact on the IMDA cycloaddition. When R2 is a halogen (Br

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• have attracted considerable attention due to their promise in the total synthesis of alkaloids [16]. Notably, these valuable compounds can be employed as efficient synthons in enamide–alkyne cycloisomerization, [n + m] cycloadditions, pericyclic reactions, and radical cyclizations. A comprehensive

• (−)-dihydrolycopodine, (−)-lycopodine, (+)-lycoposerramine Q, (+)-fawcettidine, (+)-fawcettimine, and (−)-phlegmariurine have been synthesized in a concise and efficient manner, while employment of the [2 + 3] cycloadditions or a polycyclization enables the elegant total synthesis of Cephalotaxus alkaloids

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• facilitated landmark organic transformations, such as the venerable Paternò–Büchi [6][7][8], Norrish–Yang [9][10][11], and enone–alkene cycloadditions [12][13][14], that proceed via the generation of a singlet or triplet diradical through the activation of an unsaturated bond [2][14]. While these seminal

• isomerization of alkenes [18][19], [2 + 2] cycloadditions [20][21][22][23][24], and dearomative [4 + 2] cycloadditions [25][26][27]. When considering conjugated alkenes, the triplet excited state energy and excited state lifetime are intrinsically linked to the degree of conjugation and substitution of a

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• comes with higher costs, more complex operation, and challenges in effectively integrating light sources for photomechanochemical reactions. Manual grinding Manual grinding was predominantly used in the early days of photomechanochemistry, when [2 + 2] photochemical cycloadditions were extensively

• enhancement of photocatalyzed [2 + 2] cycloadditions under aerobic conditions, even though over longer irradiation times the solution-state yields are superior (Scheme 11D). Very recently, Wu, Wang, and co-workers proposed a radically different approach to photomechanochemistry [78]. Rather than trying to

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -based natural product, which was discovered to induce topoisomerase I-mediated DNA cleavage [16][17]. For the construction of the fluoranthene skeleton, a broad range of synthetic strategies including C–H arylation [18][19][20][21][22], Diels–Alder [7][8][23][24][25] and [2 + 2 + 2] cycloadditions [26

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

• methodologies of 1-azadienes involve a formal [4 + 2] cycloaddition (IEDADA reaction) to construct six-membered nitrogen-containing molecules, α,β-unsaturated imines can also behave as C4 synthons involved in (4 + 1) and (4 + 3) cycloadditions or they act as C2 synthons undergoing (2 + 3) cycloadditions for

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

• potential as functional handles for downstream elaboration of CuAAC products. To date, the main use of germanyl alkynes in (3 + 2) cycloadditions has been limited to a small number of Huisgen (non-Cu-catalysed) reactions [68][69]. Zaitsev and co-workers reported the synthesis and CuAAC reactions of a

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• and 1n were studied. Both gave the expected products in yields of 50% (for 3m) and 44% (for 3n). Besides these successful transformations several ketones proved unsuitable (Scheme S1 in Supporting Information File 1). Additionally, attempted [4 + 1]-type cycloadditions of three 1-arylprop-2-en-1-ones

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

• ethynylethylene carbonates as the starting materials, thus completing their enantioselective formal [4 + 1] cycloadditions with cyclic 1,3-dicarbonyl compounds (Scheme 36, 34a–k). They speculated that in the reaction mechanism, the key step is the formation of the copper vinyl allenylidene intermediate from vinyl

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

• were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern

• with electrophiles, such as deuteration or electrophilic chlorination using N-chlorosuccinimide, in this consecutive three-component synthesis to give persubstituted pyrazoles 165 (Scheme 55) [162]. (3 + 2)-Cycloaddition – C2 building blocks as substrates 1,3-Dipolar cycloadditions are important

• ) cycloadditions with alkenes or alkynes to form pyrazoles, also in the sense of MCR. Furthermore, while not strictly classified as pericyclic reactions, hydrazones are also recognized as CN2 building blocks in pyrazole synthesis [169]. 1,3-Dipoles as key intermediates Various methods have been developed for the

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• decarboxylation of the carboxylic residue when heated at reflux of methanol. After the regioselective cycloadditions, spiro compounds 49a,b were obtained in yields ranging from 75% to 91% (Scheme 15). Related derivatives have similarly been achieved in good to excellent yields [32][33]. Recently, López et al

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• reactant. This isomerization can be reversed by light of a different wavelength or thermal stimuli. Depending on the nature of the reactant, different classes of photoreactions can be utilized: double bond isomerizations, electrocyclization, cycloadditions, and electron-, hydrogen-, or group transfer [1