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

• from the photoexcited Ir complex, Giese-type addition of the resulting triplet diradical 164 to the electron-deficient alkene, intersystem crossing generating a singlet diradical 166 and intramolecular radical recombination. In 2022, Bull and colleagues disclosed an unprecedented synthesis of 3-aryl-3

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• diradicals here – accepting that some of the described molecules would fall under the more specific and accurate terms biradical or diradicaloid. Diradical is the most widely preferred termination in the community, when the general concept and class of molecules with two unpaired electrons is discussed

• quinodal electronic structure, diradicals with broken Kekulé-conjugation exhibit much stronger diradical character. In accordance with the above-described nomenclature, these diradicals are termed non-Kekulé diradicals. This tendency of diradicals to form a closed-shell electronic configuration can be

• described using the diradical index y0, which corresponds to a closed-shell system for y0 = 0 and a purely open-shell diradical for y0 = 1. In the open-shell electron configuration, the diradicals can acquire a singlet state with open-shell but antiparallel spins (total electronic spin, S = 0) or a triplet

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

• ). Pioneering studies have leveraged this platform with great effect, typically invoking π→π* transitions of conjugated alkenes to lower the bond order and generate a triplet diradical, primed for further reactivity. This key intermediate is pivotal in a plenum of synthetic transformations including geometric

• demonstrated the efficient sensitization of an alkene-containing four boron substituents using Ir(ppy)3 as a suitable sensitizer in the presence of styrene, indicating a prominent role of the adjacent p-orbital [51]. While simple alkenylboronic esters have been employed as triplet diradical quenchers to

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• diradical. This triplet diradical undergoes another ISC, returning to the singlet state, which then forms a second single bond (Figure 8). This mechanism, involving both singlet-excited states and triplet states via ISC, is consistent with the relatively low fluorescence quantum yields observed for Cl2B

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• pentacenes, are relatively stable molecules under ambient conditions, longer acenes undergo spontaneous dimerization and react with oxygen [5][6], owing to the rising diradical character. This behavior was also observed in the oxidized species of shorter acenes [7]. Surprisingly, Bettinger and Einholz [5

• the entire molecule of m-12+. It also justifies the behavior of the Raman bands and the changes in the CC bond force constants. In further agreement with this description, we found that m-12+ discloses a singlet closed-shell ground electronic state without any trace of diradical character. Thus, the

• the fact that the ground electronic state of m-22+ converges into an open-shell diradical structure (more stable than the closed-shell one by 1 kcal/mol at the DFT/(U)B3LYP/6-311G(d,p) level). Both 1 and 2 are composed of a total of 30 π electrons, which correspond to the Hückel count of 4n + 2, with

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• . Access to the dianion of BFC presages an interesting diradical and this was achieved by inclusion of mesityl protecting groups [27]. Extension of the BFC model with thiophene provides further interesting materials [28]. A reasonable corollary to this behavior would assert that derivatives of TBF and

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

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• population analysis revealed that 0.26 e of electron density was transferred to iodine, resulting in a 1,2-diradical (41*, Figure 9). In their mechanistic proposal, they presumed that this excited species would not have been sufficiently long-lived to encounter the styrene (41*→43*). Instead, they invoked an

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• , catalyzed by a copper catalyst [39]. Murphy and co-workers reported blue LED-mediated metal-free cyclopropanation of alkenes with iodonium ylides through a diradical intermediate [40]. However, iodonium ylides are relatively unexplored for the arylation of amines. So far only Spyroudis’s group reported N

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• the triplet-state diradical 23-I. A HAT process between 23-I and the alkane substrate generates the desired carbon-centered radical 23-II with concomitant formation of ketyl radical species 23-III. The thus formed alkyl radical 23-II undergoes Giese addition to alkene 94 resulting in the radical

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• the activation energies for both cis–trans-isomerization and for the transformation of vinylcyclopropanes into cyclopentenes. Both processes could occur by a C–C-bond homolysis to form a diradical. Computational studies by Gety, Hrovat, and Borden indicated that there would be a preference for

• opposite to the CF2 moiety, which was followed by the recyclization of the intermediate diradical (Scheme 42). The activation energy for the rearrangement of 90 was lower by 9.4 kcal/mol than for the parent hydrocarbon system 92. The activation energy of the trans-isomer 91 was greater than that of cis

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• energy charge transfer state that can be photoexcited to generate singlet intermediate 89*. Subsequent enantioselective photocycloaddition with 88 via diradical 90 gives iminium ion intermediate 91, which after hydrolysis affords the desired cyclobutane products 92 in excellent yields and good

• to generate diradical 177 that then adds to the alkene to form diradical 178. A SET between the ketyl radical and the α-carbonyl radical generates enolate intermediate 179, which after proton transfer regenerates the catalyst and releases the desired cyclisation product 180 in a moderate yield and

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• cycloadducts 28 were identified in the mixture, the reaction with Z-1b afforded four diastereoisomers of type 28 (Scheme 8). The observed stereochemical outcome was explained by a diradical mechanism with isomerization of the intermediate 29 taking place only in the reaction with Z-1b. As side products

• changes to non-concerted stepwise processes, which can involve zwitterionic or diradical intermediates. [4 + 2]-Cycloadditions (Diels–Alder reactions) In analogy to reactions with tetracyanoethene (TCNE), the first [4 + 2]-cycloadditions (Diels–Alder reactions) of E-1a were performed using typical 1,3

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• -methanide 3 and the sterically crowded 4,4,5,5-tetraaryl-1,3-dithiolane 5 were obtained (Scheme 1) [20]. The formation of both products was rationalized by the assumption that the in situ formed 3a reacts as a delocalized diradical species. In a recent publication, similar reactions of TMS-CHN2 with 1a and

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• between 2 and 3, the truncated structures 2a and 3a (Figure 1) were used. Geometries of 2a and 3a in MeOH solution in S0, S1, and T1 states were optimized by DFT (for S0 and T1) or TDDFT (for S1 only) calculations at the B3LYP/def2-SVP level. For diradical triplets, the spin-unrestricted formalism was

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland 10.3762/bjoc.13.44 Abstract An intriguing stepwise diradical mechanism of the dimerization of the reactive intermediate (thiocarbonyl S-methanide) appearing in the reaction of phenyl selenophen-2-yl thioketone with diazomethane was studied by means of

• intermediate, delocalized diradical species. The influence of selenium as a ‘heavy atom’ for stabilization of this intermediate has been emphasized. Keywords: 1,3-dipolar cycloadditions; reaction mechanisms; reactive intermediates; thiocarbonyl S-methanides; thioketones; Introduction Thiocarbonyl S

• processes have not been studied in detail yet. Whereas the formation of the 1,3-dithiolane 4 can be explained via a concerted [2 + 3] cycloaddition of 1 as a 1,3-dipole with the activated C=S bond of 1, the dimerization leading to 5 seems to occur stepwise via an intermediate stabilized 1,6-diradical 6. In

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• 1,5-diradical as a key intermediate. The complete change of the reaction mechanism toward the concerted [3 + 2]-cycloaddition was observed in the reaction of a sterically crowded cycloaliphatic thiocarbonyl ylide with ferrocenyl methyl thioketone. Keywords: [3 + 2]-cycloadditions; 1,3-dithiolanes

• -tetrasubstituted 1,3-dithiolanes [6][7], cycloaliphatic S-methanides tend to form mixtures of both regioisomeric cycloadducts with the major component being the sterically more crowded isomer [7][8]. In a recent study, we proposed a diradical mechanism for the [3 + 2]-cycloadditions of thiocarbonyl S-methanides

• thiocarbonyl S-methanides with aryl and hetaryl thioketones, we propose that the reactions with ferrocenyl thioketones 1 occur predominantly via an intermediate 1,5-diradical. The formation of the sterically more crowded 1,3-dithiolanes 5a–g confirms that the stabilized 1,5-diradicals of type 7 (Scheme 4) are

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• (trimethylsilyl)diazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates

• assumption that they occur via diradical intermediates [13][14][15]. Reactions of aromatic thioketones with diazomethane are well established. For example, in the case of thiobenzophenone (1a), the reaction performed at –65 ºC occurs without evolution of N2 and the in situ formed 2,2-diphenyl-1,3,4

• , leading to unusual dimers 5 of intermediate thiocarbonyl ylides of type 3c [22] (Scheme 2). In a competitive reaction, the latter react with the starting thioketone 1c to give 1,3-dithiolanes of type 6 which are, apparently, also formed via a diradical pathway, leading to the sterically crowded 4,4,5,5

Solving the puzzling competition of the thermal C²–C⁶ vs Myers–Saito cyclization of enyne-carbodiimides

• Anup Rana,
• Mehmet Emin Cinar,
• Debabrata Samanta and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 43–49, doi:10.3762/bjoc.12.6

• by applying the DFT method. The results indicate that enyne-carbodiimides preferentially follow the C2–C6 (Schmittel) cyclization pathway in a concerted fashion although the Myers–Saito diradical formation is kinetically preferred. The experimentally verified preference of the C2–C6 over the Myers

• –Saito pathway is guided by the inability of the Myers–Saito diradical to kinetically compete in the rate-determining trapping reactions, either inter- or intramolecular, with the concerted C2–C6 cyclization. As demonstrated with enyne-carbodiimide 11, the Myers–Saito channel can be made the preferred

• pathway if the trapping reaction by hydrogen transfer is no more rate determining. Keywords: DFT computation; diradical; enyne-carbodiimides; hydrogen transfer; thermal cyclization; Introduction The thermal cyclizations of enediynes [1][2][3][4][5][6], enediallenes [7][8][9][10], bisallenes [11], enyne

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• formation of 52 must be explained by a different mechanism. One alternative could be the photochemical generation of a diradical from the conjugated oligoene 19 and interception of the former by the oxygen present in the reaction solution. Interestingly, when the solution is degassed before irradiation and

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• isomerization to the desired cis-isomer 9 at elevated temperature (≈200 °C [1][2], lowered for more conjugated systems). The isomerization pathways have been suggested to proceed either via the formation of intermediate diradical-species (pathway A, Scheme 3) [16][20][26][27] or through one-center epimerization

• (pathway B) [28][29]. Following pathway A, the C1–C2 bond of 15 is cleaved homolytically to give diradical 16. The two radicals are stabilized as allylic radicals (depicted as 16'), rotation around the C1–C3 bond takes place (16' to 16'') followed by radical recombination to give cis-divinylcyclopropane (9

• ). Pathway B proceeds through the formation of planar allylic anion 17, which undergoes inversion to give cis-divinylcyclopropane (9). An alternative reaction pathway of the trans-divinylcyclopropane (15) to yield the cycloheptadiene product is the direct formation of the seven membered ring from diradical

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• diradical 9 [27]. The latter can then either undergo ring closure to form indan-2-one (IN), or decarbonylate to give o-xylylene (XY). The equilibrium of XY and benzocyclobutene (BC) is established in the literature [28], as well as the formation of styrene ST from BC [29]. An alternative mechanism, the

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• formation process) were determined by the temperature-dependent change of the lifetime. The energy barrier was found to be largely dependent upon the substituents Ar and Ar’. The singlet diradical DRf (Ar = 3,5-dimethoxyphenyl, OCH2Ar’ = OCH2(3,5-dimethoxyphenyl)) was the longest-lived, τ293 = 5394 ± 59 ns

• , among the diradicals studied here. The lifetime of the parent diradical DR (Ar = Ph, OCH2Ar’ = OCH3) was 299 ± 2 ns at 293 K. Conclusion: The lifetimes of the singlet 1,3-diyls are found to be largely dependent on the substituent pattern of Ar and Ar’ at the C(1)–C(3) positions. Both the enthalpy and

• -diyls [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and cyclopentane-1,3-diyls [17][21][22][23][24][25][26]. Detailed experimental study of singlet diradical chemistry is thus now possible using the long-lived localized singlet diradicals. So far, we have studied singlet diradical