Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• , culminating in cyclization mediated by N,N'-dicyclohexylcarbodiimide (DCC)/N-methylmorpholine (NMM) at 0 °C for 7 days [18]. This method, however, is lengthy, operationally complex, difficult for product isolation, and carries a significant risk of racemization. Wong and Jolliffe synthesized segetalins B (2

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• intermediate Int 16 on VQM to form intermediate Int 17. As bifunctional organic catalysts, chiral ureas can synergistically activate both alkynes and selenols, thereby addressing the challenge of overcoming the increased difficulty of racemization caused by the presence of bulky SeR groups (Scheme 5). Summary

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• that in the field of chiral drug R & D, the evaluation of bio-profiles of both enantiomers and racemic compound is required by the U.S. FDA. The result presented herein shows that by a late-stage racemization, one could obtain a racemic sample in just one step, instead of repeating the total synthesis

• from another enantiomeric chiral starting material or racemic one. On the basis of this consideration, such racemization represents a valuable “enantiodivergent synthesis”. Nevertheless, a more useful and generally acceptable enantiodivergent synthesis is the one that allows accessing two enantiomers

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• conducted a thorough evaluation of the stability of the helical chirality across the synthesized quinohelicenes, indicating a high racemization barrier. In 2024, our group further extended the CPA-catalyzed sequential Povarov reaction and aromatization strategy by using 2-vinylphenols 14 as the olefin

• -membered cyclic ketones 74 and hydroxylamines 75 (Scheme 21) [57]. High to excellent yield and enantioselectivity were achieved for the inherently chiral products when using a range of substituted arylhydroxylamines (see 76a–c). The racemization barrier of the product 76a was determined to be 110.5 kJ/mol

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• -preparative chiral IH column. The rotational barriers of 1a and 1b were evaluated to be 32.0 and 30.8 kcal mol−1, respectively, by a thermal racemization experiment of the separated (P)-1a and (P)-1b. In contrast to quinolinones 1a,b, the atropisomers in the precursors (3,4-dihydroquinolinones 4a,b) could not

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• peaks corresponding to the atropisomers arising from the C–C axis. Each atropisomer could be separated by chiral HPLC, and the isomer eluting earlier was used for the following kinetic analysis. The effect of pH on the kinetics of the racemization was investigated. The isomer was heated in the buffer

• . Notably, at pH 9.2, racemization proceeded minimally, even under high temperature conditions. Furthermore, it was confirmed that racemization requires a higher pH where a higher proportion of the amidine exists in its molecular form. This result was consistent with our DFT calculations, which showed that

• the rotational barrier of the C–N/C–C concerted rotation is higher than that of C–N rotation. This finding is consistent with the calculated pKa of 10.6 for amidine 1, indicating that racemization is minimal under the conditions where most of the amidine remains in its protonated form. As pH was

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• low racemization barrier as with structurally similar methylenedioxy-substituted DBC derivative [22]. Racemization dynamics The racemization barriers of CBBC 1, mono-olefin 3, and bis-olefin 5 were evaluated by monitoring the decrease of circular dichroism (CD) signals in 1,2-dichlorobenzene at 170 °C

• (Supporting Information File 1, Figures S22–S24). The decrease of CD intensity was fitted by a single exponential curve, affording half-lifes of 1.3 h for 1, 6.4 h for 3, and 29 h for 5. These results indicate that the transformation of carbonyl groups to exocyclic olefins is effective to retard racemization

• . The racemization dynamics of 5 was investigated by DFT calculations at the B3LYP/6-31G(d) level of theory, employing the Gaussian 16 software package and the global reaction route mapping (GRRM17) [23] program (Figure 4). The interconversion between figure-eight conformation (M,M)-B and bathtub

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

• reported azabora[6]helicenes 45a and 45b [60]. However, their enantiomers could not be isolated due to low racemization barriers. The F- and Ph-coordinated derivatives displayed moderate PLQYs in solution (0.26 and 0.18, respectively), which dropped markedly in the solid state (0.02 and 0.04) owing to

• reported a bis(N,Se)-hetero[4]helicene 59b and systematically compared its structural and dynamic properties with those of its sulfur analogue 59a [74]. Despite their close structural resemblance, the longer C–Se bond in 59b led to a markedly higher racemization barrier (145.7 vs 112.8 kJ/mol), thereby

• construct aza-oxa-dehydro[7]helicenes, yielding helicenes with high racemization barriers and notable chiral stability [84]. The quasicirculenes 70a and 70b demonstrated strong blue CPL activity, with |glum| values of 2.5 × 10−3 at 433 nm and 2.4 × 10−3 at 418 nm, respectively (Table 24). Building on this

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• , compound 7 has a primary alkyl group (n-propyl). This difference reduces steric hindrance and lowers the rotational barrier around the carbon–nitrogen bond, increasing the likelihood of racemization. Results and Discussion N-Propyl-N-cinnamoylamide 7 was prepared from phosphine oxide 8 [32] via an SNAr

• detector and found that the C(aryl)–N(amide) bond axial chirality exists in amide compound 7. We attempted the optical resolution of racemic compound (±)-7 and obtained (+)-7 and (−)-7 using a semi-preparative chiral HPLC on 50 milligram scales. We also investigated the racemization process associated with

• the axial chirality of compound 7 (see Supporting Information File 1). The racemization barrier (ΔG‡rac) of (−)-7 in n-dodecane was determined to be 25.0 kcal/mol at 25 °C, as calculated using the Arrhenius and Eyring equations [33][34][35]. Therefore, the half-life of racemization of ligand (−)-7 at

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

• mixture of right- and left-handed propellers can be resolved by chiral high pressure liquid chromatography (HPLC) into the P- and M-enantiomers, respectively [40][41]. However, due to the low racemization barrier of only about 22 kcal mol−1, the enantiomers racemize within minutes at room temperature. TTM

• is synthesized with slightly improved ϕ of 2% and a blue-shifted emission compared to PTM with a maximum photoluminescence wavelength λem = 569 nm (in CCl4) [40][42]. The racemization barrier remains almost identical at 21.1 kcal mol−1. Both PTM and TTM exhibit circularly polarized emission (CPL) for

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• moiety are non-linear with a Ca–N–C angle of 100°. Due to the stereospecificity of the reaction, racemization would have to occur already in 9 through a topomerization (e.g., similar to a Berry pseudorotation) of the metal complex, considering that species with a quaternary carbon, as they appear in

• experimentally achievable ee values. Maximal theoretical ee values are 70% "S" for Z-hydrazone and 70% "R" for E-hydrazone. The relatively high racemization barriers in 9 preclude a Curtin–Hammett scenario (with fast pre-equilibrium), which would otherwise render the enantiomeric outcome (ee value) independent

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• generation of chiral secondary alkylcopper species has been a significant challenge in organic synthesis, primarily due to their inherent instability and tendency to racemization [38]. For generating the key chiral organocopper intermediates, two distinct approaches have been developed: one utilizing chiral

• the Li/I exchange is essential for preventing racemization of the configurationally labile organolithium intermediate. The subsequent transmetalation with CuBr·P(OEt)3 introduces P(OEt)3 as a supporting ligand, which plays a vital role in stabilizing the resulting chiral organocopper species 14. A key

• importance of reaction conditions after ZnCl2 addition (Scheme 5). When the reaction mixture was stirred at −30 °C for 1 hour (entry 1 in Scheme 5), the product 19 maintained a high diastereomeric ratio (dr), indicating minimal racemization. However, extending the stirring time or increasing the reaction

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• racemization when treated with inorganic bases [25], which had led us to check the equilibrium between Michael and the retro-Michael reaction (Scheme 1). These observations have prompted us to conduct further research into this reaction for potential applications in the kinetic resolution of these adducts. In

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

• enantioselectivities were achieved. The products showed no thermal racemization at 150 °C, what was supported by a calculated high rotational barrier of 49.9 kcal/mol. The usefulness of chiral phosphoric acids also shows in the atroposelective Pictet–Spengler reaction of N-arylindoles 104 with various aldehydes 105

• enantioselectivities, the authors also calculated the racemization barrier of products 133. It was determined as a class-3 atropoisomer with 30.1 kcal/mol at 90 °C in toluene. The preparation of 133 on a gram scale yielded 75% of the product with a similar level of enantiomeric purity (90% ee). A key step of this

• stereoselectivity (96% ee, >95:5 dr). No racemization was observed after 36 hours at 150 °C in o-xylene. The asymmetric synthesis of arylindolylindolinones 139 or 141 bearing both central and axial chirality was accomplished by a combination of arylindoles 137 or 140 and indolinones 138 with CPA (R)-C22 acting as

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• structure of verrulactone A was later unambiguously confirmed by X-ray crystallographic analysis [160]. Chirality and absolute configurations remained unresolved, where it should be noted that even verrulactones A and B are axially chiral with an assumed significant racemization barrier. At least it has

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• compounds 4a–j were also obtained in very good yields (60–98%, Scheme 2). Since the reaction mechanism proceeding with a Wagner–Meerwein rearrangement does not cause racemization or a diastereomeric mixture and preserves the initial enantiomeric excess in the camphene's fluoroalkoxy derivatives (Scheme 4

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• 50 mmol scale [60]. Little racemization (<7%) of 77 occurred during the reaction. The simplicity of the Kropp protocol resulted in a report in the journal of chemical education [61]. Similar work was reported by Delaude and co-workers [62]. They studied a series of zeolites for the hydrochlorination

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• isomerization and photochemical (only for 13a) isomerization [46]. Compounds 13 showed intrinsic planar chirality and their enantiomers could be separated by HPLC. Notably, upon thermal and photochemical isomerization of these compounds, no Z-isomers were detected and only the racemization took place. Such

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• in the visible region were evident in their CD spectra. Using the Arrhenius and Eyring formalisms, the kinetic parameters for the thermal racemization of 57 and 58 were obtained. The activation free enthalpy (ΔG‡) for the racemization of 57 (ΔG‡298 K = 24.8 kcal mol−1) was ≈1.5 kcal mol−1 larger than

• determined the absolute configurations of these atropisomers through the X-ray crystallographic analyses of (Sa)-59 and (Ra)-60. Surprisingly, heating the enantiomers of 69 and 60 at 80 °C for 3 h resulted in negligible thermally induced racemization. Meanwhile, in O2-free toluene solution under illumination

• , the racemization was observed at 80 °C. Torres et al. performed detailed theoretical calculations and showed that the racemization observed in 59 and 60 is caused by triplet-state photogeneration, which leads to the rotation around the sterically hindered buta-1,3-diene chiral axis [132]. In fact, the

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

• has been used to cure a liquid isoprene polymer in precise digital light processing 3D printing [105]. Recently, Kanbayashi et al. reported that thiol–ene chemistry would not cause racemization of an asymmetric center linked to a pendant vinyl group, which can be particularly valuable for

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• reacted immediately (one-pot procedure) with sodium borohydride to give 4.4. It must be noted that this sequence does not induce racemization and that 4.4 can be stored for months with 0.5% of solid KOH acting as a stabilizer [72]. Then, 4.4 was alkylated with stearyl tosylate to produce 4.5. The two

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• chiral nanographenes. Keywords: chiral nanographene; helicene; racemization barrier; Scholl reaction; single-crystal X-ray diffractometry; Introduction Graphene, an allotrope of carbon, has captured widespread attention since it was first experimentally demonstrated as a monolayer of carbon atoms [1

• determined for the enantiopure helicenes. For compound 12, the racemization barrier was 24.8 kcal mol−1 at 298 K, which provides a racemization half-life (t1/2) of 24.4 h. For compounds 11 and 13, neither racemization nor decomposition was observed by chiral HPLC after heating hexadecane solutions of each

• compound at 200 °C for 5 h, which gives a lower limit to the barrier of racemization of ΔG > 38.3 kcal mol−1 at 473 K. The circularly polarized luminescence (CPL) of these structures were also evaluated with the luminescence dissymmetry factors (glum) values of 4 × 10−4 for compound 11 and 7 × 10−4 for

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

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

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• chirality which exhibits no racemization under action of strong bases [29]. The chiral N–H-containing rimantadine-based ligand (L6) is highly lipophilic and it was successfully used for the kinetic resolution of unprotected racemic amino acids [30]. The examples mentioned above show that the metal–Schiff

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• rotation of the isolated products 43a–h did not show any racemization under the standard reaction conditions. Thereafter, imidazolium salts 45a–d, obtained from imidazole N-oxides 44a–d, provided the desired optically active 3-butoxyimidazole-2-thiones 47a–d in 66–83% yield using triethylamine in pyridine