Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• development, advanced materials innovation, and fundamental molecular science research. In recent years, controllable/divergent synthetic strategies for organic functional molecules using common starting materials have garnered significant attention due to their high efficiency. This review categorizes recent

• reaction activity and selectivity differentiation, the review provides a systematic analysis of the mechanisms of critical steps through specific case studies. It is hoped that the controllable/divergent synthesis concept will spark the interest of practitioners and aficionados to delve deeper into the

• discipline and pursue novel advancements in the realm of chemical synthesis. Keywords: controllable; divergent; diverse products; switchable synthesis; Introduction In the era of synthetic organic chemistry, divergence can produce stereodivergence (including diastereodivergence and enantiodivergence) [1][2

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• solution into chloroform and controllable release into acidic solution [32]. Very recently, it was found that the receptor L alone can further extract solid Li2SO4 into DMSO solution [33], where sulfate binding is sufficiently strong to drive the solid–liquid extraction. DFT calculations suggest that an

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• , Figure 3). We will now consider what happens when fluorine is introduced across much, or all, of an alkyl chain. The extreme case is a perfluoroalkane, in which every hydrogen is replaced with a fluorine (e.g., I, Figure 4). Perfluoroalkanes are not usually thought of in terms of controllable molecular

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• controllable and regioselective synthesis of indol-3-α-ketoamides and indol-3-amides via the direct double- and monoaminocarbonylation of indole derivatives by using secondary amines [70]. They used Pd(dppf)Cl2 as catalyst system. The indol-3-α-ketoamides were synthesized by adding dppf as ligand, CuI as co

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

• -doped triphenylene derivative 22. In the same year, An et al. reported their investigations regarding chalcogen-doped hexa-peri-benzocoronene (HBC) derivatives and their controllable conversion into hydrocarbon nanographenes by ring contraction of the heteropine moiety [65]. The authors first tackled

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

• application potential in biological systems and interactive "smart" materials that can adjust to environmental variations and respond to external light stimuli in a highly controllable manner. The prospective use of the indigoid photoswitches in photopharmacology [81][82][83][84][85][86] is especially

• appealing due to the possibility of performing the switching within the biooptical transparency window (650–900 nm) [87]. Additionally, significant structural differences (180° flip) between the E- and Z-isomers of the compounds provide a prerequisite of light-controllable geometry control in biomolecular

• isomerization of the indigo derivatives that led to the disassembly of well-shaped vesicles and formation of irregular aggregates. The thermal Z–E relaxation of the indigo scaffold provided the restoration of the vesicle structure. The system contributed to the development of red-light-controllable biomedical

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• delivered without effect to the binding site, where the DNA-binding benzoquinolizinium ligand can then be generated as needed upon irradiation. Notably, the use of light for the activation of photo-controllable DNA ligands offers several advantages because it is easy to apply, traceless, and non-invasive

• , both as photo-controllable DNA binder and as DNA-damaging photosensitizer. Still, some key parameters have to be optimized by variation of the substitution pattern. For example, the water solubility of the styrylpyridine substrates has to be increased, and the excitation wavelength for the

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• cyclization reaction with arylpropynal hydrazones. Also, the reaction of 1-(1,3-diphenylprop-2-yn-1-ylidene)-2-phenylhydrazine 58 as the substrate with N-sulfenylsuccinimides 1 afforded fully substituted pyrazoles 59 in up to 98% yield. In 2021, a solvent-controllable approach for the construction of 3

• cyclization of β,γ-unsaturated oximes with N-(arylthio)succinimide. Synthesis of 4-chalcogenyl pyrazoles via chalcogenation/cyclization of α,β-alkynic hydrazones. Controllable synthesis of 3-thiolated pyrroles and pyrrolines. Possible mechanism for controllable synthesis of 3-thiolated pyrroles and pyrrolines

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• allowed a selective and controllable conversion of NaxPy to the 1,2-diphospholide anion, in which two new C−P bonds could selectively be formed [43][44]. The obtained sodium 3,4,5-triaryl-1,2-diphospholides 7 were isolated in good purity from the reaction mixture by filtration and further washing with a

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• approach have already been realized. For example, some metallopolymer-based systems now enable a controllable release of metal ions by ultrasonication to trigger or catalyze small molecule reactions in solution [16][17][18]. Complementarily, studies on mechanically releasing cargo and unmasking

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• should be controllable by the cathode catalyst and electrochemical parameters. Fortunately, we found that chemoselective reduction of enones 1 can be carried out using different cathode catalysts (Pd/C or Ir/C). Results and Discussion Electroreduction of enones to ketones First, we chose cyclohex-2-en-1

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• ). The reactions were conducted in a Retch MM400 ball mill in a stainless-steel milling jar (1.5 mL) at 30 Hz using one stainless-steel ball (diameter: 5 mm) for 10 min. We used a commercially available temperature-controllable heat gun that was placed directly above the ball-milling jar to control the

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• anthracene and phthalimide guests with unusual and controllable site-selectivity mediated by organopalladium-coordinated hosts in water (Figure 1) [34]. The water-solubility of the coordinated host traced from its ionic form, and the aqueous reaction conformed with the concept of green chemistry. In previous

• limitations as well as developing diverse catalysis systems that would induce controllable site-selectivity. Site-selective Diels–Alder reaction of anthracene and phthalimide mediated by aqueous organopalladium-coordinated hosts A and B. Site-selective Diels–Alder and [2 + 2]-photoaddition reactions between

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• controllable by using enantiomerically pure coupling partners [2]. Such terminal epoxides and aziridines are readily available [3][5], while the corresponding α-lithio ethers can be accessed from enantioenriched α-stannyl ethers [25]. The enantiopure variants await future investigation. Dimerisation of α

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• -workers reported controllable mono- and dichlorooxidation of indoles with hypervalent iodine species in DMF/CF3CO2H/H2O at room temperature, which generated 3,3-dichlorooxindoles and 3-monochlorooxindoles, respectively (Scheme 1, reaction 3) [23]. Apart from these methods, most traditional approaches to 3

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• derivative resulted in unsatisfying yields. Synthesis of compound 3 following known procedures [31][32][33]. The five-step synthesis of m6preQ1 2 from compound 3 required derivatization to make the intermediates soluble in organic solvents for a controllable reaction sequence to reduce the cyano group

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• cyclic ketene acetals [277]. This copolymer also showed a well-controllable reversible UCST behavior in aqueous solutions. In 2020, Zhao et al. reported that by incorporating azobenzene functionalities into polyacrylamide copolymers, the responsive UCST behavior was furthermore tuneable via light

• solution, especially focussing on the LCST transition, we have recently shown that an UCST behavior can also be induced in PDMAEMA brushes, thereby generating a novel approach for controllable in situ nanostructuring on surfaces [300][301]. UCST resulting from biological inspired structures. In addition to

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• complexes. Moreover, they also demonstrated the entropic contribution during the controllable photocyclodimerization of AC. More recently, Inoue, Yang, et al. reported that the AC could be obtained regio- and enantioselectively by the photocyclodimerization, with the aid of β-CD dimers with a defined

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• supramolecule-to-supramolecule transformations, involving functions such as chemical purification, controllable guest uptake and release, and reagent storage along with catalysis [47]. However, neither of the examples in this compilation proved to be reversible. In the present minireview, we highlight the

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• , controllable particle sizes and large uniform pores received much attention [97][98]. One possibility to prepare such carbon spheres with defined particle sizes and pore structures is the nanocasting strategy using silica scaffolds as shown by Fuertes [99]. Nevertheless, due to the complex and high-cost

Formal preparation of regioregular and alternating thiophene–thiophene copolymers bearing different substituents

• Atsunori Mori,
• Keisuke Fujita,
• Chihiro Kubota,
• Toyoko Suzuki,
• Kentaro Okano,
• Takuya Matsumoto,
• Takashi Nishino and
• Masaki Horie

Beilstein J. Org. Chem. 2020, 16, 317–324, doi:10.3762/bjoc.16.31

• temperature for 3 h. The addition of the nickel catalyst 5 and further stirring at room temperature followed. The reactions proceeded smoothly to afford the corresponding formally alternating copolymers in 48–84% yields [28]. The molecular weight of the products was found to be controllable based on the ratio

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• -controllable “ON/OFF” working states. The OFF-state (one of the photoisomer or photocaged structure) “masks” the probe before reaching the target analyte, avoiding unwanted interactions with other abundant species in the “working zone”, or unnecessary consumption with analyte in nontargeted locations during in

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• the guests and in less polar solvent. Furthermore, the controllable complexation between (O-methyl)6-2,6-helic[6]arene and protonated 4,4'-bipyridinium salt could be efficiently controlled by acids and bases. Results and Discussion Synthesis of the hosts and the guests 2,6-Helic[6]arene H1 and its