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

• lactone 26. The Zhang group has extended the chiral metalloradical catalysis to cyclopropanation by the intermolecular reaction between styrenes and ketodiazoacetates [59]. Cyclopropanes were obtained in good yields with high relative and absolute stereocontrol. Properties, such as relatively high earth

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• metal-free methodology delivered synthetically versatile iodinated homoallylic alcohols bearing piperidine motifs and pyrrolidine-fused cyclopropanes. Importantly, the reaction was carried out with high operational simplicity and environmental compatibility under mild reaction conditions. In 2024, Chan

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• conversion of cyclopropane and methyl fluoride into mono-, di-, tri-, tetra-, penta-, and hexafluorinated cyclopropanes is exothermic, except for the all-cis-1,2,3-trifluorocyclopropane (1.2.3-c.c.). Compounds featuring geminal fluorines are particularly stabilized due to anomeric-like nF → σ*CF interactions

• prevents ring interconversion, unlike its larger analogs. It is widely used in pharmaceuticals and has attracted significant interest in medicinal chemistry, particularly when fluorinated [1][2][3][4][5][6]. The highly polar C–F bond in fluorinated cyclopropanes destabilizes the ring and alters its overall

• polarity, with these effects varying based on the amount, position, and orientation of the fluorine substituents [7][8]. Mondal and colleagues have extensively reviewed additional properties of fluorinated cyclopropanes, including the conformational behavior of substituents attached to a fluorinated

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

• heterocycles like saccharin and phthalimide, reacted with 1a and 1b yielding the corresponding N–H insertion products [13][14] (Scheme 1, lower part). In a recent publication, ring opening reactions of so-called D–A cyclopropanes (dimethyl 2-arylcyclopropane-1,1-dicarboxylates 3), initiated by a nucleophilic

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• opportunities for further functionalization. This is illustrated by their chemo- and diastereoselective conversion into densely functionalized cyclopropanes (Scheme 1c). Results and Discussion Based on our preliminary result, we started our study by exploring the reaction between ethyl 4,4-dichloro-2-butenoate

• product in 70% yield with 83:17 dr by decreasing the reaction temperature to 50 °C (Table 2, entry 4). Under the same optimal conditions, compound 8 could be transformed into cyclopropane 17 in 61% yield with 81:19 dr (Table 2, entry 5). It is important to note that (2,2-dichlorovinyl)cyclopropanes

• represent an important class of compounds present in a range of bioactive compounds such as permethrin or alpha-cypermethrin, which are commonly used as insecticides [22][23]. The present transformation provides access to densely functionalized (2,2-dichlorovinyl)cyclopropanes, thus representing a potential

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

• in Fe-catalyzed difunctionalization of alkenes with TBHP resulting in δ-peroxy ketones 126 and δ-peroxy esters 129 (Scheme 43a and 43b). In the case of siloxy cyclopropanes 128 the authors used TBAF as the additive to remove the TMS-protecting group. Oxidation of the resulting anion A with TBHP and

(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

• the synthesis of polysubstituted BCHeps bearing a wide range of different substitution patterns. Their synthesis utilises boronyl radicals generated from diboron compounds by a pyridine cocatalyst to induce the [2σ + 2σ] cycloaddition of cyclopropanes and bicyclobutanes [87]. Similarly densely

• substituted BCHeps were synthesised by Waser and co-workers by photoinduced [2σ + 2σ] cycloaddition of bicyclobutanes and cyclopropanes [88]. Conclusion The last years have seen major progress in

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 and sulfenylation promoted by AlCl3. Dialkyl disulfides 47 were also well tolerated in this Lewis acid-mediated sulfenylation reaction in solvent-free conditions at room temperature. In the same year, a three-component reaction between highly substituted cyclopropanes 49, sulfonamides 25 and N

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

• had occurred, which was attributed to halogen bond complex formation. In 2019, the Murphy group reported the first transformation induced by blue LED irradiation of cyclic and acyclic iodonium ylides (e.g., 6) and alkenes, which generated cyclopropanes 40 in yields up to 96% (Scheme 8) [125]. UV–vis

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

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• , but a dihydrofuran, so the cyclopropane 1b’ reported in the literature [12][13][19] is presumably incorrect [22]. In the cases of donor–acceptor cyclopropanes possessing an electron-donating group such as an alkoxy or amino group, ring expansion caused by an intramolecular attack of nitro oxygen

• researchers studying organic syntheses using functionalized cyclopropanes. Experimental General All reagents were purchased from commercial sources and used without further purification. 1H and13C NMR spectra were recorded on Bruker DPX-400 and JEOL JMN-ECZ400S spectrometers (400 MHz and 100 MHz, respectively

• cyclization reaction using 4e by 1H NMR. Versatile reactivities of cyclopropanes 1a. Preparative methods for cyclopropanedicarboxylates 1a. Bromination of ethyl acetoacetate (3c) and reaction with nitrostyrene 2a. Reaction of 4b with (diacetoxyiodo)benzene (top); structural determination of product 9 (bottom

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -benzothiazol-2-yl(diazo)acetates (Scheme 1, entry 3) [12], dearomative [3 + 2] cycloaddition reactions of benzothiazoles with cyclopropanes (Scheme 1, entry 4) [13][14][15], multicomponent reactions (MCRs) of benzothiazoles, isocyanides and 2-methylidenemalonates (Scheme 1, entry 5) [16], 1,3-dipolar

• -aminothiophenol with donor–acceptor cyclopropanes (Scheme 2, entry 10) [27], condensations of o-aminothiophenol with 4-oxo acids or their derivatives (Scheme 2, entry 11) [2][28][29][30][31] and cascade reactions of o-aminothiophenol, furfural and anhydrides of 2,3-unsaturated carboxylic acids (Scheme 2, entry 12

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• -pentafluoropropylphosphonate, bearing a trifluoromethyl and a difluoromethyl group is reported for the first time. Its application in CuI-catalyzed cyclopropanation reactions with aromatic and aliphatic terminal alkenes under mild reaction conditions is demonstrated. In total, sixteen new cyclopropanes were synthesized in

• good to very good yields. Keywords: alkenes; cyclopropanation; diazo compounds; difluoromethylphosphonate; DFT calculations; Introduction Cyclopropanes constitute a fascinating class of organic compounds due to their unique structure and bond properties [1]. However, their synthetic utility is

• them, trifluoromethyl- and difluoromethyl-substituted cyclopropanes are of great interest in pharmaceutical, materials and agricultural chemistry [3]. Due to the unique properties of fluorine, such as highest electronegativity, small atomic radius, or low polarizability, the strategic placement of

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• cyclopropanes with arenes [29]. They have also been used in Pd-catalyzed cross-coupling reactions to react with hypervalent iodonium salts, organostananes, and vinyl epoxides [30][31][32]. Moreover, there are reports of them serving as oxidizing agents for alcohols [33]. Two papers have recently reported

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• ][26]. Donor–acceptor cyclopropanes constitute an easily available equivalent of all-carbon 1,3-zwitter-ions used in targeted synthesis of various alicyclic as well as carbo- or heterocyclic compounds [27][28][29][30]. The reactive synergy of the three-membered ring and the C–C bond polarization due to

• recently, two publications from the Werz group appeared concerning anodic activation of donor–acceptor cyclopropanes followed by their functionalization with arenes [43] or yielding oxy-ketones or 1,2-dioxanes [44]; the latter process was inspired by a previous report of Buriez [45]. The anodic

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• electrochemical production of cyclopropane derivatives is an environmentally friendly and easy to perform synthetic procedure. Keywords: alkyl 2-chloroacetates; cyclopropane derivatives; divided cell; electro-reduction; Introduction In organic chemistry, cyclopropanes and their related compounds have been

• recognized as important molecules. For example, cyclopropane derivatives are found in both natural products and pharmaceutical products. The cyclopropane skeleton is also found in agrochemicals, especially pyrethroid, as an insecticide, is one important compound. Cyclopropanes also play a significant role in

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP (Scheme 13) [24]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom. Very recently, our group has reported the

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• of the alkyl radical generating the cross-coupled product cannot be ruled out [57][60]. In 2020, Gutierrez and co-workers developed a Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes 14 with alkyl bromides 13 and aryl Grignard reagents 2 (Scheme 4) [61]. Using

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

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

• of fluorinated cyclopropanes was described by Atkinson in 1952 [9], followed by Tarrant [10], and Misani [11]. Tarrant, Lovelace and Lilyquist synthesized 1,1-difluoro-2,3-dimethylcyclopropane (2) by a reductive debromination using zinc metal (Scheme 1) [10]. After 1960 further methods of generating

• difluorocarbenes became available. These methods contributed to the synthesis of a wide variety of fluorinated cyclopropanes. In 2003, two reviews by Dolbier [7] and Fedorynski [8] were published on the methods of synthesis and use of difluorocyclopropanes in organic synthesis. They discussed in detail the various

• difluorocyclopropane and its derivatives can be distinguished: carbene and non-carbene methods of cyclopropanation along with functional group transformations of existing cyclopropanes. The most popular route to prepare fluorocyclopropanes is to generate fluorine-containing carbenes (or carbenoids), which then react

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• are reacted with a C4 donor to form the pyrrole ring; many functional molecules, such as bioderived furans [29], (Z)-enynols [30], 1-vinylpropargyl alcohols [31], doubly activated cyclopropanes [32], and enynals [33], can be used as C4 counter reagents. The carbon-based 1,4-biselectrophiles, such as

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• that the Lewis acid-catalyzed reaction of diaziridines with donor–acceptor cyclopropanes and aziridines affords the perhydropyridazine or triazine derivatives, respectively, in good yields [31][32][33]. The use of microwave irradiation in organic synthesis complies with the principles of green

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• products and subsequent cyclization into fused-ring cyclopropanes. Two new fluoroselenation protocols using PhSeBr/Deoxo-Fluor® and PhSeBr/Et3N⋅3HF, respectively, have been described, but the substrate scope of this reaction was more limited. The transformation of the obtained fluoroselenides into allyl

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

• ][119][120][121][122]. There are many approaches to photosensitized fluorination that do not involve direct C–H activation, which are reviewed elsewhere [123][124][125], such as C–C bond fragmentation/C–F bond formation [126], aminofluorination of cyclopropanes [127] and decarboxylative fluorination

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• ][20][21][22]. However, there is comparatively less precedence of lipophilicity comparisons between fluorinated isopropyl groups, cyclopropanes and oxetanes. Examples of bioactive compounds are given in Figure 2. During the optimization of the LpxC inhibitor 7a [23], it was shown that fluorination to