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

• details). In contrast, the use of CsF in dioxane at 70 °C proved to be efficient and selectively provided cyclopropane 9 in good yield, albeit with no diastereoselectivity (Table 2, entry 1). Cs2CO3 was also selective for this cyclization and provided a slight increase in diastereoselectivity, although

• 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

• platform for the synthetic diversification on these important scaffolds. Surprisingly, when the TBAF-mediated cyclization was attempted on bisamide 9 the corresponding cyclopropane 18 was not formed (Table 2, entry 6). The use of other mild bases at different temperatures also resulted unproductive

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

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

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• of 87% and 64%, respectively. Unfortunately, the synthesis of vanillin (4q) was unsuccessful due to undesirable oxidation reactions of the electron-rich arene. The cyclopropane derivative 4r was generated from the cyclopropylmethanol in 53% yield. The acetylene derivative 4s could not be isolated due

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• system [48]. To probe the radical intermediate in the reaction, a radical rearrangement experiment with cyclopropane-derived acid 31 was subjected to the standard conditions, leading to the expected ring opening, alkene-containing nitrile product 32 in 62% isolated yield (Figure 3A). Moreover

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• , providing the corresponding product 3aa in 74% yield. Several control experiments were conducted to gain insight into the reaction mechanism of the electroreductive process. The hydroarylation of cyclopropane-substituted styrene 2l resulted in the formation of ring-opening product 3al’, and the simple

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• to the bromide afforded intermediate Q which underwent ring cleavage to give intermediate R. Subsequent 1,4-addition of the methylene carbon to a second molecule of 15a gave intermediate S which underwent cyclization by attack of the methylene carbon to the bromide to give cyclopropane 33. 3

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• to C60 fullerenes [12]. These amines function as bases, their position next to the aromatic surface is essential to turn on anion–π interactions as soon as substrate 4 is deprotonated. Fullerene derivatization with the Bingel reaction installs a cyclopropane that continues with one or two acid

• ammonium cation. Normalized against the fullerene-free control 18, an electron-withdrawing cyano group on the cyclopropane in 19 gave similarly poor A/D19/18 = 1.5. At constant tether length as short as possible, strong increases in anion–π catalysis were found by further minimizing entropy losses 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

• -(arylthio)succinimides 1 or N-(arylseleno)succinimides 1’’ was developed under a Lewis acid catalysis system. This reaction involves ring-opening of the substituted cyclopropane 49, amination at the C1-site, and thiolation at the C3-site. In the transformation, sulfonamide acted as a nucleophile

• , chalcogensuccinimide as an electrophile, and cyclopropane as a zwitterion component (Scheme 21) [58]. In 2020, a Lewis acid-mediated cyclization of β,γ-unsaturated oximes 51 and hydrazones 52 with N-(arylsulfenyl)succinimide 1 and N-(arylseleno)succinimide 1’’ was extended for the formation of isoxazoles 53 and

• sulfenylation of 2‑alkyn-1-one O‑methyloximes. Lewis acid-promoted 2-substituted cyclopropane 1,1-dicarboxylates with sulfonamides and N-(arylthio)succinimides. Lewis acid-mediated cyclization of β,γ-unsaturated oximes and hydrazones with N-(arylthio/seleno)succinimides. Credible pathway for Lewis acid-mediated

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

• cyclopropane 22a. Interestingly, Hadjiarapoglou also revisited their investigation of iodonium ylide cycloadditions and their associated mechanisms [120], using diphenylketene as a new reaction partner with dimedone iodonium ylide 6 (analogous to earlier work reported by Koser in 1975 [9]). Investigations by

• iodobenzene then generated a strained, cyclopropane-fused bicycle 49 that rearranged into the isolated C–H insertion product 46a. In addition to Neiland’s disclosure of the reactions between iodonium ylides and hydrochloric acid (Scheme 1) [1][102], others have also reported that both strong acids (e.g., TsOH

• EDA complexes between alkenes and iodonium ylides with blue light was believed to induce intramolecular iodocyclobutane formation, followed by cyclopropane formation. These reactions were believed to either involve 1,2-diradicals on the ylide, which could engage the complexed alkene, or to involve

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

• -dicarbonyl compounds are treated with (diacetoxyiodo)benzene and tetrabutylammonium iodide, iodination occurs at the α-position of the nitro group, and the subsequent O-attack of the enol moiety leads to 2,3-dihydrofuran. Cyclopropane was successfully synthesized through C-attack as the acyl group became

• through an intramolecular aza-Wittig reaction, yielding cyclopropane-fused 2-quinolones [2]. A nitro group not only activates substrates and stabilizes the α-anion as an electron-withdrawing group but also acts as a nucleophile, electrophile, and leaving group, exhibiting diverse reactivities [3]. For

• reactive allenes (reaction e), which serve as synthetic intermediates for polyfunctionalized enynes [8]. The ring strain of the cyclopropane ring facilitates the cleavage of the C–C bond, and both cation and anion are stabilized by the adjacent phenyl group and ester functions, respectively (reaction f

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• addition with Grignard reagents Feringa and co-workers realized the tandem conjugate addition of Grignard reagents to 4-chlorocrotonates 46 [42]. The enolate 47, which was formed in this process, underwent an intramolecular nucleophilic substitution to form cyclopropane derivatives. Thioesters, esters as

• of a synthetic chemist, the most remarkable feature of this structure is the highly substituted cyclopropane ring incorporating two all-carbon quaternary centers, while the whole structure contains 7 stereocenters. Xu et al. recently demonstrated their 13-step total synthesis of (−)-peyssonnoside A

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

• closely linked to the substitution pattern of the cyclopropane unit [2]. The prevalence of the biologically active cyclopropyl derivatives, either isolated from natural sources or rationally designed as pharmaceutical agents, has inspired chemists to find efficient methods for their preparation. Among

• in boiling toluene, 42% of the diazo reagent 5 was converted to 6a after only 1 hour of stirring. Thus, to increase the conversion rate, the reaction time was prolonged up to 3.5 h. Indeed, after this time, complete conversion of the diazo reagent 5 was observed and cyclopropane 6a was isolated in 74

• stereochemistry of the main isomer, the 19F,1H-HOESY NMR spectrum of compound 6c was recorded. The spectrum shows direct correlation of one fluorine nucleus of the difluoromethyl phosphonate group with two cyclopropane protons at 1.75 and 2.91 ppm, respectively. Thus, it is conceivable that the major

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• displays a similar backbone as asteriscanolide (2), with an α,β-unsaturated ketone on the eight-membered ring, fused with a γ-butyrolactone and a cyclopentane, onto which a cyclopropane is also grafted [48]. The total synthesis of (±)-naupliolide (97) reported by Ito et al. constituted another example of

• allowed to install the cyclopropane ring thanks to the allylic alcohol. The latter was submitted to Ley oxidation, then deprotection and removal of the obtained alcohol gave the [5-8-5] advanced intermediate 184 (Scheme 36). The stage was set for the further functionalization to synthesize hypoestin A

• cyclopropane 185 was performed with lithium in liquid ammonia in order to introduce the angular methyl group. In the same time, the ketone was reduced into an alcohol, which one was submitted to Barton deoxygenation. The alkene side chain underwent a metathesis reaction with methyl methacrylate to introduce an

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• . This was required to avoid undesired hydrogenation of both the vinyl and the cyclopropane moieties, which both proved sensitive to the action of Raney nickel. A particularly troublesome episode that demonstrates the problems one can encounter in dithiane desulfurizations, was encountered in our labs

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• leaving group at the 3β-position, have a unique feature in their chemical reactions. In these steroids, the breaking of the C3–X bond is facilitated by the formation of a cationic strained cyclopropane intermediate, which is formed by translocation of the C5–π bond electrons to the homoallylic carbon atom

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• group on C6 was introduced after cyclopropane ring-opening, ketone protection, epoxidation and reductive ring-opening of the resulting epoxide. A one-pot β-keto phosphonate formation/Horner–Wadsworth–Emmons reaction with formaldehyde afforded 38, a precursor for the key oxidative dearomatization-induced

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

• ) coordination environment in the form of a Schiff base is considered as a route to electrochemical broadening of the donor–acceptor cyclopropane concept in combination with chirality induction in the targeted products. A tendency to the reductive ring-opening and the follow-up reaction paths of thus formed

• radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis

• acids. One-pot combination of the reductive ring opening and subsequent addition of thiols allows obtaining the cysteine derivatives in practical yields and with high stereoselectivity at the removed β-stereocenter. Keywords: amino acids; cathodic cyclopropane opening; cysteine derivatives; Ni–Schiff

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

• -chloroacetates in Bu4NBr/DMF using a divided cell equipped with Pt electrodes to produce the corresponding cyclopropane derivatives in moderate yields were discovered. The reaction conditions were optimized, the scope and limitations, as well as scale-up reactions were investigated. The presented method for the

• 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

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• at the β-position had a significant impact on the reaction. In general, tertiary radicals (or cations) are more stable than secondary ones and therefore, the additional methyl group seems to have a strong steric effect (Figure 3). If so, tying up the two methyl groups as a cyclopropane ring may

• decrease the steric hindrance at the β-position and improve the reaction. Unfortunately, the arylidene cyclopropane 4 was found to be totally unreactive under both conditions (Scheme 3). However, to our surprise, the arylidene cyclobutane 5 was found to be productive and the corresponding spiro ring

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• reductive amination/cyclization of enantiopure cis-cyclopropane dicarbonyls [26]. The strategy based on azomethine ylide cycloadditions to cyclopropenes enables ready access to a wide range of spiro-fused 3-azabicyclo[3.1.0]hexanes (Scheme 1a). Inspired by our recent achievements, we have focused on

• diastereoselectively with TPC (2a), resulting in the formation of bis-spirocyclic meso compound 3a in which the three phenyl substituents attached to the cyclopropane ring are oriented in the same direction (Scheme 2). This suggests that the diastereomer 3a resulting from the approach of the 1,3-dipole 1 from the less

• cyclopropene 2e led to the formation of the diastereomer with all three substituents (at the cyclopropane ring) oriented in the same direction. A notable substituent effect on the reactivity of cyclopropene dipolarophiles 2 was observed for the reactions between PRP (1) and derivatives of 2,3-diphenylcycloprop

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• hydrogen shift. Indene C can either convert into the final indene 3a via a slow 1,3-migration of the hydrogen atom, or is intercepted by carbene A with the formation of cyclopropane D. The relative rates of these competing processes likely determine the composition of the final product mixture. The

• intermediate D into cycloheptadiene E is an example of a relatively rare reaction of the cyclopropane-ring expansion through a 1,5-C‒C bond migration [15][16][17]. This concerted process is followed by yet another 1,5-migration of the hydrogen atom, leading to the final dimer 2a. The formation of a single

• single diastereomer in high yields. In some cases, indenes were obtained in moderate yields. A plausible mechanism of the observed transformations was proposed which implicates a rare rearrangement of the cyclopropane intermediate as the key step. Dimers 2 bearing alkyl substituents at the nitrogen atom

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

• regioselective cyclization of an indole-tethered donor–acceptor cyclopropane. Indole C5 regioselective epoxide–arene cyclization. Funding We acknowledge the financial supports received from DST-SERB, New Delhi (Grant No. CRG/2018/003021) and Council of Scientific and Industrial Research (CSIR), New Delhi (Grant

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

• sterically hindered tertiary alkyl bromides, the authors were able to favor intermolecular radical addition of the generated alkyl radical 17 to the vinylcyclopropane, outcompeting radical rebound to an aryl Fe species. The incipient radical can then undergo ring-opening of the cyclopropane 18. Work by