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

• byproducts were detected which supports the absence of an initial oxidative addition between the alkyl iodide and the active Fe catalyst. The possibility of a radical process rather than ionic cross-coupling is supported by the tandem cyclization/cyclopropyl ring-opening reaction, similar to previous reports

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• a result, the corresponding norbornene 2m having a cyclopropane ring was obtained in moderate yield (44%). The cycloaddition proceeds much more slowly as a result of the high steric demand of the cyclopropyl ring of the spirodiene compared to the CH2 group of cyclopentadiene. We believe that this is

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 intermediate isocyanate, Scheme 29) [74]. Such transformations proceed with the conservation of the difluorocyclopropane unit and complement the methods for the cyclopropyl-ring synthesis discussed in the previous sections. Generation of fluorinated methylenecyclopropanes: Fluorinated

• compounds were synthesized in this way. The reaction with bromine proceeded through the breaking of the distal bond of the cyclopropyl ring affording the final fluorine-containing compound 140 (Scheme 60) [111]. Cleavage of the proximal bond: Cheng investigated the ring-opening reactions of difluoro

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• cyclopropyl ring H2-22 (δ −0.06 brt, J = 4.8 Hz, δ 0.43 dd, J = 3.9, 9.2 Hz). Furthermore, this spectrum proved the presence of the olefinic proton H-16 (δ 5.49 brs), the downfield shifted methine proton H-11 (δ 5.49 brs), and the hemiacetal hydrogen atom H-19 (δ 5.24 d, J = 4.4 Hz). The 1H NMR spectrum also

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• turn gave intermediate 8.4· upon cyclization onto the methylenecyclopropane double bond. Ring opening of the strained cyclopropyl ring liberated an alkyl radical (in intermediate 8.5·) that readily cyclized onto the adjacent aromatic ring to give 8.6 in a good yield. The oxidation of 8.6 under radical

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• isotope labeling experiments combined with QM calculations. Intermediate G forms via a 1,5-hydride shift from C6 to C10 to generate a homoallylic cation, and the formation of intermediate H occurs due to cyclization to yield a cyclopropyl ring. Intermediate I forms due to isomeric formation of a

• cyclopropylcarbinyl cation, as shown by isotope labeling [41]. QM calculations support this unusual 1,3-alkyl shift that interconverts H and I [38][39]. Finally, the cyclopropyl ring opens by virtue of a nucleophilic water attack, and cyclooctat-9-en-7-ol is formed. Although gas phase calculations shed light on the

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• efficiently chlorinate 6 at the less activated C6 position in the presence of the C7 cyclopropyl group. Treatment of 6 with 12 (1.5 equiv) in DMF at 50 °C for 16–24 h gave the desired chloro product 7 in 77–94% isolated yield. Analysis of the crude reaction mixture showed only trace amounts of cyclopropyl

• ring opened products such as 14/15 as detectible by LC–MS. Hence, 12 proved to be a far superior reagent, when compared to NCS, for the C6 chlorination of thieno[3,2-d]pyrimidine 6 (i.e., 6 → 7). Completion of our synthesis of 1 followed established procedures although it proved expedient to carry

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• alanine, bearing the possibility to stabilize the carbocation, results in 3,7,12-dolabellatriene 6 (Table 2 and Scheme 1). Finally, the cyclopropyl ring is opened by a 1,3-alkyl shift and a subsequent nucleophilic attack by a water molecule at C7 yields the product cycloocat-9-en-7-ol (4). Notably, no

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• (Scheme 2). Cations 6 are stabilized by the cyclopropyl ring and are therefore much more stable than simple primary carbocations. The cyclobutyl cation 7 is also quite stabilized relative to simple secondary carbocations. This cation has been called a “bicyclobutonium” cation, 7a, which is a nonclassical

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• which are caused by the unsaturated character of the cyclopropyl ring. Although cyclopropanols are usually less reactive than enols and enolates, their chemical properties are somehow more diverse as they undergo useful transformations either with preservation or rupture of the cyclic structure [5

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• derivative 29. Indeed, coupling these compounds with cyclopropylboronic acid gave the corresponding cyclopropyl derivatives 14, 18 or 30 in 60, 47 and 75% yield, respectively. The palladium-based reduction of compound 14 and 18 also led to the hydrogenation of their cyclopropyl ring into a propyl side chain

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• insertion to form the caged cyclopropyl ring system in 120. Alternatively, the proximity of the methylene of the benzyl ether in 123 allows for a benzylic C–H insertion to generate the bridged polycycle 124. Tungsten Iwasawa demonstrated a similar strategy for bridged-polycycle synthesis using a tungsten

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• 149 in 55% yield. A highly stereoselective Simmons–Smith reaction [70] delivered the cyclopropyl ring exclusively from the accessible α-face to give 150. The synthesis of (+)-acetoxycrenulide (151) was completed in seven further steps and in summary proceeded in 33 steps (longest linear sequence) and

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• )PdCl2 and (L4)PdCl2 complexes demonstrated that all atoms of the palladacycle, cyclopropyl ring, and both tert-butyl substituents can be almost perfectly superimposed, which for both ligand configurations, confirms the strong preference of a conformation in which the syn-tert-Bu substituent (C14) and

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• cyclopropyl ring opening to generate distonic radical cation 26. The primary carbon radical of 26 adds to the terminal carbon of alkyne 27 to afford vinyl radical 28. Intramolecular addition of the vinyl radical to the iminium ion of distonic radical cation 28 closes the five membered ring and furnishes amine

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• of the reaction; NMP produced much higher yields of the products 89 than DMF, while no products were formed in MeCN or MeOH. The authors interrogated the intermediacy of the α-amino radical 88 by treatment of diphenylmethylaniline with a Michael acceptor incorporating a cyclopropyl ring 95. The ring

Synthesis of 2,6-disubstituted tetrahydroazulene derivatives

• Zakir Hussain,
• Henning Hopf,
• Khurshid Ayub and
• S. Holger Eichhorn

Beilstein J. Org. Chem. 2012, 8, 693–698, doi:10.3762/bjoc.8.77

• inversion centers. Furthermore, a triplet in the 1H NMR spectrum at δ = 1.54 ppm with a coupling constant of 4.2 Hz between the H-atoms at the cyclopropyl ring, indicates an anti-relation between the ethoxycarbonyl group and the cyclohexene ring. The subsequent step comprised the ring opening of 4 to

Perhydroazulene-based liquid-crystalline materials with smectic phases

• Zakir Hussain,
• Henning Hopf and
• S. Holger Eichhorn

Beilstein J. Org. Chem. 2012, 8, 403–410, doi:10.3762/bjoc.8.44

• , diastereotopic with respect to above and below the plane of the molecules. A triplet at 1.40 ppm for 1a and 1.34 ppm for 1b with almost the same coupling constant (4.3 Hz) between the H-atoms at the cyclopropyl ring indicates an anti-relation between the ethoxycarbonyl group and the cyclohexene ring. The isomers

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• majuscula strain found in Curacao, and it exhibits potent antiproliferative and cytotoxic activities [44]. This intriguing structure contains a thiazoline and a cyclopropyl ring. Interestingly, the pathway comprises a HMG-CoA synthase cassette, highly similar to the one of the jamaicamide assembly line

• halogenation domain, although this could not be expected from the structure of curacin A. In vitro studies revealed that indeed cyclopropyl ring formation is preceded by a halogenation step (Figure 6B) [42]. The Cur ECH2 was found to catalyze the formation of a α,β-enoyl thioester, which is in contrast to the

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• containing electron-withdrawing, electron-donating, and sterically demanding substituents. This transformation is thought to proceed through activation of the substituted cyclopropylmethanol by the gold catalyst, which leads to the ionization of the alcohol followed by the subsequent cyclopropyl ring opening

• cyclopropyl ring opening to give carbocation 45, which is then trapped in the presence of an external nucleophile to give, after protonolysis, furans 43 (Scheme 14, path a). Alternatively, gold can complex both of the unsaturated moieties as in 46, triggering the cyclopropyl ring opening through an

• activation of the cyclopropene, cation 55 is formed. C–C bond cleavage of the cyclopropyl ring followed by a Friedel–Crafts reaction affords, after recovery of aromaticity, the observed products [47]. 4 Ring expansions involving annulation reactions Diels–Alder, [1,3]-dipolar-, [2 + 2]- and [4 + 3

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• indeed involved was carried out by Reedich and Sheridan [29]: By incorporating a diazo group into the last formed bond of the cyclopropyl ring in the meta photocycloadduct [30], they would be able to see whether the biradical formed by the extrusion of nitrogen gave the same products as the meta

• numerous applications of meta photocycloaddition in total syntheses show that this reaction can be a very efficient tool to access polycyclic natural compounds. However, the cores directly obtained are usually not useful as such, and cleavage of the cyclopropyl ring must be carried out to access naturally

• occurring polycyclic systems. Many investigations have already been achieved by different research groups to diversify the molecules accessible by this synthetic route: The cyclopropyl ring of the meta product is opened to give either bicyclo[3.3.0]octane or bicyclo[3.2.1]octane derivatives (Scheme 17

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• superelectrophile 22 (Scheme 4) [16]. Initial protonation is assumed to occur at the carboxylic acid group to produce 21 followed by protonation of the cyclopropyl ring to give 22. Protonation at the C1–C2 bond produces a dicationic species with the largest possible charge separation (1,5-dication). Reaction with

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• aminopiperidine derivative bearing a spirocyclic ring on the piperidine moiety. Preparation of the aminopiperidine intermediate was carried out by constructing the cyclopropyl ring prior to assembling the piperidine ring. Keywords: Alogliptin; cyclopropyl ring; DPP-4; piperidine; Introduction Inhibition of

• derivative 9a. Preparation of 9a can be carried out following two strategies e.g. construction of cyclopropyl ring on piperidine moiety (Strategy 1) or vice versa (Strategy 2). While the use of first strategy for the preparation of 9a has been reported in the literature [11], application of other strategy is

• functionalized cyclopropyl ring (step i, Scheme 1) via a conventional C–C bond forming reaction. The reaction proceeded well to afford the functionalized cyclopropane derivative 1 as a result of the formation of two C–C bonds in a single step. Selective reduction of the cyano group of the resulting cyanoester 1