Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -dihydro-α-pyrone derivatives, bearing either a distinctive cyclopropane or furan ring and named brevipolides A–O (1–15), have been isolated from the invasive plant Hyptis brevipes Poit. Their fascinating structural features, and the potent biological activities, including cytotoxicity against an array of

• comprehensive combination of quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data, to have a unique tetrahydrofuran ring instead of the cyclopropane functionality. The absolute configuration of these five compounds were evaluated and all conserved as C6R, C1’S, C2’R

• assay against the cell proliferation of the human hormone-refractory prostate cancer cell line (PC-3). Mohapatra’s strategy to brevipolide H (8) As part of the interest in synthesizing biologically active cyclopropane-containing natural products, Mohapatra and co-workers in 2015 started their attempt to

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

• (Scheme 8). In these cases, the amines are formed by preferential β-elimination [20][21] of lithium methoxide rather than BusNLi2. Synthesis of cyclopropylidene 21 (Scheme 9), suggests a terminal N-Bus-aziridine is capable of being deprotonated by the α-lithio cyclopropane from stannane 11; this contrasts

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• cyclization of substituted cyclopropylcarbinol 94 to 2,4,6-trisubstituted tetrahydropyran 97 was reported by Yadav and Kumar [55]. In this reaction, a homoallylic cation was generated from 94 by the opening of the cyclopropane ring in the presence of TFA, which upon reacting with an aldehyde delivered 2,4,6

• gave the desired THP as a 14:1 mixture of trans- and cis-265 in 80% yield. The trans-265 was obtained as a major isomer, where the reaction proceeded through the 6-membered chair-like transition state 264, and the electrophilic ring opening of cyclopropane by the oxocarbenium ion was believed to

• alkoxycarbenium ion intermediate 282, which is followed by a sequential cyclization to form secondary carbocation 283, which in the presence of fluoride ions affords 284, as shown in Scheme 66. Banerjee et al. explored the reactivity of cyclopropane carbaldehydes 285 with 3-butyn-1-ol in the presence of TiX4 for

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• because the variability of the substituents in the cyclopropane moiety is very high. Cyclopropanation of C60 with diazo compounds At the end of 1991, Suzuki [80] reported the first fullerene-containing derivative obtained by nucleophilic addition of diphenyldiazomethane to C60. The reaction of C60 with

• pincer ligands 57, 58 [102], 59 [103], and 60 [104], or the so-called “bucky ligands” (Scheme 18). In the development of new organometallic C60 compounds that can be used as homogeneous catalysts, new blocks 61 and 62, cross-conjugated through cyclopropane, were synthesized (Scheme 19) [104]. Attaching

• synthesized by a similar technique and containing aromatic groups Ar on the one hand and alkyl groups Alk on the other, bound to the C60 core through a cyclopropane ring, most of which were tested in organic solar elements, is presented in Scheme 29, and the substituents are listed in Table 1 [117][118][119

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

• activity; cyclopropanation; difluorocyclopropane derivatives; synthesis; Introduction The chemistry of cyclopropane derivatives is one of the most intensively developing fields of organic chemistry. In the past decade there have been made many investigations to develop new chemo-, regio- and

• stereoselective methods for the synthesis and transformations of cyclopropane derivatives. These investigations gained a significant interest, because cyclopropane and cyclopropene fragments are present in the structures of many biologically active substances, such as antibiotics, anticancer, and antimycotic

• for the two-phase reaction of chlorodifluoromethane (freon 22, 11) with α-methylstyrene (7) was demonstrated by Barbasiewicz [22] (Scheme 6). The reaction proceeded at room temperature for 4 h with the formation of the cyclopropane derivative 8. Chloro- and bromodifluoroacetate salts as

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• product 145 in 76% yield. The hexacyclic compound 145 was converted to kopsanone (19) in three steps. Miscellaneous In 2012, Wang and co-workers reported a Lewis acid-catalyzed intramolecular [3 + 2] cross-cycloaddition (IMCC) of cyclopropane 1,1-diesters with non-activated alkene to generate bridged [n

• and AIBN to a refluxing solution of cyclopropane 155 afforded 156 in 38% yield. It was subjected to cleavage of the Boc group followed by N-allylation to give 157 in 73% yield over two steps. A ring-closing metathesis of freshly prepared 157 was effected by the second generation Hoveyda–Grubbs (HG II

• mechanism. (C) The completion of total synthesis of kopsanone (19). (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] cross-cycloaddition of cyclopropane 1,1-diesters with alkenes [68]. (B) (5,6-Dihydro-1,4-dithiin-2-yl)methanol 151 used as a versatile allyl

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• the products 4j–m were obtained in good to excellent yields. The acid-labile cyclopropanecarboxaldehyde (2n) could also participate well, and the product 4n was obtained in 77% yield without damage of the cyclopropane structure. Dimethyl acetylenedicarboxylate (3b), 1a and 2a could tolerate the LS-FAS

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

• treatment with t-BuOK in THF under reflux was effective. Unexpectedly, all four halofluorinated diesters produced the same condensed ring cyclopropane derivative (rac)-27 (Scheme 15). The stereochemistry of (rac)-27 was determined using NOESY measurements. Regarding the compounds (rac)-2a,b and (rac)-5a

• , the mechanism is relatively straightforward. Instead of an E2 elimination, these compounds are deprotonated next to the ester group, which is closer to the CHBr unit. Then, the carbanion motif of the formed enolates (rac)-T8a and T8b afford the cyclopropane-fused cyclopentane dicarboxylate (rac)-27

• the carbonyl group of the imide ring closer to the CHX moiety. Finally, an intramolecular nucleophilic attack of the carbanion on the CHX motif closes the cyclopropane ring. Of the two possible pathways, only one is observed, which starts with the removal of the sterically less-hindered proton and

A new method for the synthesis of diamantane by hydroisomerization of binor-S on treatment with sulfuric acid

• Rishat I. Aminov and
• Ravil I. Khusnutdinov

Beilstein J. Org. Chem. 2020, 16, 2534–2539, doi:10.3762/bjoc.16.205

• starting binor-S (2) being recovered unchanged. The reaction of hydrocarbon 2 with hydrochloric acid proceeds with the addition of HCl to the cyclopropane ring and results in the formation of a mixture of mono- and dichloro derivatives, the synthesis of which has been reported [13][14]. When sulfuric acid

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• ]. Bach et al. also found that alkenes 198 can undergo a light-induced rearrangement to cyclopropane 199 in the presence of 185 (Scheme 30b) [88]. They discovered that 199 is configurationally unstable under the reaction conditions and propose that a similar deracemisation mechanism is responsible for the

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

• isopropyl substituent led to larger lipophilicity modulation compared to fluorination of the cyclopropyl substituent. Keywords: aliphatic fluorination; cyclopropane; isopropyl; isostere; lipophilicity; oxetane; Introduction The introduction of small alkyl groups onto bioactive compounds as space filling

• contrast to the result observed for C1 (see above, Figure 3). As discussed in the Introduction, converting acyclic alkanes to cyclopropane equivalents is a frequently used tactic in medicinal chemistry. The pairwise comparison of the isopropyl with the cyclopropyl substructures is best discussed via Figure

• cases, for the same fluorination motif, the cyclopropane derivatives have a lower lipophilicity compared to their acyclic equivalents. It is also useful to compare lipophilicities of acyclic and cyclopropane derivatives in which the isosterism represents conversion of a C–H and C–F bond into a C–C bond

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• complex prepared by treatment of the 1-butyne with Co2(CO)8, afforded the corresponding bicyclic cyclopropane-fused cyclopentenone 74 in high yield and high enantioselectivity (Scheme 43). Conclusion In conclusion, as highlighted in this review, the PKR is still a hot area of chemical research as it

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

• of the cyclopropane ring annelated to the ring A. Unlike other scalaranes, which are most often functionalized at C-12 of ring C, it bears two acetoxy groups at C-11 and C-24 instead. The compound was present in all three samples, supporting the dietary relationship between chromodorid nudibranchs of

• sesterterpene reported with a cyclopropane ring bridging the carbons C-3, C-22 and C-4 in ring A, and an acetoxy group at C-11 instead of C-12 in ring C (Figure 2). All ethyl acetate extracts, as well as the isolated new scalarane, showed antibacterial activity against the Gram-positive bacteria Arthrobacter

• of this compound. In general, scalarane sesterterpenes are bioactive metabolites, mainly isolated from marine sources, such as Dictyoceratida sponges and the nudibranchs that feed on them [7][25][29][33][56]. So far, only six scalaranes containing cyclopropane rings, constructed of C-4, C-19 and C-20

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone. Keywords: [3 + 2]-cycloaddition reactions; donor–acceptor cyclopropanes; ferrocenyl

• separation. Moreover, a mixture of nearly equal amounts of isomeric trans-9m and cis-9m was also observed in the reaction of 5a with ferrocenyl fur-2-yl thioketone (8g). The reaction of the phthalimide-derived cyclopropane 5g with thioketone 8a led to a 4:1 mixture of both isomers cis- and trans-9n. Based on

• thioketones 8 in the presence of a Lewis acid was based on the assumption that the coordination of the catalyst by two ester groups activated the cyclopropane ring and allowed a nucleophilic attack of the C=S group on the benzylic position of the cyclopropane derivative (Scheme 4). The subsequent ring-closure

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• negative dielectric anisotropy. The study gives some guidance into effective structure–property relationships for the design of LCs containing selectively fluorinated cyclopropane motifs. Keywords: dielectric anisotropy; difluorocarbene; organic liquid crystals; selectively fluorinated cyclopropanes

• explore the cyclopropane motif containing fluorine atoms. Selectively fluorinated cyclopropanes have been widely used in pharmaceutical research [11], however, the introduction of fluorinated cyclopropanes into liquid crystal scaffolds has not received much attention. Haufe et al. [12], reported

• aryl ring. So, if the α,β,β-trifluorocyclopropane motif were introduced into an appropriate LC scaffold, it could reasonably induce negative dielectric anisotropy if the dipole associated with the cyclopropane remains oriented perpendicular to the molecular axis. Based on this idea, we report the

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• cyclopropanation. We have screened a series of strongly oxidizing photoredox catalysts and various alkenes, but unfortunately we were thus far unsuccessful in obtaining cyclopropane derivatives (see experimental section). Conclusion We have shown that it is possible to use monochloroacetic acid to form two types

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• temperatures are involved, and the reaction requires relatively longer times compared to the organometallic route. Reaction of metal phosphides with cycloalkanes Cyclopropane easily undergoes nucleophilic substitution reactions because of its high ring strain. Tan et al. [69] reported the preparation of 9-(2

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• applied this methodology to ethyl cyclopropane carboxylate in THF, we were delighted to obtain the desired (relatively volatile) product 9 in modest yield, because in our hands previous attempts to prepare 9 in sufficient amounts by following a literature procedure using NaH (in refluxing THF) [8] had

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• corresponding bromo-cyclopropane 17 [24]. According to the authors, the passage of larger amounts of charge to facilitate product isolation might be responsible for the observed lower asymmetric yields. In 1998, Moutet’s group reported for the first time that transition metal complexes with chiral ligands can

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• stereochemically stable quaternary carbon center [1]. For example, TAA-derived peptides containing a cyclopropane ring and ʟ/ᴅ-dimethyl tartrate showed an α-turn and form 310-helical conformations in higher oligomers [2][3][4]. While, TAA-derived peptides having a tetrahydrofuran ring demonstrated a β-turn type

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• indoline cyclopropane intermediate and elimination of HX. The 4-quinolone-3-carboxylic acid scaffold (Figure 1) is regarded as a privileged scaffold in medicinal chemistry, due to the frequent appearance of this structural subunit in many commercial drugs [16][17][18][19][20][21], and a large variety of

• starts with a cyclopropanation of the indole C2–C3 double bond to form an unstable, non-isolatable indoline cyclopropane carboxylate intermediate. This intermediate is nicely set up for a spontaneous ring expansion and elimination of HX to form 4. After exposing 4 to refluxing ethanol, the desired ethyl

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

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

• necessarily results in the formation of the γ-silyl-stabilized cation 24. This cation is the source of the acetate 21. Alternatively, cation 23 can rearrange by migration of the b bond of the cyclopropane. This leads to the β-silylcyclobutyl cation 25, which can subsequently desilylate to give the minor

• cyclopropylcarbinyl cation 26 rearranges by migration of the a bond of the cyclopropane to give the cyclobutyl cation 27. This cation 27 is different from the γ-silyl-stabilized cation 24 in that the cis-nature of the phenyl and TMS groups in 26 requires that these groups are closer to each other in 27. Shown in

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• to the non-classical cation C, which is a derivative of the 2-norbornyl cation [38]. This system either collapses by deprotonation at the methyl group to longifolene (4), or by deprotonation at C-4 with formation of a cyclopropane ring to longicyclene (5). Starting from B, a 2,7-ring closure and