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

• transformations [1]. The cyclopropane subunit is also present in many biologically important compounds such as pheromones, fatty acid metabolites, unusual amino acids and possess interesting herbicidal, insecticidal, antibiotic, antibacterial, antifungal, antiviral and antitumor activities [2]. For these reasons

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• reaction kinetics and their labeling intensities after metabolic incorporation. To determine the efficiencies by which the derivatives are metabolized to sialic acids, we synthesized and investigated the corresponding cyclopropane derivatives because cyclopropenes are not stable under the analysis

• cyclopropene derivatives were not stable under these conditions, an observation that has also been made by Ye and co-workers [27]. Therefore, we decided to investigate the corresponding cyclopropane derivatives instead. We expected them to be stable under the DMB labeling conditions and during the preparation

• shows the synthesis of the mannosamine derivatives Ac4ManNCp(H2) and Ac4ManNCyc(H2) (H2 indicates the cyclopropane moiety, i.e., the formal hydrogenation of the corresponding cyclopropene) as well as their transformation into the DMB-labeled sialic acids that served as reference compounds for the DMB

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• radical cation C resulting from cyclopropane ring opening reacts with alkyne substrate 2a generating radical D. The intermediate radical D yielded E through intramolecular radical addition. After hydrogen atom transfer (HAT) from complex A, the desired product is obtained with regeneration of the N

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• proceeded smoothly at room temperature, affording the corresponding bicyclic cyclopropane ring-fused lactones and lactams in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). After screening of various catalysts, the Ru(II)-Amm-Pheox complex having an ammonium group proved to be

• ][36]. Diazoacetamides, in particular, diazo Weireb amides were tested in our catalytic system because the resulting cyclopropane products can be easily converted into the corresponding aldehydes, ketones, and alcohols [37][38][39][40][41][42][43][44][45][46][47][48]. Results and Discussion Asymmetric

• spirocyclopropanation product and a functionalized cyclopropane were obtained with high enantioselectivities (Table 1, entries 3 and 4). N-Benzyl-diazoacetamide underwent the asymmetric cyclopropanation reaction affording the corresponding lactam in moderate yield and moderate enantioselectivity (Table 1, entry 5

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• substituent at C1. Whereas conjugation with the phenyl group (R = Ph) provides the driving force for the base-promoted isomerization of 1-benzyl-3,3-difluorocyclopropene (A’, R = Ph) into the corresponding benzylidene(gem-difluoro-cyclopropane) (B’) [18], methylene(gem-difluorocyclopropane) (B’’, R = H) is

• corresponding phosphine 4 (94%) by treatment with trichlorosilane, without affecting the (arylmethylene)cyclopropane moiety (Scheme 4). The great efficiency of the [2,3]-sigmatropic rearrangement of phosphinites 2a–h lacking substituents at C3 is in striking contrast with the reactivity of phosphinites

• conditions, which were optimized for imidate 12a, enabled the formation of p-bromobenzylidene[(N-trichloroacetylamino)cyclopropane] 13a as a single (E)-isomer in 63% overall yield (two steps from the corresponding alcohol). Compound 13a was obtained in lower yield in the absence of a base (21%) or when DMF

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• ; transition metal catalysis; Introduction Far from being considered exotic molecules, cyclopropane derivatives constitute an interesting class of compounds. Indeed, far over 4000 natural products bearing a cyclopropane ring have been discovered [1][2][3], and cyclopropane-containing molecules are recurrent

• in medicinal chemistry [4][5][6]. Likewise, due to its unique structure and bond properties, cyclopropanes have exclusive yet useful synthetic utilities [7], which are closely connected with the substitution pattern. For instance, the presence of vinyl groups directly attached to a cyclopropane ring

• cyclopropanes contrasts with the existence of few straightforward routes for their syntheses. Typical methods rely on the use of reagents containing the required cyclopropane ring, which involve multistep sequences for the installation of adequate functionalization. Thus, Wittig-type olefination with

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• Yu Liu Qiao-Lin Wang Zan Chen Cong-Shan Zhou Bi-Quan Xiong Pan-Liang Zhang Chang-An Yang Quan Zhou Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, P. R. China 10.3762/bjoc.15.23 Abstract The ring-opening/cyclization of cyclopropane

• derivatives has drawn great attention in the past several decades. In this review, recent efforts in the development of oxidative radical ring-opening/cyclization of cyclopropane derivatives, including methylenecyclopropanes, cyclopropyl olefins and cyclopropanols, are described. We hope this review will be

• of sufficient interest for the scientific community to further advance the application of oxidative radical strategies in the ring-opening/cyclization of cyclopropane derivatives. Keywords: cyclopropane derivatives; free radicals; ring-opening/cyclization; Introduction Cyclopropane is a cycloalkane

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• -DNA (6’-diF-bc4,3-DNA). The difluorinated thymidine phosphoramidite building block was synthesized starting from an already known gem-difluorinated tricyclic glycal. This tricyclic siloxydifluorocyclopropane was converted into the [4.3.0]bicyclic nucleoside via cyclopropane ring-opening through the

• inseparable mixture of two diiodo-substituted products was unveiled. The major product was the bicyclic gem-diol 4 and the minor one the corresponding ketone 3. We hypothesize that the α,α-difluoroketone 3 was formed through a cyclopropane ring-opening followed by the addition of the electrophilic iodine in

Gold-catalyzed ethylene cyclopropanation

• Silvia G. Rull,
• Andrea Olmos and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2019, 15, 67–71, doi:10.3762/bjoc.15.7

• transfer; cyclopropane; cyclopropylcarboxylate; ethylene cyclopropanation; ethyl diazoacetate; gold catalysis; Introduction Nowadays the olefin cyclopropanation through metal-catalyzed carbene transfer starting from diazo compounds to give olefins constitutes a well-developed tool (Scheme 1a), with an

• compounds bearing a carboxylate substituent are the most commonly employed carbene precursors toward olefin cyclopropanation, their use with ethylene leads to cyclopropane (Scheme 1b). De Bruin and co-workers have described [4] such product in a minor, secondary reaction (yields <12%) while studying the

• development of a catalytic route for cyclopropane 1, we have not invested efforts in the characterization of such materials. The silver complex Tp(CF3)2,BrAg(thf) [19] (Table 1, entry 3) was not effective toward the aforementioned target, since only 5% of 1 was formed. In this case, the product derived from

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• either by a NIS-mediated or Vorbrüggen nucleosidation yielded in both cases the β-tricyclic nucleoside as major anomer. Subsequent desilylation and cyclopropane ring opening of these tricyclic intermediates afforded the unsaturated 6’F-bc4,3 nucleosides. The successful incorporation of the corresponding

• enlargement via selective cyclopropane ring opening [46][47][48][49]. Consequently, the synthesis started from the previously described bicyclic silyl enol ethers 1α/β (Scheme 1) [50][51]. The two anomers of 1 were individually transformed into the trimethylsilyl (TMS)-protected sugars 2α/β by adapting and

• to the hindrance of the difluorocarbene attack on the double bond. The stereochemistry around the cyclopropane ring (endo vs exo) could be assessed by the characteristic coupling pattern between the fluorine atom and the H-C(1) or C(7) in the endo-tricyclic sugars in the corresponding 1H and 13C NMR

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• benzotropones (Scheme 19) [87]. Firstly, dimethylsulfoxonium methylide addition to 4,5-benzotropone (11) provided the introduction of the cyclopropane ring required for two benzohomoazocines. Beckmann rearrangement of 104 resulted in a mixture of ring expansion products 105 and 106 in nearly equal proportions

• . This lactam mixture was then converted into the desired imidates and the imidates 107 and 108 were separated. Reduction of benzohomoazocine 107 proceeded without cleavage of its three-membered ring, whereas the internal cyclopropane σ bond of 108 underwent cleavage to form 110 (Scheme 19). Paquette’s

• illustrated in Scheme 18 and Scheme 19 (Figure 7) [84][85][86][87][145]. The cyclopropane ring in 192 was reduced to the corresponding dihydroazonine 193. Additionally, Ogliaruso’s group prepared 2,3-benzo-6,7-monohomotropone (189) and trans-2,3-benzo-4,5:6,7-bishomotropone (190) from the nonselective

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• Becquerel, 67087 Strasbourg, France 10.3762/bjoc.13.281 Abstract The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this

• ], organozinc or Grignard reagents [12], Rh [13], and Ru [14] catalysts. Another interesting modification of the alkene component is cyclopropanation. To date, there are a few reported examples in the literature of the cyclopropanation of 3-aza-2-oxabicyclic alkenes [15][16][17]. The addition of a cyclopropane

• the structure against cleavage by nucleoside phosphorylases or hydrolases [18][19]. The addition of a cyclopropane unit could provide further rigidity that could better stabilize the compound, thereby enhancing its biological activity. Both of these reported ring-openings of cyclopropanated 3-aza-2

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• . In contrast to the nucleophilic dimethoxycarbene, the formal transfer of the bis(carbomethoxy)carbene from the sulfur ylide 12 to E-1a leads to the cyclopropane derivative 13 [23] (Scheme 4). The reaction was proposed to occur stepwise via the zwiterrionic intermediate 14. Another example of a

• mixtures of isomeric cyclopropanes were obtained in each case. The trans and cis-isomers of cyclopropane 15 were also obtained in reactions of 2-diazopropane with E-1b and Z-1b, respectively [25]. In that case, the formation of the cyclopropanes was stereospecific. The formation of mixtures of thiolanes of

• cyclopropane derivatives. The treatment of methyl 3-methyl-2-oxodithiobutanoate with diazomethane at −80 °C in hexane/CH2Cl2 afforded the expected 2-sulfanyl-2-isobutanoyl-2,5-dihydro-1,3,4-thiadiazole. After the addition of E-1a and warming of the mixture to room temperature, the corresponding thiolane as the

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• the phosphoryl substituent in these compounds. In the case of cyclopropane 3 the reduction did not occur, since the bulky tert-butyl substituent effectively protected the carboxylate group. Hence, the starting material was recovered. The next cyclopropane 4, which contained the sulfinyl substituent in

• geminal position to the ester group, was subjected to a reaction with phenylsilane using the procedure described above. In this case, to our surprise, no alcohol was detected, but the desulfinylation process occurred exclusively. Cyclopropane 4 was formed by carboxylation of 3 with ethyl chloroformate as

• , in the absence of an α-proton at the sulfinyl group which was conclusive in our former studies, we benefited from 13C NMR analysis. The small value of coupling constant 3JP-C = 4 Hz indicated a trans relationship between the carboxylate and the phosphoryl substituent. Desulfinylation of cyclopropane

Unpredictable cycloisomerization of 1,11-dien-6-ynes by a common cobalt catalyst

• Abdusalom A. Suleymanov,
• Dmitry V. Vasilyev,
• Valentin V. Novikov,
• Yulia V. Nelyubina and
• Dmitry S. Perekalin

Beilstein J. Org. Chem. 2017, 13, 639–643, doi:10.3762/bjoc.13.62

• cycloisomerization in the presence of the cobalt catalytic system CoBr2/phosphine ligand/Zn/ZnI2 giving cyclohexene, diene or cyclopropane structures depending on the type of the phosphine ligand. This unpredictable behaviour suggests that, although the availability of the cobalt catalytic system is appealing, the

• [43]. Next, we employed 1,3-bis(diphenylphosphino)propane (dppp) as a phosphine ligand, which surprisingly led to conversion of 1 into some new isomeric products. The 1H NMR spectra of these products contained a number of signals in the 0.5–0.8 ppm region, which is characteristic for cyclopropane

• protons. On the basis of 1H–1H and 1H–13C correlation NMR spectra as well as GC–MS analysis we had assigned the structures of these products as the cyclopropane derivatives with internal 4 and exocyclic 5 double bonds (Scheme 2). Our spectral data correlate well with that of similar compounds, which were

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• HMBC correlations from resonances of H2-7 and H-8 to C-9. The decaline system was finally confirmed by the heteronuclear long range correlations of the resonances from H3-19. Of the five degrees of unsaturation one is ascribed to a keto function, another one to the cyclopropane ring in the side chain

Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols

• Katrina Tait,
• Oday Alrifai,
• Rebecca Boutin,
• Jamie Haner and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 2189–2196, doi:10.3762/bjoc.12.209

• nucleophiles [30]. The second type of predicted ring opening (type 2) involves the attack of the nucleophile at the external cyclopropane carbon B, resulting in the cleavage of the cyclopropane C–C bond followed by a C–O bond cleavage to produce 2-substituted dihydronaphthalenols 10. Under thermal conditions

• nucleophile at the internal cyclopropane carbon C, which could induce ring expansion to form seven-membered ring 12 . In this paper, we aim to explore the use of a palladium catalyst with an alcohol nucleophile on the ring opening of cyclopropanated oxabenzonorbornadiene with the goal of determining which

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• unveiled their ability to act as C and N nucleophiles [5][6][7][8]. In 1981, McCoy and Mal first isolated an adduct of DBU with dimethyl 1-chloro-3-methyl cyclopropane-1,2-dicarboxylate during the dehydrohalogenation of halocyclopropanes [9]. In 1993, Bertrand and co-workers, showed that DBU and DBN act as

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• as strained as cyclopropane or cyclobutane (norbornene, 100 kJ/mol; cyclopropane, 115 kJ/mol; cyclobutane, 110 kJ/mol) [4][5]. Some of the annulated norbornene derivatives undergo retro Diels–Alder (rDA) reactions at ambient temperature in the presence of methylaluminium dichloride and a reactive

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• /C-7, giving evidence for the connectivities of the methyl groups. Further HMBC correlations between H-2 and C-1, C-3, C-5, C-6 and C-10 together with the highfield proton signals at 0.35 ppm (H-6) and 0.71 ppm (H-5) revealed a cyclopropane moiety. The relative configuration of 3 was determined by

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• decomposition of 2c gave a complex mixture and only a trace of the cyclopropane could be seen in the 1H NMR spectrum of the crude product. The Rh2(esp)2-catalyzed reactions in CH2Cl2 gave dramatically lower yields compared to the reactions in toluene [11]. The yields from the thermal reactions were only

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• electron from one of the oxygen lone pairs, but in the special case of epi-cubebol that contains a 3-membered ring the ionisation step may also proceed with removal of an electron from the energetically high molecular orbitals of the cyclopropane moiety, resulting in 3b+·. Neutral loss of the isopropyl

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• ]. However, it is difficult to apply the catalytic system for the regio-controlled reaction with C=C bonds in α,β-unsaturated carbonyl compounds, particularly enals. The highly active aldehyde functionality reacts more favorably with the D–A cyclopropane resulting 1,3-dipoles, as elegantly demonstrated by

• tolerated with good yield and 97% ee for the major product (Table 3, entry 12). More significantly, the more steric demanding D–A cyclopropane bearing a phenyl ring instead of H can effectively participate in the process to deliver the desired product with achieving an excellent level of enantioselectivity

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• tertiary carbocation is trapped by a gold carbenoid intermediate to form the fused cyclopropane. While there had been reports of utilizing chiral ruthenium complexes for asymmetric catalysis prior to our studies [30][31][32][33][34][35][36][37][38][39][40], there had previously been no reported examples of