From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• theme of the different androstane targets was the presence of a cyclopropane moiety in the A-ring. Figure 1 shows two of my favorite molecules synthesized in my work. What fascinated me about these molecules – and I now realize that this was a sign of my physical-organic chemistry leanings – was the

• spectroscopic difference between these molecules and how these compared to analogous steroids whereby the cyclopropane group in the A-ring is replaced with a conjugating C=C double bond. To cut a long story short, vinyl cyclopropanes are conjugated, albeit to a lesser degree than dienes, and NMR, IR and UV–vis

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

• skeleton of crenulatanes, which features an eight-membered carbocyclic ring fused to a cyclopropane ring, may be the product of a photoisomerization of xenicanes. This hypothesis was further supported by the fact that crenulatanes usually co-occur with xenicanes in brown seaweeds of the family Dictyotaceae

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

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

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• halodiazoacetates. The formation of the quinoline structure is probably the result of a cyclopropanation at the 2- and 3-positions of the indole followed by ring-opening of the cyclopropane and elimination of H–X. Keywords: catalysis; cyclopropanation; indole; quinoline; Rh(II); ring expansion; Introduction The

• reactions between pyrrole and chloromethylcarbene, and 2,3-dimethylindole and dichloromethylcarbene [20][21]. It was suggested that the quinoline ring system is formed by ring expension of a labile indoline cyclopropane intermediate. In analogy to the postulated literature pathway, we propose that the

• reactions in our study start by cyclopropanation of the rhodium carbenoid to produce an indoline halocyclopropyl ester. The labile indoline intermediate then undergoes ring opening of the cyclopropane and elimination of H–X to form the quinoline structure (Scheme 3). We attempted to find support for the

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• gain associated to metallacycle formation, already discussed, while E2 is the energy loss due to the hypothetical release of cyclopropane from the Ru–metallacycle species. The larger E1 and E2 values for the 2nd generation system 7 clearly indicate that the Ru–C σ-bonds are stronger in the presence of

• (distance in Å). Representative geometries of the metallacycles 7 and 15, parts a and b, respectively (distance in Å). Energy profiles for systems 1 and 14. Energy profiles for systems 7 and 16. Metallocycle and cyclopropane formation energy profile (energies in kcal/mol). Mechanism of the olefin metathesis

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• cyclopropane derivatives 30 (62%) and 32 (44%). Later, Michael addition in the presence of caesium fluoride and benzyltriethylammonium chloride in DMF gave the benzannulated cyclodecanone derivatives 31 (11%) and 33 (10%) (Scheme 2). Oxymercuration – Hantzsch pyridine synthesis: Kondo and Miyake [86] have

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• as the primary hydrolysis product 6 (Figure 1) is nearly completely depleted. The details of the reaction mixture that yielded diphenyl ether-2,2’-biscyclofenchene 7 (Figure 2) are shown in Scheme 2. The formation of a cyclopropane ring in 7 can be rationalized to proceed through a fenchyl

• hydrolysis, O–BIFOP–Cl (3) reacts instantly with water, leading to cyclofenchene 6. X-ray studies revealed that the increased reactivity of the intermediate carbenium ion and cyclopropane formation is due to a steric effect caused by the shielding of the fenchane groups and a hypervalent P(III)–O interaction

• –BIFOP–H (4), O–BIFOP–(O)H (6) as well as diphenyl ether-2,2’-biscyclofenchene 7. Proposed mechanism for the formation of diphenyl ether-2,2’-biscyclofenchene 7 through stabilization of the intermediate carbocation by O-lp conjugation and cyclopropane formation starting from O–BIFOP–Cl (3). The different

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• with dihalocarbenes to generate SAMs, terminated with dihalo- (fluoro, chloro, bromo) cyclopropane motifs with about 30% surface coverage. Keywords: difluoro-; dichloro-; dibromomethylenecyclopropanes; dihalocarbenes; self-assembled monolayers; surface coating; Introduction Self-assembled monolayers

• reactions were carried out under each of the reaction conditions with dec-1-ene (1, Scheme 1). All of the cyclopropane products 2a-c were obtained cleanly and in moderate yields (see Supporting Information File 1). The results of the model reactions demonstrate that formation of the dihalocyclopropane rings

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• racemic trans-(2-fluoromethylcyclopropyl) iodides 11a–c as alkylating agents for the enolates of (R)-10 and (S)-10 (Figure 2). The initially intended preparations of the three precursors 14a–c to the iodides 11a–c all starting from the known dimethyl trans-cyclopropane-1,2-dicarboxylate (12) [21] through

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• observe acylation on the double bond and not on the cyclopropane ring to give 2-propanone-substituted pentachloronorbornene derivatives 8 (Table 2). The structure of 8a was unambiguously proved by single crystal X-ray analysis (Figure 2). A plausible mechanism involving the initial nucleophilic attack of

• the exocyclic olefin on the acylium ion with concomitant cyclopropane ring opening leading to benzylic cation II followed by its combination with chloride ion leading to 8 is proposed (Scheme 5). Conclusion In summary, we have demonstrated the preparation of a variety of Diels–Alder adducts

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• ,R,R)-47a in the conjugate addition to enones provides the corresponding fused endo,endo-cyclopropane 50a in high diastereomeric excess [51]. The transformation proceeds via the intermediate Michael adduct 49, which eliminates chloride after stereocontrolled attack of the enolate to afford

• cyclopropane 50a. Starting with (cis,R,R)-47b, the isomeric exo,endo product 50b is obtained as major isomer. The cyclopropanation reaction tolerates a wide range of Michael acceptor subtrates such as enones, lactones, lactams, and acyclic α,β-unsaturated esters. The obtained products can easily be cleaved to

• the corresponding aldehydes 51 by ozonolysis, reduced further to alcohols 52, and constitute versatile cyclopropane chirons (Scheme 6) [51][52][53][54][55]. The cyclopropanation with chloroallyl phosphonamide 47a was used to construct the cyclopropane fragments of anthoplalone (8) [56], ambruticin S

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• -DNA molecular platform. In both modifications the torsion around C6’–C7’ within the carbocyclic ring is planarized by either the presence of a C6’–C7’ double bond or a cyclopropane ring. Structural analysis of these two nucleosides by X-ray analysis reveals a clear preference of torsion angle γ for

• structure/nucleic acid affinity profile of this modification we also became interested in nucleoside 11β, containing a double bond instead of the cyclopropane ring. In the context of oligonucleotides this derivative seemed appropriate to investigate the direct steric influence of the cyclopropyl/methylene

• independent proof on the relative configuration around the cyclopropane ring and the glycosidic bond and to obtain insight into the conformational properties of the central bicyclic sugar scaffold, crystals of 8β and 11β were grown and subjected to X-ray analysis (Figure 2, Table 1). It clearly emerges that

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• not from (E)-18. Treatment of 19 with TBAF resulted in cleavage of the TMS protecting group followed by instantaneous elimination of HCl under cyclopropane ring opening to 20 with 16% yield. Furthermore, similar amounts of the fluorinated derivative 21 (17%) were isolated. Its formation is explained

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• ]. Many efforts have been undertaken in the last decades aiming to face and overcome these limitations [1][4][5][6][7][8]. For instance the design of tailored (meth)acrylates based on calix[4]arenes [9][10] or tricyclodecane [11][12] backbones and use of ring-opening monomers as cyclopropane derivatives

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

• the isomerization were identified. It was shown that the nature of this isomerization is different from that demonstrated previously using chiral diphosphine ligands. Keywords: asymmetric catalysis; chiral phosphine ligands; cyclopropane; Heck reaction; organophosphorus; transition metal catalysis

• -equatorial position, whereas the anti-tert-butyl substituent is pseudo-axial; and I2, where this relationship is reversed (Scheme 4). Analysis of these two conformations suggests that steric repulsions between the axial syn-substituent and the methylene group in cyclopropane makes conformation I2

• to avoid the unfavorable steric interaction between the pseudo-axial syn-tert-butyl group and the methylene group of the cyclopropane (Scheme 7). Accordingly, a synergistic steric effect of both the axial P–t-Bu group and a bulky substituent at C4 in dihydrooxazolyl moiety observed in the alternative

Novel indolin-2-one-substituted methanofullerenes bearing long n-alkyl chains: synthesis and application in bulk-heterojunction solar cells

• Irina P. Romanova,
• Andrei V. Bogdanov,
• Inessa A. Izdelieva,
• Vasily A. Trukhanov,
• Gulnara R. Shaikhutdinova,
• Dmitry G. Yakhvarov,
• Shamil K. Latypov,
• Vladimir F. Mironov,
• Vladimir A. Dyakov,
• Ilya V. Golovnin,
• Dmitry Yu. Paraschuk and
• Oleg G. Sinyashin

Beilstein J. Org. Chem. 2014, 10, 1121–1128, doi:10.3762/bjoc.10.111

• phase so that no clear correlation between the AIM solubility and its miscibility with P3HT was observed. We suppose that fine tuning of the fabrication protocol is needed to reveal the potential of AIM for polymer/fullerene solar cells. Experimental Synthesis 1-Methyl-3-(3-cyclopropane[1][9](C60-Ih

• )[5,6]fulleren-3-yl)-indolin-2-one (AIM 1) was synthesized according to ref. [7]. Isatins A 2–9 were obtained by known procedures [11][12][13][14]. The general procedure for synthesis of 1-alkyl-3-(3-cyclopropane[1][9](C60-Ih)[5,6]fulleren-3-yl)-indolin-2-one (AIMs 2–9) was as follows: tris(diethylamino

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• reported to date. The preparation of compound Ib appears challenging due to both the need to control the stereochemistry of three contiguous chiral centers and the presence of a [2.3]-spiro junction connecting the cyclopropane moiety with a highly functionalized azetidine ring. Here, we describe the

• ). Then, a systematic study of the reactivity of compound 17 was undertaken to identify the most efficient method to introduce the cyclopropane ring on the sterically hindered, α,β-unsaturated trisubstituted olefin group. With this goal in mind, both the Corey–Chaykovsky [25][26][27] and the Simmons–Smith

• faces of the terminal olefin group, therefore affording both the trans and the cis pair of diasteroisomers. As expected based on data available in literature [41][42], the reaction was highly diastereoselective toward the formation of the two trans cyclopropane derivatives 20a and 20c. Furthermore, a

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• energies. In the initial nucleophilic attack (Scheme 6), the nucleophile adds to the site with the largest LUMO coefficient (see below for DFT calculations on the LUMO of circumtrindene). This reaction also proceeds with excellent facial selectivity; the cyclopropane ring is formed exclusively on the

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• keteneimines 57 [77] or in [3 + 3] processes with dimethyl cyclopropane-1,1-dicarboxylates 59 [78]. Both these reactions are co-catalyzed, the former by silver triflate and copper bromide and the latter by silver triflate and nickel(II) perchlorate (Scheme 30 and Scheme 31). In [3 + 2]-cycloaddition reactions

• described by Kerr and may proceed on the activated cyclopropane by a stepwise or concerted mechanism [81]. Similar mechanisms could be also operative in the reaction of ylidic species 43 for the synthesis of 60. Good substrate tolerance and moderate to excellent yields are reported. Reactions involving σ

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• 12'' [15], the DVCPR only proceeds via boat-like transition state 9nn' where both vinyl-moieties are in the endo-orientation reagarding the cyclopropane [16]. The other transition states (9xx'/9xn') would result in a cycloheptadiene with at least one E-configured double bond (13/14) after a

• (DMAPP) through 28 to yield 29, (Scheme 6) [40][41][42] the spiro-oxindole 30 was synthesized. The system underwent a cis-aryl-vinyl-cyclopropane rearrangement [43] to give 31 followed by rearomatization in 4–12 hours at room temperature yielding tricycle 32. The formation of the obtained tricyclic

• DVCPR in an approach towards the core skeleton of tiglianes (like phorbol 206, see Scheme 23), daphnanes and ingenanes [169] in 1980 [170]. Starting from α-bromoenone 198 a Corey–Chaykovsky cyclopropanation reaction was achieved to yield cyclopropane 199. The keto-group was removed using a three step

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• -yl)acetate (141) from the furan derivative (E)-methyl 5-hydroperoxy-5-(5-methylfuran-2-yl)pent-2-enoate (140) (Scheme 33) [264]. A simple method was developed for the synthesis of cyclopropane-containing oxodioxolanes 143a–j and is based on the hydroperoxidation of tertiary alcohols 142a–j in an

• acidic medium followed by cyclization of the intermediate hydroperoxides through the ester group (Scheme 34) [265]. This method allows for the use of a nonhazardous 30% hydrogen peroxide solution. However, the authors mentioned that structurally similar tertiary alcohols, without a cyclopropane

Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane with N-vinyl compounds

• Viacheslav A. Petrov and
• Will Marshall

Beilstein J. Org. Chem. 2013, 9, 2615–2619, doi:10.3762/bjoc.9.295

• 3e showed only one set of signals, despite the fact that in the corresponding cyclopropane (prepared by the reaction of compound 3e with PBu3), restricted rotation around the C–N bond was observed [11]. N-vinylimidazole (4) was found to have a different reactivity profile. The reaction of 4 with 1

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• subunit 2.46 upon elimination of water (Scheme 27, path A). Alternatively, the same intermediate (2.46) can be obtained by an ingenious acid catalysed ring opening of the cyclopropane derivate 2.50, which is readily generated from Grignard-addition to the bis-thiophenyl ketone 2.51 (Scheme 27, path B

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• could be formally categorized as a [2 + 1] cycloaddition. In particular, they showed that it is possible to trap the intermediate gold–carbenes resulting from a 1,2-acyloxy migration in propargyl esters such as 1, with external alkenes (e.g. vinylarenes), to give cyclopropane products [41]. The racemic

• variant of the method, which employs Ph3PAuCl/AgSbF6 as a catalyst, predominantly affords cis-cyclopropane adducts of type 2, and tolerates a wide range of olefin substituents. Importantly, the authors demonstrated that the process could also be rendered enantioselective by using a chiral bisgold complex

• with high diastereoselectivity. Moreover, the enantioselective cyclopropanation was not limited to arylated olefins (e.g. styrenes), but allyltrimethylsilane also participated in the process, producing the corresponding silylmethyl cyclopropane as a 5:1 mixture of cis:trans isomers with a good 78% ee

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• cyclopropane unit had not been previously tested under nickel-catalyzed reductive coupling conditions. Nickel(0) is known to catalyze the rearrangement of vinylcyclopropanes to cyclopentenes; however, activating substituents are commonly required [19][20][21]. Furthermore, application of a proposed 1,5

• the trans double bond in the opening of a cyclopropane with an adjacent hydroxy or mesylate leaving group, regardless of the initial configuration of the cyclopropane (Scheme 3, reaction 2) [27]. Braddock has demonstrated that the internal 3,4-E olefin is obtained exclusively in Prins reactions

• terminated by cyclopropylmethylsilane (Scheme 3, reaction 3), which may be explained by the participation of a carbocation that is stabilized by the adjacent cyclopropane ring in the bisected conformation where (CHOR)R′ is oriented anti to the cyclopropane [28][29][30]. Finally, Micalizio has described a

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• ][37][38][39][40][41][42][43][44][45][46][47]. Thus, we believe the reaction follows the pathways shown in Scheme 7 although the possibility of direct formations of 9 and 10, a concerted ET and cyclopropane ring opening, cannot be ruled out. Rapid 5-exo cyclization of hexenyl radical moiety in 9

• from these substrates are strongly influenced by post ring-opening steps. Thus, cyclopropane bond cleavage, which is reversible, does not serve as a product-determining step if a rapid follow-up reaction like hexenyl-radical cyclization does not exist. The results show that by using a proper choice of