Showing papers on "Cyclopropane published in 2005"
TL;DR: A cycloaddition strategy for the synthesis of highly enantioenriched 2,5-cis-disubstituted tetrahydrofurans has been developed and Mechanistic studies support an unusual SN2 attack by the aldehyde on the activated cyclopropane.
Abstract: A cycloaddition strategy for the synthesis of highly enantioenriched 2,5-cis-disubstituted tetrahydrofurans has been developed. In the presence of catalytic Sn(OTf)2 or SnCl4, a range of aldehydes will undergo formal [3 + 2] cycloadditions with a scalemic donor−acceptor cyclopropane to form optically active heterocycles. Mechanistic studies support an unusual SN2 attack by the aldehyde on the activated cyclopropane. Through this mechanism, stereochemical information contained in the cyclopropane is effectively transferred to the tetrahydrofuran products.
220 citations
TL;DR: 1-Nitrocyclopropyl esters are versatile building blocks to access the corresponding cyclopropane amino esters and aminocyclopropanes in two and three steps, respectively, from commercially available products.
Abstract: A highly enantioselective (up to 97.5% ee) and diastereoselective (95:5 dr trans/cis) Cu(I)-catalyzed cyclopropanation of alkenes using phenyliodonium ylide generated in situ from iodosobenzene and methyl nitroacetate is reported. The cyclopropanation took place with high enantioselectivity for a wide range of alkenes, and the reaction was performed at room temperature. 1-Nitrocyclopropyl esters are versatile building blocks to access the corresponding cyclopropane amino esters and aminocyclopropanes in two and three steps, respectively, from commercially available products.
141 citations
TL;DR: The 18-electron half-sandwich iron(0) complex [CpFe(C2H4)2] [Li(tmeda)] (1a), which is readily available in multigram quantities from inexpensive starting materials, is shown to be an efficient catalyst for the Alder-ene reaction of various 1,6(7)-enynes.
Abstract: The 18-electron half-sandwich iron(0) complex [CpFe(C2H4)2] [Li(tmeda)] (1a), which is readily available in multigram quantities from inexpensive starting materials (ferrocene, ethylene, Li sand), is shown to be an efficient catalyst for the Alder-ene reaction of various 1,6(7)-enynes. Thereby, the presence of the labile alkene ligands in the ferrate catalyst is essential since the analogous complex [CpFe(CO)2]Na is catalytically incompetent. The cycloisomerizations catalyzed by 1a are compatible with various functional groups and turned out to be highly diastereoselective with regard to the configuration of the newly formed alkenes as well as relative stereochemistry at the ring junction. The alkyne moiety in the substrates may be terminal, silylated, or substituted with various groups, including cyclopropane rings. Likewise, the alkene substructure can be varied to a large extent, with cycloalkenes of ring sizes ≥7 being particularly suitable.
72 citations
TL;DR: An interesting rearrangement of arylvinylidenecyclopropanes having three substituents at the 1- and 2-positions of the corresponding cyclopropane catalyzed by Lewis acids to give 6aH-benzo[c]fluorine derivatives via a double intramolecular Friedel-Crafts reaction.
Abstract: An interesting rearrangement of arylvinylidenecyclopropanes having three substituents at the 1- and 2-positions of the corresponding cyclopropane catalyzed by Lewis acids to give 6aH-benzo[c]fluorine derivatives via a double intramolecular Friedel-Crafts reaction or to give an indene derivative via an intramolecular Friedel-Crafts reaction is described.
72 citations
TL;DR: A novel Bingel monoadduct of La@C82 (mono-A) has been synthesized by the reaction with diethyl bromomalonate in the presence of DBU (Bingel-Hirsch reaction), its structure has been fully determined by NMR spectroscopic and X-ray crystallographic analyses.
Abstract: A novel Bingel monoadduct of La@C82 (mono-A) has been synthesized by the reaction with diethyl bromomalonate in the presence of DBU (Bingel−Hirsch reaction). Its structure has been fully determined by NMR spectroscopic and X-ray crystallographic analyses. The most distinct feature of mono-A is the single bond moiety between the functional group and fullerene cage, which is very different from the cyclopropane moiety in a conventional Bingel adduct of empty fullerenes. Further spectroscopic characterizations and calculations revealed the closed-shell structure of mono-A. Its formation mechanism was discussed according to calculation results.
71 citations
TL;DR: The inter- and intramolecular additions of cyclic amides (nitrogen pronucleophiles) to methylenecyclopropanes proceeded smoothly in the presence of catalytic amounts of Pd(PPh(3))(4), affording the corresponding hydroamination products in good to high yields with high regioselectivities.
Abstract: The inter- and intramolecular additions of cyclic amides (nitrogen pronucleophiles) to methylenecyclopropanes proceeded smoothly in the presence of catalytic amounts of Pd(PPh(3))(4), affording the corresponding hydroamination products in good to high yields with high regioselectivities. The ring opening of methylenecyclopropanes occurred at the distal position of the cyclopropane ring.
69 citations
TL;DR: Trisubstituted (E)-alkene isosteres (TEADIs) and novel cyclopropane amide bond isostEres (CPDIs) were synthesized by aldimine addition and three-component aldIMine addition-cyclopropanation methodologies, respectively, and can serve as beta-turn promoters.
59 citations
TL;DR: A chiral rhodium catalyst, Rh 2 [4S-(4')-FBNAZ] 4, was synthesized and was shown to catalyze the intramolecular cyclopropanation of substituted allylic cyanodiazoacetates.
Abstract: A chiral rhodium catalyst, Rh 2 [4S-(4')-FBNAZ] 4 , was synthesized and was shown to catalyze the intramolecular cyclopropanation of substituted allylic cyanodiazoacetates. Alkenes bearing an electron-deficient substituent including carbonyl and halogens are converted into the corresponding cyclopropanes in high yields with both chiral and achiral rhodium catalysts. The cyclopropane derivatives were generated with an enantioselectivity of up to 91% ee. For the asymmetric intramolecular cyclopropanation, cis-halogen-substituted substrates afforded cyclopropanes with higher enantioselectivities than the corresponding trans diastereomers. However, only moderate enantioselectivities were observed with alkenes bearing electron-donating groups such as alkyls. The cyclopropanation of 3-substituted 2-propenyl cyanodiazoacetates was strongly influenced by steric and electronic factors arising from substituents on the alkenes. For the first time, we demonstrated that the intramolecular reaction of gem-dihaloallylic cyanodiazoacetate afforded highly functionalized gem-dihalocyclopropanes. This reaction is an appealing alternative to the addition of dihalocarbenes to alkenes for the formation of gem-dihalocyclopropanes.
53 citations
TL;DR: The highly diastereoselective zinco-cyclopropanation of chiral allylic alcohols using gem-dizinc carbenoids is described, which leads to the efficient synthesis of orthogonally protected 1,2,3-substituted cyclopropane derivatives.
Abstract: The highly diastereoselective zinco-cyclopropanation of chiral allylic alcohols using gem-dizinc carbenoids is described. The reaction produces three contiguous stereogenic centers, and the resulting chiral cyclopropylzinc derivatives can be trapped with electrophiles with retention of configuration. Simple functional group manipulations lead to the efficient synthesis of orthogonally protected 1,2,3-substituted cyclopropane derivatives.
49 citations
TL;DR: The dicationic palladium-II and platinum-II complexes catalyze a cross-coupling reaction of ethylene with tri-and tetrasubstituted olefins, which can lead to both hydrovinylation and cyclopropanation products.
47 citations
TL;DR: It is demonstrated that the unusual reactivity of cyclopropenes can increase the scope and utility of intermolecular Pauson-Khand reactions.
TL;DR: The purified enzyme is strongly inhibited by cyclopropane-1,1-dicarboxylate, with an inhibition constant of 90 nM, and this is due to the low rate constants for formation and dissociation of the enzyme-inhibitor complex.
TL;DR: Several cyclopropyl containing fatty acids 1a-4a are introduced with which to probe the mechanism of P450s capable of fatty acid hydroxylation, and probes are shown to be capable of distinguishing radical from cationic intermediates due to the rapid equilibration of isomeric cycloallylic cations.
Abstract: [reaction: see text] The mechanism of aliphatic hydroxylation by cytochromes P450 has been the subject of intense debate with several proposed mechanistic alternatives. Various cyclopropyl containing compounds (radical clocks), which can produce both unrearranged and ring opened products upon oxidation, have been key tools in these investigations. In this study, we introduce several cyclopropyl containing fatty acids 1a-4a with which to probe the mechanism of P450s capable of fatty acid hydroxylation. The probes are shown to be capable of distinguishing radical from cationic intermediates due to the rapid equilibration of isomeric cyclopropyl cations. Ring opening of a radical intermediate in an oxidative transformation is expected to yield a single rearranged alcohol, whereas a cation isomerizes prior to ring opening, leading to two isomeric homoallylic alcohols. Oxidation of these probes by P450(BM3) and P450(BioI) gives results consistent with a radical but not a cationic intermediate in fatty acid hydroxylation by these enzymes. Quantitation of the unrearranged and ring opened products gives remarkably homogeneous rates for oxygen rebound of (2-3) x 10(10) s(-1). The effects of introduction of a cyclopropane ring into a fatty acid upon the regiochemistry of hydroxylation are discussed.
TL;DR: It is shown that indeed the activity of CFA synthase requires bicarbonate, and that it is inhibited by borate, a planar trigonal molecule that mimics the structure of bICarbonate.
Abstract: Cyclopropane fatty acid (CFA) synthases catalyze the formation of cyclopropane rings on isolated and unactivated olefinic bonds within various fatty acids; the methylene carbon is derived from the activated methyl group of (S)-adenosylmethionine. The E. coli enzyme is the prototype for this class of enzymes, which include the cyclopropane mycolic acid (CMA) synthases, which are potential targets for the design of antituberculosis agents. Crystal structures of several CMA synthases have recently been solved, and electron density attributed to a bicarbonate ion was found in or near the active site. Because a functional assay for CMA synthases has not been developed, the relevance of the bicarbonate ion has not been established. CFA synthase is 30−35% identical to the CMA synthases that have been analyzed structurally, suggesting that the mechanisms of these enzymes are conserved. In this work, we show that indeed the activity of CFA synthase requires bicarbonate, and that it is inhibited by borate, a planar...
TL;DR: In this article, an enanti-selective chiral separation method based on enantioselective GC and HPLC was developed to provide information about the chemical yields of the cyclopropane derivatives.
Abstract: Different classes of cyclopropanes derived from Meldrum's acid (=2,2-dimethyl-1,3-dioxane-4,6-dione; 4), dimethyl malonate (5), 2-diazo-3-(silyloxy)but-3-enoate 16, 2-diazo-3,3,3-trifluoropropanoate 18, diazo(triethylsilyl)acetate 24a, and diazo(dimethylphenylsilyl)acetate 24b were prepared via dirhodium(II)-catalyzed intermolecular cyclopropanation of a set of olefins 3 (Schemes 1 and 4-6). The reactions proceeded with either diazo-free phenyliodonium ylides or diazo compounds affording the desired cyclopropane derivatives in either racemic or enantiomer-enriched forms. The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetates 28, 30, and 33 were carried out in the presence of the chiral dirhodium(II) catalyst [Rh2{(S)-nttl)4}] (9) in toluene to afford the corresponding cyclopropane derivatives 29, 31 and 34 with up to 37% ee (Scheme 7). An efficient enantioselective chiral separation method based on enantioselective GC and HPLC was developed. The method provides information about the chemical yields of the cyclopropane derivatives, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the inter- and intramolecular cyclopropanation reactions and avoids time-consuming workup procedures.
TL;DR: In this article, meso-chiral porphyrins were synthesized from reactions of 5,15-dibromo-10,20-diarylporphyrins with readily available chiral alcohols and amides via palladium-mediated C-N and C-O bond formations.
TL;DR: The 2-furylcarbenoid reactivity of cis-2-alken-4-yn-1-ones is demonstrated to give the 1,2-difurylethylenes, trans- and cis-1,2 di(2-(5-phenylfuryl))ethene (trans-1 and cis2), in 62% and 23% yields, respectively.
Abstract: The cis-2-alken-4-yn-1-one, 1-phenyl-cis-2-penten-4-yn-1-one (cis-1), readily dimerizes on treatment with weak acid to give the 1,2-difurylethylenes, trans- and cis-1,2 di(2-(5-phenylfuryl))ethene (trans-1 and cis-2), in 62% and 23% yields, respectively. Trimerization of cis-1 to trans,trans-1,2,3-tri(2-(5-phenylfuryl)cyclopropane (4) occurred as a byproduct of treatment with weak acid. These reactions demonstrate the 2-furylcarbenoid reactivity of cis-2-alken-4-yn-1-ones.
TL;DR: In this article, the reaction of electron-deficient cyclopropane derivatives with benzoylmethylenetriphenylarsorane (2) and methoxycarbonylmethylene-triphenylarane (4) was found to form cis,trans-1-methoxy carbonyl-2-aryl-3-benzoyl-7,7-dimethyl-6,8-dioxo-spiro[3,5]nona-5,9-dione (3a-3e) and
Abstract: The reaction of electron-deficient cyclopropane derivatives, cis-1-methoxycarbonyl-2-aryl-6,6-dimethyl-5,7-dioxospiro[2,5]octa-4,8-diones with benzoylmethylenetriphenylarsorane (2) and methoxycarbonylmethylene-triphenylarsorane (4) was found to form cis,trans-1-methoxycarbonyl-2-aryl-3-benzoyl-7,7-dimethyl-6,8-dioxo-spiro[3,5]nona-5,9-dione (3a–3e) and trans, cis,trans-5-[2′-methoxycarbonyl-2′-(triphenylarsoranylidene)acetyl]-6-oxo-3-aryl-tetrahydro-pyran-2,4-dicarboxylic acid dimethyl esters (5a–5c) respectively with high stereoselectivity. The possible reaction mechanisms for the formation of the different products were also proposed.
TL;DR: A user-friendly, one-pot procedure was developed to access racemic as well as enantiomerically enriched cyclopropanes and an enantiomers separation was achieved using gas chromatography on the chiral stationary phase Chirasil-beta-dex.
TL;DR: This work proposes that E239 forms a catalytic dyad with the bicarbonate to perform the proton abstraction necessary in the chemical pathway to the cyclopropane ring and rescues mutants that could not be rescued because of the E239Q mutation.
Abstract: Cyclopropane synthases catalyze the cyclopropanation of unsaturated fatty acid using S-adenosyl-L-methionine as the methylene donor. The crystal structure of three cyclopropane synthases from Mycobacterium tuberculosis showed a bicarbonate ion bound in the active site that was proposed to act as a general base in the reaction mechanism [Huang, C., Smith, V., Glickman, M. S., Jacobs, W. R., and Sacchettini, J. C. (2002) J. Biol. Chem. 277, 11559-11569]. Because the in vitro activity of M. tuberculosis cyclopropane synthases has not yet been reported and because the ligands of the bicarbonate ion are all strictly conserved in cyclopropane synthases, we used the closely related Escherichia coli cyclopropane fatty acid synthase for this study. The putative ligands that share a hydrogen bond with the bicarbonate through their side chains were mutated. H266A, Y317F, E239A, and E239Q mutants were thus constructed and purified, and their catalytic efficiencies were 5.3, 0.7, 0.2, and <0.02%, respectively. C139 that is bound to the bicarbonate by its NH amide had already been mutated to serine in a previous work, and this mutant retains 31% of the activity of the wild-type enzyme. Kinetic analyses and binding studies using spectrofluorimetry showed that these mutations affected the catalytic constant rather than the binding of the substrates. While addition of free bicarbonate had almost no effect on the wild-type enzyme activity, all mutants, with the exception of E239A and E239Q, were rescued by the addition of free bicarbonate. The catalytic efficiencies of the rescued mutants were 85, 16, and 14% for C139S, H266A, and Y317F, respectively. This effect was specific to bicarbonate. The kinetic parameters of the rescued mutants were determined, and it is shown that the rescuing effect is due to an increase in kcat. These data are interpreted by assuming that the E. coli cyclopropane fatty acid synthase specifically binds a bicarbonate ion that is involved in catalysis, as proposed for the M. tuberculosis enzymes, and that mutation of the bicarbonate ligands decreases the affinity for that ion. However, because the E239Q mutation could not be rescued, we propose that E239 forms a catalytic dyad with the bicarbonate to perform the proton abstraction necessary in the chemical pathway to the cyclopropane ring.
TL;DR: In this paper, a diastereo and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes from lithiated aryloxiranes and α,β-unsaturated Fischer carbene complex is described.
Abstract: A diastereo- and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes and cyclopropanecarboxylates from lithiated aryloxiranes and α,β-unsaturated Fischer carbene complexes is described.
TL;DR: The reaction of 2,2-dibromo-1-methyl-cyclopropanecarbonitrile with i-PrMgCl in Et( 2)O/CH(2)Cl(2), which provides the cis-magnesium-carbenoid, which reacts with high retention of configuration with various electrophiles.
TL;DR: In this paper, a cyclopropyl-α-trialkylsilyl alkoxides were formed either by addition of cycloprophyllithiums to acyl-silanes or by adding a vinyllithium to a cyclopsynyl-formyl-symbol.
TL;DR: In this paper, a microwave-accelerated Stille coupling of stannylalkenes represents a fast, convergent synthetic approach toward trisubstituted (E)-alkene dipeptide isosteres.
Abstract: Divergent multi-component reactions (DMCR) involving C-C bond formations can provide large increases in structural diversity and allow the rapid assembly of complex products from readily available starting materials. Cascade hydrozirconation-Zr/Zn transmetalation-imine addition of alkynes represents a versatile methodology for the synthesis of (E)-alkene and cyclopropane dipeptide isosteres. Appropriate substitutions at the sp2-carbon of (E)-alkene peptide isosteres allow a range of Pd-catalyzed cross-coupling reactions, which can be used for the fine-tuning of the conformational and electronic properties of the parent peptide bond mimic. C-C bond formation by microwave-accelerated Stille coupling of stannylalkenes represents a fast, convergent synthetic approach toward trisubstituted (E)-alkene dipeptide isosteres. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.
TL;DR: The reaction mechanism was investigated on the basis of oxygen-18 tracer experiment and the ring-expanding products (N-substituted pyrrolidin-2-ones) were obtained in good yields.
Abstract: We succeeded in activating cyclopropyl amides (monoactivated cyclopropane) through the corresponding imidoyl halides prepared in situ in the presence of 2 equiv of PPh3 and 1 equiv of CX4, and the ring-expanding products (N-substituted pyrrolidin-2-ones) were obtained in good yields. The reaction mechanism was investigated on the basis of oxygen-18 tracer experiment.
TL;DR: A new way of combining chiral auxiliaries and substrate-directable reactions for asymmetric synthesis is described that employs a three-step sequence of aldol-cyclopropanation-retro-aldol reactions for the stereoselective synthesis of enantiopure cyclopropane carboxaldehydes.
TL;DR: In this paper, cyclopropyl silyl ketones were treated with trimethylsilyl trifluoromethanesulfonate as a strong acid having low nucleophilic counter anion.
TL;DR: A new Lewis acid catalyzed ring-opening/cyclization reaction of 2-methoxytetrahydrofuran derivatives 4 leading to gamma-butyrolactones as a key step was possible, from the same substrates 4, to obtain selectively cyclopropane derivatives.
TL;DR: In this article, the multi-component condensation of organozirconocene, aldimine and zinc carbenoid was applied to the stereoselective synthesis of cyclopropane amino acid derivatives.
TL;DR: In this paper, a new asymmetric total synthesis of (-)-malyngolide is described, based on the originally developed catalytic asymmetric IMCP reaction; that is, α-diazo-β-keto sulfone (13) was successfully converted to cyclopropane (12) in 92 % yield with excellent enantioselectivity (97% ee).
Abstract: A new asymmetric total synthesis of (-)-malyngolide is described. This synthesis is based on the originally developed catalytic asymmetric IMCP reaction; that is, α-diazo-β-keto sulfone (13) was successfully converted to cyclopropane (12) in 92 % yield with excellent enantioselectivity (97% ee), and cyclopropane (12) was successfully converted to (-)-malyngolide.