Showing papers on "Cyclopropane published in 2013"
TL;DR: The borylation of cyclopropanes catalyzed by the combination of (η(6)-mes)IrBpin3 or [Ir(COD)OMe]2 and a phenanthroline derivative is reported, which results in versatile synthetic intermediates that can be converted to trifluoroborate salts, boronic acids, Cyclopropylarenes, cyclopropylamines, andcyclopropanols.
Abstract: The borylation of cyclopropanes catalyzed by the combination of (η6-mes)IrBpin3 or [Ir(COD)OMe]2 and a phenanthroline derivative is reported The borylation occurs selectively at the methylene C–H bonds of the cyclopropane ring over methine or methyl C–H bonds High diasteroselectivities were observed from reactions catalyzed by the combination of iridium and 2,9-Me2phenanthroline The cyclopropylboronate esters that are generated are versatile synthetic intermediates that can be converted to trifluoroborate salts, boronic acids, cyclopropylarenes, cyclopropylamines, and cyclopropanols
120 citations
TL;DR: The chemical behavior of cyclopropyl-substituted alkynes has been probed using the reaction conditions of ruthenium-catalyzed oxidative C-H/O-H and C- H/N-H bond functionalizations and the connectivities of the key heterocyclic products were unambiguously established by X-ray diffraction analysis.
Abstract: The chemical behavior of cyclopropyl-substituted alkynes has been probed using the reaction conditions of ruthenium-catalyzed oxidative C–H/O–H and C–H/N–H bond functionalizations. The oxidative annulations proceeded with complete conservation of all cyclopropane fragments and allowed for the one-step preparation of synthetically useful cyclopropyl-substituted isocoumarins and isoquinolones with high regioselectivities and chemical yields. The connectivities of the key heterocyclic products were unambiguously established by X-ray diffraction analysis.
105 citations
TL;DR: Although there have been some recent successes in this area, several important types of acceptor/acceptor-substituted diazo reagents remain challenging for asymmetric olefin cyclopropanation.
Abstract: Cyclopropanes are a unique class of structure elements found in a number of biologically important compounds and have been demonstrated for a wide range of fundamental and practical applications.[1] One particularly attractive strategy for enantioselective synthesis of chiral cyclopropanes is based on transition metal-catalyzed asymmetric olefin cyclopropanation with diazo reagents.[2] In principle, chiral cyclopropane derivatives with all substitution patterns may be accessible in enantioenriched form by asymmetric cyclopropanation due to the diverse availability of both alkenes and diazo reagents. Among different classes of diazo reagents with various combinations of α-substituents, many acceptor- and donor/acceptor-substituted diazo reagents have been successfully employed as effective carbene sources for metal-catalyzed asymmetric cyclopropanation.[2] In contrast, the capacity of catalytic asymmetric cyclopropanation has not been fully explored with acceptor/acceptor-substituted diazo reagents, which would afford synthetically useful cyclopropane compounds bearing geminal electron-withdrawing functionalities.[3,4] Although there have been some recent successes in this area,[5–9] several important types of acceptor/acceptor-substituted diazo reagents remain challenging for asymmetric olefin cyclopropanation.
87 citations
TL;DR: Developing efficient and general strategies to construct skeletally complex and diverse polycyclic skeletons is important for both synthesis of natural products and chemical biology research.
Abstract: The title reaction is successfully developed, and applied to the total synthesis of the tetracyclic diterpenoids phyllocladanol (XX) and phyllocladene (XXI).
86 citations
TL;DR: The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway.
76 citations
TL;DR: The mechanism, solvent effects, and origins of selectivities in Ru(II)-catalyzed intramolecular (5+2) cycloaddition and ene reaction of vinylcyclopropanes (VCPs) and alkynes have been studied using density functional theory.
Abstract: The mechanism, solvent effects, and origins of selectivities in Ru(II)-catalyzed intramolecular (5+2) cycloaddition and ene reaction of vinylcyclopropanes (VCPs) and alkynes have been studied using density functional theory. B3LYP/6-31G(d)/LANL2DZ optimized structures were further evaluated with the M06 functional, 6-311+G(2d,p) and LANL2DZ basis sets, and the SMD solvent model. The favored mechanism involves an initial ene-yne oxidative cyclization to form a ruthenacyclopentene intermediate. This mechanism is different from that found earlier with rhodium catalysts. The subsequent β-hydride elimination and cyclopropane cleavage are competitive, determining the experimental selectivity. In trans-VCP, the cyclopropane cleavage is intrinsically favored and leads to the (5+2) cycloaddition product. Although the same intrinsic preferences occur with the cis-VCP, an unfavorable rotation is required in order to generate the cis-double bond in seven-membered ring product, which reverses the selectivity. Acetone solvent is found to facilitate the acetonitrile dissociation from the precatalyst, destabilizing the resting state of the catalyst and leading to a lower overall reaction barrier. In addition, the origins of diastereoselectivities when the allylic hydroxyl group is trans to the bridgehead hydrogen are found to be the electrostatic interactions. In the pathway that generates the favored diastereomer, the oxygen lone pairs from the substituent are closer to the cationic catalyst center and provide stabilizing electrostatic interactions. Similar pathways also determine the regioselectivities, that is, whether the more or less substituted C-C bond of cyclopropane is cleaved. In the trans-1,2-disubstitued cyclopropane substrate, the substituent from the cyclopropane is away from the reaction center in both pathways, and low regioselectivity is found. In contrast, the cleavage of the more substituted C-C bond of the cis-1,2-disubstituted cyclopropane has steric repulsions from the substituent, and thus higher regioselectivity is found.
76 citations
TL;DR: Under microwave irradiation, cyclopropane hemimalonates undergo rapid conversion to butanolides in the presence of inorganic salts with an unprecedented retention of stereochemistry, which has been applied to the total synthesis of the naturally occurring (R)-dodecan-4-olide.
63 citations
TL;DR: Two similar-sized N-heterocyclic carbene (NHC) ligands yielded reversed product selectivity, favoring the (5 + 2) and homo-ene products respectively, attributed to the anisotropic steric environment of these NHC ligands.
Abstract: The mechanism and origins of selectivities in [Ni(NHC)]-catalyzed intramolecular (5 + 2) cycloadditions and homo-ene reactions of vinylcyclopropanes (VCPs) and alkynes have been studied using density functional theory. The preferred mechanism involves oxidative alkyne–alkene cyclization to form a metallacyclopentene intermediate, in contrast to a cyclopropane cleavage pathway in the reaction with Rh(I) catalysts. The selectivity between the (5 + 2) and homo-ene products is determined in the subsequent competing reductive elimination and β-hydride elimination steps. Two similar-sized N-heterocyclic carbene (NHC) ligands, SIPr and ItBu, yielded reversed product selectivity, favoring the (5 + 2) and homo-ene products respectively. This is attributed to the anisotropic steric environment of these NHC ligands, which positions the bulky substituents on the ligand toward different directions and leads to distinct steric control in the reductive elimination and β-hydride elimination transition states.
63 citations
TL;DR: The first trans-selective [3 + 2]-cycloaddition of a new type of donor-acceptor cyclopropane with aldehydes is presented and allows for an easy access to tetrahydrofurans bearing a versatile alkyne substituent at the quarternary 2-position under very mild reaction conditions.
59 citations
TL;DR: Carboxylate assistance enabled efficient and chemoselective ruthenium(II)-catalyzed hydroarylations and hydroalkenylations of highly strained methylenecyclopropanes via C-H bond activation occurring with ring conservation of the cyclopropane moieties.
50 citations
TL;DR: In this article, a variety of cycloheptapyrane derivatives were prepared via Ni-catalyzed formal [8+3] cycloaddition of tropones with 1,1-cyclopropanediesters.
TL;DR: Only a few catalytic systems can catalyze the asymmetric cyclopropanation of electron-deficient olefins, such as a,b-unsaturated carbonyl compounds.
Abstract: Transition-metal-catalyzed asymmetric cyclopropanation of olefins with diazoacetates is a highly useful synthetic transformation for the construction of optically active cyclopropane frameworks, which are important structures because of their appearance in a wide variety of biologically active molecules. Therefore, during the past two decades, various catalytic systems have been developed for the highly diastereoand enantioselective cyclopropanation reactions. In particular, good stereocontrolled syntheses of cyclopropane derivatives have been achieved using copper, rhodium, ruthenium, and recently cobalt as catalysts. However, despite these considerable advances, only a few catalytic systems can catalyze the asymmetric cyclopropanation of electron-deficient olefins, such as a,b-unsaturated carbonyl compounds. Because of the electrophilic nature of the metal–carbene intermediate obtained by the reaction of metal complexes and diazoacetate, electron-rich olefins are generally preferred as reactants (Scheme 1).
TL;DR: This new process provides convenient and efficient access to indanes and other cyclopentannulated (hetero)arenes, among which polyoxygenated 1-arylindanes exhibit significant cytotoxicity against several cancer cell lines.
Abstract: Quo vadis? The Lewis acid catalyzed reaction of (hetero)aryl-derived donor-acceptor cyclopropanes with alkenes can be selectively directed along a [3+2] annulation pathway (see scheme). This new process provides convenient and efficient access to indanes and other cyclopentannulated (hetero)arenes, among which polyoxygenated 1-arylindanes exhibit significant cytotoxicity against several cancer cell lines with an IC50 of 10(-6)-10(-5) M.
TL;DR: In this article, the authors investigated the ring-enlargement and rearomatization of donor-acceptor cyclopropanes initiated by Bronsted acids, and found that more substituted substrates led to annelation whereas less substituted substrate compounds tend to undergo rearOMatization.
TL;DR: A visible-light-promoted, tin/boron-free intermolecular [3+2] atom-transfer radical cyclization reaction was developed by using iridium polyphenylpridinyl complex as the sensitizer.
Abstract: Radical chemistry! A visible-light-promoted, tin/boron-free intermolecular [3+2] atom-transfer radical cyclization reaction was developed by using iridium polyphenylpridinyl complex as the sensitizer. 2-(Iodomethyl)cyclopropane-1,1-dicarboxylate reacted with various alkenes and alkynes to form cyclopentane and cyclopentene derivatives.
TL;DR: The AlCl3-promoted [3 + 2]-annulations with aldehydes protocol provides a facile and highly stereoselective way to construct synthetically useful pentasubstituted tetrahydrofurans not easily accessible using other methods.
Abstract: A series of cis-2,3-disubstituted cyclopropane 1,1-diesters were examined in the AlCl3-promoted [3 + 2]-annulations with aldehydes. In this reaction, these cis-cyclopropanes displayed reactivities starkly different from their trans counterparts in terms of the high chemical yields (up to 98%) and provided the desired annulation products with excellent diastereomeric purity. This protocol provides a facile and highly stereoselective way to construct synthetically useful pentasubstituted tetrahydrofurans not easily accessible using other methods.
TL;DR: The enantioselective total synthesis of (+)-colletoic acid, a potent naturally occurring 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, is described.
TL;DR: In this article, a gold-catalyzed oxidative cyclopropanation of 1,6-enynes derived from propiolamides employing diphenyl sulfoxide as an oxidant was proposed.
Abstract: We have developed gold(I)-catalyzed oxidative cyclopropanation of 1,6-enynes derived from propiolamides employing diphenyl sulfoxide as an oxidant. 1,6-Enynes having a terminal alkyne and a propiolamide tether efficiently transformed into cyclopropane carboxaldehyde derivatives.
TL;DR: A novel Lewis acid promoted formal intramolecular [3 + 2] parallel/cross-cycloaddition of cyclopropane 1,1-diesters with allenes has been successfully developed, in which the two C═C of allenes were involved respectively.
TL;DR: The design plan for the synthesis of the scaffold was to effect a tandem process initiated by conjugate addition of an unsaturated amine to vinyl sulfonium salt, generated in situ from the stable and crystalline salt 3 (Scheme 1).
Abstract: Sven P. Fritz, Johnathan V. Matlock, Eoghan M. McGarrigle,* and Varinder K. Aggarwal* The 3-azabicycloACHTUNGTRENNUNG[3.1.0]hexane is a common motif in natural products. Furthermore this rigid framework represents a privileged class of pharmacologically active compounds, often showing enhanced binding affinities with their targets (Figure 1). These bicycles also represent conformationally restricted analogues of piperidines (e.g. trovafloxacin). When substituted with a carboxylic acid moiety, they resemble conformationally restricted analogues of glutamate, gamma-amino butyric acid (GABA) or a/b-proline analogues (Figure 2). Numerous methods have been developed for the construction of azabicyclo ACHTUNGTRENNUNG[3.1.0]hexanes.[10] These include the Kulinkovich/de Meijere reaction, 12] cyclisation of tethered amines with metals (Pd, Ru, Rh, Ag), cyclisation of tethered cyclopropanes and the Simmons–Smith/ Corey–Chaykovsky/sulfur ylide–Au cyclopropanations. These methods are usually only effective in the synthesis of one specific type of scaffold. We were keen to develop a general strategy that could deliver 3-azabicycloACHTUNGTRENNUNG[3.1.0]hexanes with a range of functional groups in a range of positions. Our design plan for the synthesis of the scaffold was to effect a tandem process initiated by conjugate addition of an unsaturated amine 1 to vinyl sulfonium salt 2, generated in situ from the stable and crystalline salt 3 (Scheme 1). The intermediate sulfur ylide 4 would undergo intramolecular addition to the Michael acceptor to give a sulfonium enolate 5, which would ring-close to the cyclopropane 6. This tandem process is related to the previously described reactions that bear aldehydes or imines in place of Michael
TL;DR: In this article, a bicyclo[3.3.1]nonane derivative of hyperforin was synthesized by a three-step sequence: intramolecular cyclopropanation, construction of the C8 all-carbon quaternary stereogenic center, and subsequent regioselective ring opening.
TL;DR: An efficient synthesis of tetramic acid derivatives was developed via intramolecular sp( 3) C-H aminations of 1-acetyl N-aryl cyclopropane/cyclopentanecarboxamides in the presence of PhI(OPiv)(2) and CH(3)CH(2)COOH.
Abstract: An efficient synthesis of tetramic acid derivatives was developed via intramolecular sp3 C–H aminations of 1-acetyl N-aryl cyclopropane/cyclopentanecarboxamides in the presence of PhI(OPiv)2 and CH3CH2COOH.
TL;DR: The (6'S)-configuration of brevipolides A-J (1-10), isolated from Hyptis brevipes, was established by X-ray diffraction analysis of 9 in conjunction with Mosher's ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations.
Abstract: The (6′S)-configuration of brevipolides A–J (1–10), isolated from Hyptis brevipes, was established by X-ray diffraction analysis of 9 in conjunction with Mosher’s ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations. The structure of the new brevipolide J (10) was characterized through NMR and MS data as having the same 6-heptyl-5,6-dihydro-2H-pyran-2-one framework possessing the cyclopropane moiety of all brevipolides but substituted by an isoferuloyl group instead of the p-methoxycinnamoyl moiety found in 8 and 9. Conformational analysis of these cytotoxic 6-heptyl-5,6-dihydro-α-pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT-calculated vicinal 1H–1H NMR coupling constants. Molecular modeling was used to correlate minimum energy conformers and observed electronic circular dichroism transitions for the isomeric series of brevipolides. Compounds 7–10 exhibited mode...
TL;DR: The reaction with the cis-cyclopropanes proceeded to completion within minutes, providing a variety of densely substituted diastereomerically pure 2-iminodihydrothiophenes in moderate to excellent yields.
Abstract: cis-2,3-Disubstituted cyclopropane 1,1-diesters were found to be much more reactive than their corresponding trans-isomers in the AlCl3-promoted [3 + 2]-annulations with isothiocyanates. The reaction with the cis-cyclopropanes proceeded to completion within minutes, providing a variety of densely substituted diastereomerically pure 2-iminodihydrothiophenes in moderate to excellent yields.
TL;DR: A highly effective acid-catalyzed cyclopropyl ester to γ-lactone skeletal rearrangement has been demonstrated and applied to the synthesis of a variety of bi- and tricyclic functionalized lactones, rigid and highly compact structures for use as biological probes.
TL;DR: The synthesis and characterisation of copper(I) complexes of chiral pyridine-containing macrocyclic ligands (Pc-L*) and their use as catalysts in asymmetric cyclopropanation reactions are reported.
Abstract: The synthesis and characterisation of copper(I) complexes of chiral pyridine-containing macrocyclic ligands (Pc-L*) and their use as catalysts in asymmetric cyclopropanation reactions are reported. All ligands and metal complexes were fully characterised, including crystal structures of some species determined by X-ray diffraction on single crystals. This allowed characterising the very different conformations of the macrocycles which could be induced by different substituents or by metal complexation. The strategy adopted for the ligand synthesis is very flexible allowing several structural modifications. A small library of macrocyclic ligands possessing the same donor properties but with either C1 or C2 symmetry was synthesized. Cyclopropane products with both aromatic and aliphatic olefins were obtained in good yields and enantiomeric excesses up to 99%.
TL;DR: In this paper, the first utilization of acyclic cyclopropane bearing spirocyclic olefines for the generation of stereospecific complex fused ring systems with an achiral catalyst was reported.
Abstract: The first utilization of acyclic cyclopropane bearing spirocyclic olefines for the generation of stereospecific complex fused ring systems with an achiral catalyst is reported.
TL;DR: A novel cycloisomerization cascade process consists of a nucleophilic addition followed by a cyclopropane ring-opening, where both donor and acceptor groups are required as substituents of the cycloprostane ring.
TL;DR: The shielding pattern arising from the cyclopropane and cyclobutane CC framework response to a perpendicular magnetic field was visualized as two-dimensional grid distribution of NICS values and insight into the origin of chemical shift values was obtained by the NCS-NBO analysis of proton shielding tensor.
Abstract: This study was undertaken in order to rationalize the peculiar (1)H NMR chemical shifts of cyclopropane (δ 0.22) and cyclobutane (δ 1.98) which are shifted upfield and downfield with respect to larger cycloalkanes (δ 1.44-1.54). This is conventionally accounted for by shielding contributions arising from an aromatic-like ring current in cyclopropane, involving six electrons in the three C-C bonds, and deshielding coming from the σ antiaromatic CC framework of cyclobutane. The shielding pattern arising from the cyclopropane and cyclobutane CC framework response to a perpendicular magnetic field was visualized as two-dimensional grid distribution of NICS values. Further insight into the origin of chemical shift values was obtained by the NCS-NBO analysis of proton shielding tensor. In the case of cyclopropane, the CC framework shielding pattern implies the existence of both delocalized and localized currents that have a dominant shielding effect on protons. The magnitude of C-H bonds shielding effect is significant, too. Unlike the conventional interpretation, the CC framework shields cyclobutane hydrogens, and its response to a perpendicular magnetic field is quite similar to responses of other planar σ CC frameworks.
TL;DR: In this article, a stepwise and rational synthesis of functionalized trans-A2B2-porphyrins is reported in which for the first time donor-acceptor-substituted cyclopropane precursors (d-a cyclopanes) are exploited.
Abstract: meso-Substituted trans-A2B2-porphyrins bearing specific patterns of substituents are crucial building blocks in porphyrin-based biomimetic systems and molecular materials and can be used for the construction of well-defined porphyrin-based architectures. A new stepwise and rational synthesis of functionalized trans-A2B2-porphyrins is reported in which for the first time donor–acceptor-substituted cyclopropane precursors (d–a cyclopropanes) are exploited. The three presented d–a cyclopropanes are readily accessible in a multi-gram scale and serve as aldehyde equivalents in the reaction with an excess of pyrrole to afford the corresponding dipyrromethanes (DPMs). The three DPMs were synthesized in yields of 60–74%. They are stable in purified form in the absence of light and air and were subsequently condensed with a wide range of aliphatic and aromatic aldehydes bearing electron-donating or electron-withdrawing substituents followed by oxidation to form the corresponding trans-A2B2-porphyrins. Fourteen functionalized porphyrins were synthesized in yields of 14–31%, indicating the broad scope of the synthetic procedure. The possibility to introduce key functional groups is emphasized, which enables subsequent modification of these porphyrins with moieties inducing biological activity. Modification of the tetrapyrroles may occur by addition to one of the porphyrin peripheral double bonds, the use of substituents of the aryl groups or via the methoxycarbonyl group at two of the meso-substituents. Three examples of porphyrins were converted into the corresponding 7,8-dihydroxychlorins by osmium-mediated dihydroxylation and one of the resulting chlorins was subjected to saponification to give a highly polar chlorin dicarboxylic acid. A 4-bromophenyl-substituted d–a cyclopropane was prepared by rhodium-catalyzed cyclopropanation and then transformed into a DPM which was subsequently condensed to a porphyrin. Its Zn complex allowed a Heck reaction to afford the functionalized bis(alkenyl)-substituted trans-A2B2-Zn-porphyrin.