Showing papers on "Cyclopropane published in 2012"
TL;DR: In this article, the acid-promoted intramolecular cycloadditions of activated cyclo-propanes were systematically described, and the potential of this strategy has been demonstrated by the synthesis of natural products.
Abstract: In this account we have systematically described the acid-promoted intramolecular cycloadditions of activated cyclopropanes, which were conceptually classified into intramolecular cross-cycloadditions (IMCC) and intramolecular parallel-cycloadditions. The IMCC provided a general and efficient strategy for construction of structurally complex and diverse bridged bicyclic skeletons. The potential of this strategy has been demonstrated by the synthesis of natural products. 1 Introduction 2 [3+2]IMCC of Cyclopropane 1,1-Diester with C=O 3 [3+2]IMCC of Cyclopropane 1,1-Diester with C=N 4 [3+2]IMCC of Cyclopropane 1,1-Diester with C=C 5 [3+3]IMCC of Cyclopropane 1,1-Diester with Nitrones 6 [3+2]IMCC of Mono-donor/Mono-acceptor Cyclopropane with C=O 7 Lewis Acid Regulated Domino Cycloisomerization/[4+2]IMCC or [3+2]IMCC of Alkynylcyclopropane Ketone with C=O and C=N 8 Conclusions and Outlook
117 citations
TL;DR: Analysis of the alkyne-insertion transition states revealed that the serious steric repulsion between the substituents in theAlkyne moiety of the substrates and the rigid H(8)-BINAP backbone is responsible for not generating the disfavored [3 + 2] cycloadducts.
Abstract: A highly enantioselective Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of 1-yne-VCPs to bicyclo[3.3.0] compounds with an all-carbon chiral quaternary stereocenter at the bridgehead carbon was developed. DFT calculations of the energy surface of the catalytic cycle (complexation, cyclopropane cleavage, alkyne insertion, and reductive elimination) of the asymmetric [3 + 2] cycloaddition reaction indicated that the rate- and stereo-determining step is the alkyne-insertion step. Analysis of the alkyne-insertion transition states revealed that the serious steric repulsion between the substituents in the alkyne moiety of the substrates and the rigid H(8)-BINAP backbone is responsible for not generating the disfavored [3 + 2] cycloadducts.
117 citations
TL;DR: Warming of 4-phthalimido-N-mesyl-1,2,3-triazole in the presence of alkenes followed by silica gel induced hydrolysis results in a highly diastereoselective and catalyst-free entry to N-phthalIMidocyclopropanecarboxaldehydes.
112 citations
TL;DR: Heavily substituted cyclopropane esters were prepared in high yields, complete diastereoselection and high enantioselectivity, and allowed multi-gram preparation of desired products.
85 citations
TL;DR: A series of quinoline and tetrahydroquinoline derivatives were prepared via a one-pot protocol involving intramolecular palladium(0)-catalyzed cyclopropane sp3 C-H bond functionalization and subsequent oxidation or reduction as mentioned in this paper.
Abstract: A series of quinoline and tetrahydroquinoline derivatives were prepared via a one-pot protocol involving intramolecular palladium(0)-catalyzed cyclopropane sp3 C–H bond functionalization and subsequent oxidation or reduction. The reaction conditions demonstrate good tolerance for a wide range of functional groups. Evidence suggests that the reaction proceeds through C–H bond cleavage and C–C bond formation to generate a dihydroquinoline intermediate via in situcyclopropane ring-opening.
85 citations
TL;DR: A cagelike bisoxazoline-derived Cu catalyst is designed and found it can promote the asymmetric cyclopropanation reaction of malonate-derived metallocarbenes with both terminal and multisubstituted olefins with high selectivity.
Abstract: Using phenyliodonium ylide malonate (I) the cyclopropanation of terminal (II) as well as di- and trisubstituted olefins proceeds highly enantioselectively.
84 citations
TL;DR: Cyclopropane hemimalonates, when treated with sodium azide, undergo a tandem ring-opening decarboxylation to produce γ-azidobutyric acids in good yields.
Abstract: Cyclopropane hemimalonates, when treated with sodium azide, undergo a tandem ring-opening decarboxylation to produce γ-azidobutyric acids in good yields. These adducts were hydrogenated to form γ-aminobutyric acid (GABA) methyl esters.
79 citations
TL;DR: A plausible mechanistic rationale and a catalytic cycle for these unusual ruthenium-catalyzed hydroarylation reactions have been proposed and the structures of the most important new products have been unambiguously determined by X-ray diffraction analyses.
Abstract: Intermolecular hydroarylation reactions of highly strained methylenecyclopropanes 2-phenylmethylenecyclopropane (1), 2,2-diphenylmethylenecyclopropane (2), methylenespiropentane (3), bicyclopropylidene (4), (dicyclopropylmethylene)cyclopropane (5), and benzhydrylidenecyclopropane (6) through C-H bond functionalization of 2-phenylpyridine (7 a) and other arenes with directing groups were studied. The reaction was very sensitive to the substitution on the methylenecyclopropanes. Although these transformations involved (cyclopropylcarbinyl)-metal intermediates, substrates 1 and 4 furnished anti-Markovnikov hydroarylation products with complete conservation of all cyclopropane rings in 11-93 % yield, whereas starting materials 3 and 5 were inert toward hydroarylation. Methylenecyclopropane 6 formed the products of formal hydroarylation reactions of the longest distal C-C bond in the methylenecyclopropane moiety in high yield, and hydrocarbon 2 afforded mixtures of hydroarylated products in low yields with a predominance of compounds that retained the cyclopropane unit. As byproducts, Diels-Alder cycloadducts and self-reorganization products were obtained in several cases from substrates 1-3 and 5. The structures of the most important new products have been unambiguously determined by X-ray diffraction analyses. On the basis of the results of hydroarylation experiments with isotopically labeled 7 a-[D(5)], a plausible mechanistic rationale and a catalytic cycle for these unusual ruthenium-catalyzed hydroarylation reactions have been proposed. Arene-tethered ruthenium-phosphane complex 53, either isolated from the reaction mixture or independently prepared, did not show any catalytic activity.
65 citations
TL;DR: F fused cyclopentane derivatives with multiple contiguous stereocenters can be synthesized with excellent diastereoselectivity through Cu(II)/bisoxazoline-catalyzed intermolecular cycloaddition reactions of cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers.
Abstract: Cyclopropane rings true: By selecting the appropriate substituents on the ester and silyl groups, fused cyclopentane derivatives with multiple contiguous stereocenters can be synthesized with excellent diastereoselectivity through Cu(II)/bisoxazoline-catalyzed intermolecular [3+2] cycloaddition reactions of cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers (see scheme).
64 citations
TL;DR: The different strategies to access monofluorocyclopropanes are reported and some of their attractive biological applications are highlighted.
Abstract: The combination of a fluorine atom and a cyclopropane ring, which both possess unique structural and chemical features, can generate new relevant building blocks for the discovery of efficient fluorinated biologically active agents. In this review, we report the different strategies to access monofluorocyclopropanes and highlight some of their attractive biological applications.
63 citations
TL;DR: In this article, the activation effect of Lewis acids on the cyclopropane ring has been shown experimentally and a single crystal of the complex with SnCl4 has been obtained, and an X-ray diffraction study has been performed.
TL;DR: Giving direction: An C sp 3-H bond activation directed by a rhodacycle intermediate has been found to occur in a Rh(I)-catalyzed reaction between an allene moiety having a tert-butyl substituent, and tethered alkynes.
Abstract: Giving direction: An C sp 3-H bond activation directed by a rhodacycle intermediate has been found to occur in a Rh(I)-catalyzed reaction between an allene moiety having a tert-butyl substituent, and tethered alkynes. Cyclic compounds containing a cyclopropane ring were obtained in good to high yields (up to 92%).
TL;DR: A derivatization study using 6 as a lead molecule led to the development of highly potent inhibitors in which the structure-activity relationship as well as the binding mode of the compounds clearly differ from those of known amidine-type inhibitors.
Abstract: Improvement of a drug’s binding activity using the conformational restriction approach with sp3 hybridized carbon is becoming a key strategy in drug discovery. We applied this approach to BACE1 inhibitors and designed four stereoisomeric cyclopropane compounds in which the ethylene linker of a known amidine-type inhibitor 2 was replaced with chiral cyclopropane rings. The synthesis and biologic evaluation of these compounds revealed that the cis-(1S,2R) isomer 6 exhibited the most potent BACE1 inhibitory activity among them. X-ray structure analysis of the complex of 6 and BACE1 revealed that its unique binding mode is due to the apparent CH−π interaction between the rigid cyclopropane ring and the Tyr71 side chain. A derivatization study using 6 as a lead molecule led to the development of highly potent inhibitors in which the structure–activity relationship as well as the binding mode of the compounds clearly differ from those of known amidine-type inhibitors.
TL;DR: The Ru(II)-Pheox complex is an efficient catalyst for the intermolecular cyclopropanation of various terminal olefins with succinimidyl diazoacetate in high yields with excellent diastereoselectivities and enantioselectivity.
TL;DR: The protocol was used as a key step in the total synthesis of the sponge-derived macrolide clavosolide A and can be used for the preparation of cyclopropane-substituted tetrahydropyrans.
TL;DR: The first example of potent non-natural small molecule inhibitors of HiOASS-A, a pyridoxal-5′-phosphate-dependent enzyme responsible for cysteine biosynthesis in many pathological microorganisms, is reported.
Abstract: O-Acetylserine sulfhydrylase (isoform A, OASS-A) is a pyridoxal-5′-phosphate-dependent enzyme responsible for cysteine biosynthesis in many pathological microorganisms. It is proposed that inhibition of OASS-A could represent a novel strategy to overcome bacterial resistance to antibiotics. A class of 2-substituted-cyclopropane-1-carboxylic acids was synthesized, based on structural determinants grasped by analyzing a group of synthetic pentapeptides known to efficiently bind OASS-A from Haemophilus influenzae (HiOASS-A). The cyclopropane derivatives were submitted to a binding affinity assay with HiOASS-A and three of them, with Kdiss in the low micromolar range, showed higher affinity than the most active synthetic pentapeptide. Thus, in this communication we report the first example of potent non-natural small molecule inhibitors of HiOASS-A. In addition, a molecular modelling study suggested a possible inhibition mechanism, through which the new cyclopropane ligands block HiOASS-A. Noteworthily, the novel, small-sized, non-peptidic inhibitors retain the structural motifs of the bulky peptides, which are relevant for the enzyme inhibition.
TL;DR: The mechanism of halonium-initiated tandem oxa-cyclization and ring opening of cyclopropane was proposed and a variety of nucleophiles were found to open the cycloprostane.
TL;DR: The cyclohexenone core of welwitindolinones was synthesized by a Rh(I)-catalyzed [5 + 1]-cycloaddition of an allenylcyclopropane with CO.
TL;DR: A FeCl(3) promoted [3 + 2] annulation of dimethyl 2-vinyl and arylcyclopropane-1,1-dicarboxylate with aryL isothiocyanates has been developed to give pyrrolidine-2-thiones in good yields with high regioselectivity.
Abstract: A FeCl3 promoted [3 + 2] annulation of dimethyl 2-vinyl and arylcyclopropane-1,1-dicarboxylate with aryl isothiocyanates has been developed to give pyrrolidine-2-thiones in good yields with high regioselectivity.
TL;DR: A new, highly stereoselective intramolecular cyclopropanation of vinylogous carbamates with carbenes in the presence of Cu(acac)(2) as the catalyst has been developed for the construction ofcyclopropapyrrolidinones.
Abstract: A new, highly stereoselective intramolecular cyclopropanation of vinylogous carbamates with carbenes in the presence of Cu(acac)2 as the catalyst has been developed for the construction of cyclopropapyrrolidinones. The ‘syn’ isomer of N-DAC can be converted to the ‘anti’ isomer by simple silica gel treatment. Regioselective cleavage of each of the cyclopropane bonds of these two acceptor substituted N-DACs led to a diverse array of azacycles.
TL;DR: 1,1-Cyclopropane aminoketones were efficiently synthesized in high yields by the tandem reaction of α-amino aryl ketones with vinyl sulfonium salts using DBU as the base in CH(2)Cl(2).
TL;DR: The role of zeolite topology in the stepwise methylation of ethene by surface methoxides was investigated in this paper, where density functional theory was employed in the determination of reaction mechanisms and energy barriers.
Abstract: The role of zeolite topology in the stepwise methylation of ethene by surface methoxides was investigated. Density functional theory was employed in the determination of reaction mechanisms and energy barriers. Elementary steps were studied across multiple frameworks (i.e., BEA, CHA, FER, MFI, and MOR) constituting a wide variety of confinement environments. Surface methoxides were found to react with ethene through a transition state containing planar CH3 species, which was best stabilized at the intersection of the 10-membered ring channels of MFI. A cyclopropane reaction intermediate was found in all cases; its decomposition necessitated a transition state containing a primary carbocation, which was best stabilized within the 8-membered ring side pockets of MOR. The activation energies corresponding to each transition state geometry depend upon different aspects of the local pore topology, implying that confinement effects can not be simply correlated to pore size.
TL;DR: In this paper, a Cu(I)-catalyzed asymmetric cyclopropanation of alkenes with an iodonium ylide has been developed and conditions were developed to convert the trans products to the cis isomers.
TL;DR: An efficient method to construct cyclopenta[c]chromene skeletons by Lewis acid-catalyzed intramolecular [3+2] cycloaddition of cyclopropane 1,1-diesters with alkynes is presented.
Abstract: An efficient method to construct cyclopenta[c]chromene skeletons by Lewis acid-catalyzed intramolecular [3+2] cycloaddition of cyclopropane 1,1-diesters with alkynes is presented. Two new fused cycles can be formed in one step in moderate to excellent yields (up to 94 %), and the products can be converted into bioactive barbituric acid derivatives (1) under simple reaction conditions.
TL;DR: In this paper, a clickable polymers with a very high local density of allyl side groups was developed by the anionic ring-opening polymerization of diallyl cyclopropane-1,1-dicarboxylate using as an initiating system a protic precursor whose acid-base reaction with the t -BuP 4 phosphazene base generated the initiator in situ.
TL;DR: In this article, the trifluoromethylated cyclopropane derivatives in excellent yields were obtained by double alkylation with active methylene compounds in dimethyl sulfoxide or ethyl acetate.
Abstract: ( E )-Diphenyl-β-(trifluoromethyl)vinylsulfonium triflate, readily prepared from 2-bromo-3,3,3-trifluoroprop-1-ene in two steps, undergoes double alkylation with active methylene compounds in dimethyl sulfoxide or ethyl acetate, in an open vessel at room temperature, to provide the corresponding trifluoromethylated cyclopropane derivatives in excellent yields. The cyclopropane, ethyl 1-cyano-2-(trifluoromethyl)cyclopropanecarboxylate is subjected to a ring-opening reaction followed by cyclization to afford a trifluoromethylated dihydroaminothiophene, which on oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone furnishes the corresponding trifluoromethylated aminothiophene in a high 88% yield.
TL;DR: 3JHH couplings of the epoxy ring proton with side‐chain protons were obtained and shown to be dependent on both the H―C ―C―H and H―O―C―O orientations.
Abstract: The 1H chemical shifts of selected three-membered ring compounds in CDCl3 solvent were obtained. This allowed the determination of the substituent chemical shifts of the substituents in the three-membered rings and the long-range effect of these rings on the distant protons. The substituent chemical shifts of common substituents in the cyclopropane ring differ considerably from the same substituents in acyclic fragments and in cyclohexane and were modelled in terms of a three-bond (γ)-effect. For long-range protons (more than three bonds removed), the substituent effects of the cyclopropane ring were analysed in terms of the cyclopropane magnetic anisotropy and steric effect. The cyclopropane magnetic anisotropy (ring current) shift was modelled by (a) a single equivalent dipole perpendicular to and at the centre of the cyclopropane ring and (b) by three identical equivalent dipoles perpendicular to the ring placed at each carbon atom. Model (b) gave a more accurate description of the 1H chemical shifts and was the selected model. After parameterization, the overall root mean square error for the dataset of 289 entries was 0.068 ppm. The anisotropic effects are significant for the cyclopropane protons (ca 1 ppm) but decrease rapidly with distance. The heterocyclic rings of oxirane, thiirane and aziridine do not possess a ring current. 3JHH couplings of the epoxy ring proton with side-chain protons were obtained and shown to be dependent on both the H―C―C―H and H―C―C―O orientations. Both density functional theory calculations and a simple Karplus-type equation gave general agreement with the observed couplings (root mean square error 0.5 Hz over a 10-Hz range). Copyright © 2012 John Wiley & Sons, Ltd.
TL;DR: The structure of the phorbol-binding domain (C1B) of PKCδ complexed with an ether and with an alcohol at 1.36-Å resolution is solved and both van der Waals interactions and hydrogen-bonding are essential for binding to occur.