Showing papers on "Cyclopropane published in 2019"
TL;DR: The computed relaxed force constants of donor-acceptor cyclopropanes proved to be a good indicator for the reactivity of the three-membered ring.
Abstract: The kinetics of (3+2) cycloaddition reactions of 18 different donor-acceptor cyclopropanes with the same aldehyde were studied by in situ NMR spectroscopy. Increasing the electron density of the donor residue accelerates the reaction by a factor of up to 50 compared to the standard system (donor group=phenyl), whereas electron-withdrawing substituents slow down the reaction by a factor up to 660. This behavior is in agreement with the Hammett substituent parameter σ. The obtained rate constants from the (3+2) cycloadditions correlate well with data from additionally studied (3+n) cycloadditions with a nitrone (n=3) and an isobenzofuran (n=4). A comparison of the kinetic data with the bond lengths in the cyclopropane (obtained by X-ray diffraction and computation), or the 1 H and 13 C NMR shifts, revealed no correlation. However, the computed relaxed force constants of donor-acceptor cyclopropanes proved to be a good indicator for the reactivity of the three-membered ring.
84 citations
TL;DR: A cytochrome P450 variant with 11 amino acid substitutions and a large deletion of the non-catalytic P450 reductase domain is evolved for highly efficient carbene transfer to indoles, pyrroles, and cyclic alkenes, showcasing the tunability of hemoproteins for highly selective functionalization of cyclic targets and the power of directed evolution to enhance the scope of new-to-nature enzyme catalysts.
Abstract: Transfers of carbene moieties to heterocycles or cyclic alkenes to obtain C(sp2)–H alkylation or cyclopropane products are valuable transformations for synthesis of pharmacophores and chemical buil...
79 citations
TL;DR: These obtained bromophenol derivatives (6-26) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms and acetylcholinesterase (AChE) enzymes with Ki values in the range of 7.8 ± 0.9-58.3
69 citations
TL;DR: A 1,3‐aminothiolation was realized by reacting 2‐substituted cyclopropane 1,1‐dicarboxylates with sulfonamides and N‐(arylthio)succinimides with electrophilic selenium source.
Abstract: A 1,3-aminothiolation was realized by reacting 2-substituted cyclopropane 1,1-dicarboxylates with sulfonamides and N-(arylthio)succinimides. Under Sn(OTf)2 catalysis the transformation proceeded smoothly to the corresponding ring-opened products bearing the sulfonamide in the 1-position next to the donor and the arylthio residue in the 3-position next to the acceptor. The procedure was extended to the corresponding selenium analogues by employing N-(phenylseleno)succinimides as an electrophilic selenium source.
49 citations
TL;DR: The results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons and their performance in the first unified asymmetric synthesis of functionalized cyclopropanes is demonstrated.
Abstract: Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. The redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect allowed the asymmetric cyclopropanation of various olefins, including unfunctionalized aliphatic alkenes, that enables the three-step total synthesis of (-)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons.
49 citations
TL;DR: An efficient catalytic method to synthesize functionalized α-vinyl aldehydes with highly E/Z stereoselectivity has been demonstrated in the presence of Rh(II) catalyst.
Abstract: An efficient RhII -catalyzed synthesis of functionalized α-vinyl aldehydes with high E/Z stereoselectivity was developed. The reaction mediates the cyclopropanation of enaminones with vinyl carbenoids that are generated from cyclopropenes in situ to give the aminocyclopropane intermediates. Selective C-C bond cleavage of the cyclopropane intermediates leads to formation of α-vinyl aldehyde derivatives with high E/Z selectivity. This method proceeds at room temperature under very mild reaction conditions and works with a broad substrate scope.
41 citations
TL;DR: This method was integrated with liquid chromatography (LC) for LC/UVPD-MS analysis of cyclopropyl glycerophospholipids in Escherichia coli and for analysis of MAs in Mycobacterium bovis and M. tuberculosis lipid extracts.
Abstract: Subtle structural features in bacterial lipids such as unsaturation elements can have vast biological implications. Cyclopropane rings have been correlated with tolerance to a number of adverse conditions in bacterial phospholipids. They have also been shown to play a major role in Mycobacterium tuberculosis ( M. tuberculosis or Mtb) pathogenesis as they occur in mycolic acids (MAs) in the mycobacterial cell. Traditional collisional activation methods allow elucidation of basic structural features of lipids but fail to reveal the presence and position of cyclopropane rings. Here, we employ 213 nm ultraviolet photodissociation mass spectrometry (UVPD-MS) for structural characterization of cyclopropane rings in bacterial phospholipids and MAs. Upon UVPD, dual cross-ring C-C cleavages on both sides of the cyclopropane ring are observed for cyclopropyl lipids, resulting in diagnostic pairs of fragment ions spaced 14 Da apart, thus enabling cyclopropane localization. These diagnostic pairs of ions corresponding to dual cross-ring cleavage are observed in both negative and positive ion modes and afford localization of multiple cyclopropane rings within a single lipid. This method was integrated with liquid chromatography (LC) for LC/UVPD-MS analysis of cyclopropyl glycerophospholipids in Escherichia coli ( E. coli) and for analysis of MAs in Mycobacterium bovis ( M. bovis) and M. tuberculosis lipid extracts.
39 citations
TL;DR: In this paper, the atomic-scale origin of the higher rate constant of type A isomerization (involving a direct alkyl transfer, without any change in the branching degree) than the one of type B isomerisation (involving non-classical carbonium ions such as protonated cyclopropane (PCP), inducing a change in branching degree), is unraveled.
36 citations
TL;DR: In this review, recent efforts in the development of oxidative radical ring-opening/cyclization of cyclopropane derivatives, including methylenecyclopropanes, Cyclopropyl olefins andcyclopropanols are described.
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.
33 citations
TL;DR: The syntheses of substituted all-cis-1,2,3-trifluorocyclopropanes are described for the first time and the inherent conformational rigidity and lowering of log P makes this motif attractive for exploration as a substituent for pharmaceuticals and agrochemical research.
29 citations
TL;DR: Monitoring the in situ chemical evolution of the ice combined with temperature programmed desorption studies and tunable single photon ionization coupled to a reflectron time-of-flight mass spectrometer confirmed the synthesis of methylacetylene, propene, and vinylacetylene.
Abstract: Pure methane (CH4) ices processed by energetic electrons under ultra-high vacuum conditions to simulate secondary electrons formed via galactic cosmic rays (GCRs) penetrating interstellar ice mantles have been shown to produce an array of complex hydrocarbons with the general formulae: CnH2n+2 (n = 4-8), CnH2n (n = 3-9), CnH2n-2 (n = 3-9), CnH2n-4 (n = 4-9), and CnH2n-6 (n = 6-7). By monitoring the in situ chemical evolution of the ice combined with temperature programmed desorption (TPD) studies and tunable single photon ionization coupled to a reflectron time-of-flight mass spectrometer, specific isomers of C3H4, C3H6, C4H4, and C4H6 were probed. These experiments confirmed the synthesis of methylacetylene (CH3CCH), propene (CH3CHCH2), cyclopropane (c-C3H6), vinylacetylene (CH2CHCCH), 1-butyne (HCCC2H5), 2-butyne (CH3CCCH3), 1,2-butadiene (H2CCCH(CH3)), and 1,3-butadiene (CH2CHCHCH2) with yields of 2.17 ± 0.95 × 10-4, 3.7 ± 1.5 × 10-3, 1.23 ± 0.77 × 10-4, 1.28 ± 0.65 × 10-4, 4.01 ± 1.98 × 10-5, 1.97 ± 0.98 × 10-4, 1.90 ± 0.84 × 10-5, and 1.41 ± 0.72 × 10-4 molecules eV-1, respectively. Mechanistic studies exploring the formation routes of methylacetylene, propene, and vinylacetylene were also conducted, and revealed the additional formation of the 1,2,3-butatriene isomer. Several of the above isomers, methylacetylene, propene, vinylacetylene, and 1,3-butadiene, have repeatedly been shown to be important precursors in the formation of polycyclic aromatic hydrocarbons (PAHs), but until now their interstellar synthesis has remained elusive.
TL;DR: The highly enantioselective version has been realized to afford enantioenriched ACPAs with up to all three cyclopropyl carbons as stererogenic centers in one operation, representing the first example of enantiOSElective multicomponentcyclopropane synthesis.
TL;DR: These studies provide the first examples of multicomponent cycloadditions that proceed through C-C bond activation of "simple" electron poor cyclopropanes.
Abstract: Rh-catalyzed carbonylative C-C bond activation of cyclopropylamides generates configurationally stable rhodacyclopentanones that engage tethered alkenes in (3+1+2) cycloadditions. These studies provide the first examples of multicomponent cycloadditions that proceed through C-C bond activation of "simple" electron poor cyclopropanes.
TL;DR: The concept of a chameleon activating group is considered in the context of donor-acceptor cyclopropane chemistry and the alteration of chemoselectivity of spiro[oxindole-1,3'-cyclopropane] ring opening with nucleophiles is reflected.
TL;DR: A gold-catalyzed cascade cyclization of O-tethered 1,7-enynes bearing a cyclopropane moiety has been reported in this communication, affording multi-substituted furans in moderate to good yields.
TL;DR: Ten cyclopropane fatty acid synthases are expressed from various organisms in the oleaginous yeast Yarrowia lipolytica, a model yeast for lipid metabolism and naturally capable of producing large amounts of lipids.
Abstract: Cyclopropane fatty acids, which can be simply converted to methylated fatty acids, are good unusual fatty acid candidates for long‐term resistance to oxidization and low‐temperature fluidity useful for oleochemistry and biofuels. Cyclopropane fatty acids are present in low amounts in plants or bacteria. In order to develop a process for large‐scale biolipid production, we expressed 10 cyclopropane fatty acid synthases from various organisms in the oleaginous yeast Yarrowia lipolytica, a model yeast for lipid metabolism and naturally capable of producing large amounts of lipids.
The Escherichia coli cyclopropane fatty acid synthase expression in Y. lipolytica allows the production of two classes of cyclopropane fatty acids, a C17:0 cyclopropanated form and a C19:0 cyclopropanated form, whereas others produce only the C17:0 form. Expression optimization and fed‐batch fermentation set‐up enable us to reach a specific productivity of 0.032 g·L−1·hr−1 with a genetically modified strain containing cyclopropane fatty acid up to 45% of the total lipid content corresponding to a titre of 2.3 ± 0.2 g/L and a yield of 56.2 ± 4.4 mg/g.
TL;DR: An efficient and practical approach for the synthesis of substituted benzannulated seven-membered O-heterocycles from cyclopropane derivatives is described and the representative products exhibited selective antifungal activity in vitro against the fungus Cryptococcus neoformans.
TL;DR: An unprecedented Pd-catalyzed intramolecular Heck cyclization has been investigated on halogenated diene scaffolds undergoing various mode of cyclization and termination leading to the formation of structurally differing fused cyclopenta(e)none and aromatic analogue as mentioned in this paper.
TL;DR: Experimental studies prove that the charge-transfer complex is responsible for the conversion of thioketone to ketone.
TL;DR: It was confirmed that complexes of dihydrogen and cyclopropane are linked through the A-H…σ interactions that may be classified as hydrogen bonds, and hydrogen bonds are formed for complexes with cyclopentane.
Abstract: ωB97XD/aug-cc-pVTZ calculations were performed for complexes of dihydrogen, cyclopropane, cyclobutane and cyclopentane, with simple proton donating species such as hydrogen fluoride, hydrogen chloride, water, hydrogen cyanide and acetylene. Numerous dependencies between geometrical, energetic and topological parameters of complexes considered were found, since various theoretical approaches were applied: Quantum Theory of 'Atoms in Molecules' (QTAIM), Natural Bond Orbital (NBO) method and energy decomposition analysis (EDA). It was confirmed that complexes of dihydrogen and cyclopropane are linked through the A-H…σ interactions that may be classified as hydrogen bonds. In the case of complexes of cyclobutane such hydrogen bonds are rather weak. Other type and also weak A-H…C hydrogen bonds are formed for complexes with cyclopentane.
TL;DR: An operationally simple protocol to affect an atom transfer radical addition of commercially available ICH2Bpin to terminal alkenes has been developed and is highly selective for the cyclopropanation of unactivated terminalAlkenes over non-terminal alkenses and electron deficient alkene.
Abstract: An operationally simple method to affect an atom-transfer radical addition of commercially available ICH2 Bpin to terminal alkenes has been developed. The intermediate iodide can be transformed in a one-pot process into the corresponding cyclopropane upon treatment with a fluoride source. This method is highly selective for the cyclopropanation of unactivated terminal alkenes over non-terminal alkenes and electron-deficient alkenes. Due to the mildness of the procedure, a wide range of functional groups such as esters, amides, alcohols, ketones, and vinylic cyclopropanes are well tolerated.
TL;DR: The reaction pathway was found to be a stepwise mechanism that proceeds through the formation of a metallacyclobutane intermediate and is the first example of a computational chemical analysis of enantioselective control in an intramolecular carbene-transfer reaction using C1 -symmetric catalysts.
TL;DR: Asymmetric Kulinkovich cyclopropanation of carboxylic compounds with prochiral alkenes is reported in this paper, where the process is mediated by ''titanium(IV) (4R,5R)-TADDOLate complexes and affords correspondingly (Z)- or (E)-cyclopropanols with up to 84-87% ee in the event of intra- or intermolecular olefin ligand exchange in intermediate titanacyclopropane [Titanium II]-alkene] species.
Abstract: Asymmetric Kulinkovich cyclopropanation of carboxylic esters with prochiral alkenes is reported. The process is mediated by titanium(IV) (4R,5R)-TADDOLate complexes and affords correspondingly (Z)- or (E)-cyclopropanols with up to 84–87% ee in the event of intra- or intermolecular olefin ligand exchange in intermediate titanacyclopropane [titanium(II)-alkene] species. Configuration of the olefin double bond is preserved in the cyclopropane products, pointing out on total retention of configuration at Ti–C bond in the cyclopropane forming step. The results have been interpreted in the framework of ate complex mechanism, suggesting formation of pentacoordinated titanium ate species as a prerequisite of high enantiocontrol.
TL;DR: The development of Cu-catalyzed addition of carbon nucleophiles to vinylidene cyclopropanes was reported and the results were reported to be consistent with those of previous studies.
Abstract: The development of Cu-catalyzed addition of carbon nucleophiles to vinylidene cyclopropanes was reported. The reactions with 1,1-bisborylmethane provided homopropargylic boronate products by forming a C–C bond at the terminal carbon atom of the allene moiety of vinylidene cyclopropanes. Alkynyl boronates are also suitable nucleophile precursors in reactions with vinylidene cyclopropanes, and skipped diynes were obtained in high yields. In addition, the Cu-enolate generated from the initial addition of nucleophilic copper species to vinylidene cyclopropanes can be intercepted by an external electrophile. As such, vinylidene cyclopropane serves as a linchpin to connect a nucleophile and an electrophile by forming two carbon–carbon bonds sequentially.
TL;DR: Visible-light-promoted hydroxysulfonylation of alkylidenecyclopropanes with conservation of the cyclopropyl ring has been developed in this article.
Abstract: Visible-light-promoted hydroxysulfonylation of the C–C double bond of alkylidenecyclopropanes (ACPs) with conservation of the cyclopropyl ring has been developed. The difunctionalization reaction exhibits a broad substrate scope with excellent functional group compatibility, affording a series of cyclopropane-containing β-hydroxysulfones and cyclopropyl styrenes in 34–91% yields under mild conditions. The preliminary mechanistic investigation indicates that this difunctionalization reaction includes a radical process via a sulfone radical.
TL;DR: In this paper, a variety of cyclopropane-and dihydrofuran-fused spirooxindoles containing vicinal quaternary carbon centers were produced in up to 90% yield with up to 20 dr.
Abstract: Protecting group-controlled annulations of tetra-substituted oxindole olefins and sulfur ylides have been achieved for the synthesis of multifunctional cyclopropane- and dihydrofuran-fused spirooxindoles. Under precise annulation regulation, a variety of cyclopropane- and dihydrofuran-fused spirooxindoles containing vicinal quaternary carbon centers were produced in up to 90% yield with up to 20 : 1 dr. This reaction demonstrates high regio-, chemo- and diastereoselectivity, broad functional group tolerance and gram-scale capacity.
TL;DR: In this article, the reactivity of insufficiently explored 1λ 6 -isothiazolidine-1,1,4-triones (so-called β-keto-γ-sultams) was investigated.
TL;DR: The catalytic asymmetric synthesis of mono-fluoro-, -chloro- and -bromomethyl-1,2-diaryl cyclopropane ester is described and the synthetic utility of the chiralcyclopropanes was also demonstrated.
Abstract: The catalytic asymmetric synthesis of mono-fluoro-, -chloro- and -bromomethyl-1,2-diaryl cyclopropane ester is described. The reaction, using Rh2((S)-BTPCP)4 as a catalyst, allowed the formation of the desired cyclopropanes in good to excellent yields (up to 99%) and excellent diastereoselectivities (up to >20 : 1) and with a high level of enantioselectivities (up to 98% ee). Finally, the synthetic utility of the chiral cyclopropanes was also demonstrated.