Showing papers on "Cyclopropane published in 2016"
TL;DR: It is demonstrated that the developed catalytic system effectively promotes the asymmetric cyclopropanation of a wide variety of olefins to produce the desiredcyclopropane products in high yields with excellent stereocontrol.
Abstract: ConspectusThe transition-metal-catalyzed asymmetric cyclopropanation of olefins with diazoacetates has become one of the most important methods for the synthesis of optically active cyclopropane derivatives, which are key pharmaceutical building blocks and present in a large number of natural products. To date, significant progress has been made in this area of research, and efficient stereocontrolled synthetic approaches to cyclopropane derivatives have been developed using rhodium, ruthenium, copper, and cobalt catalysts. However, the vast majority of these strategies are limited to electron-rich olefins, such as styrene derivatives, due to the electrophilicity of the metal–carbene intermediates generated from the reaction of the metal with the diazo compound. Recently, the D2-symmetric Co(II)–phophyrin complexes developed by Zhang et al. were shown to be the most efficient catalysts for the asymmetric cyclopropanation of electron-deficient olefins. This catalytic system is mechanistically distinct from...
109 citations
TL;DR: A large array of structurally unique natural products with strained cyclopropane and/or cyclobutane motifs are covered and their structural features, distributions, biological activities, as well as biogenetic considerations are summarized.
Abstract: The strained cyclopropane and/or cyclobutane subunits occurred in many complex natural products including terpenoids, steroids and alkaloids. Natural products with cyclopropane and/or cyclobutane motifs not only furnished fascinating structures, but also exhibited versatile biological activities, such as cytotoxic, anti-HIV, antimicrobial, antiviral, and immunosuppressive effects. This review covered a large array of structurally unique natural products with strained cyclopropane and/or cyclobutane motifs and summarized their structural features, distributions, biological activities, as well as biogenetic considerations.
93 citations
TL;DR: The truncated globin of Bacillus subtilis is engineered for the synthesis of a cyclopropane precursor to the antithrombotic agent ticagrelor, enabling a single-step biocatalytic route to this pharmaceutical intermediate.
Abstract: Extending the scope of biocatalysis to important non-natural reactions such as olefin cyclopropanation will open new opportunities for replacing multistep chemical syntheses of pharmaceutical intermediates with efficient, clean, and highly selective enzyme-catalyzed processes. In this work, we engineered the truncated globin of Bacillus subtilis for the synthesis of a cyclopropane precursor to the antithrombotic agent ticagrelor. The engineered enzyme catalyzes the cyclopropanation of 3,4-difluorostyrene with ethyl diazoacetate on a preparative scale to give ethyl-(1R, 2R)-2-(3,4-difluorophenyl)-cyclopropanecarboxylate in 79% yield, with very high diastereoselectivity (>99% dr) and enantioselectivity (98% ee), enabling a single-step biocatalytic route to this pharmaceutical intermediate.
70 citations
TL;DR: A distinctive N-substituent controlled electrophilic N-transfer of oxaziridines with donor-acceptor cyclopropanes in the presence of MgI2 is reported.
66 citations
TL;DR: Dinuclear Ni complexes supported by naphthyridine-diimine (NDI) ligands catalyze the reductive cyclopropanation of alkenes with CH2 Cl2 as the methylene source, constituting an entry into catalytic carbene transformations from oxidized methylene precursors.
Abstract: Dinuclear Ni complexes supported by naphthyridine-diimine (NDI) ligands catalyze the reductive cyclopropanation of alkenes with CH2 Cl2 as the methylene source. The use of mild terminal reductants (Zn or Et2 Zn) confers significant functional-group tolerance, and the catalyst accommodates structurally and electronically diverse alkenes. Mononickel catalysts bearing related N chelates afford comparatively low cyclopropane yields (≤20 %). These results constitute an entry into catalytic carbene transformations from oxidized methylene precursors.
66 citations
57 citations
TL;DR: A catalytic [3 + 1]-annulation reaction between cyclopropane 1,1-diester and aromatic amine is developed based on the relay catalysis strategy and biologically important azetidines and tetrahydroquinolines can be prepared directly.
53 citations
TL;DR: The synthetic utility of optically enriched functionalized cyclopropane was demonstrated in the first total synthesis of (+)-hamavellone B, which establishes the absolute configuration of natural (+-hamaveLLone B.
46 citations
TL;DR: A convenient approach to γ-nitroesters that can be efficiently transformed to the substituted pyrrolidones, structural analogues of racetame family drugs (rolipram, phenylpiracetam, etc.) is developed.
Abstract: A conceptually new type of donor-acceptor cyclopropane reactivity towards nucleophiles has been disclosed. An essential characteristic of the process is an unusual nucleophilic attack on the C(3)-position of a cyclopropane, combined with typical small ring-opening by cleavage of the C(1)-C(2) bond between the acceptor and the donor. Based on this new reaction between cyclopropane-1,1-diesters and nitroalkanes, we developed a convenient approach to γ-nitroesters that can be efficiently transformed to the substituted pyrrolidones, structural analogues of racetame family drugs (rolipram, phenylpiracetam, etc.).
45 citations
TL;DR: An original and recyclable chiral bidentate aniline-sulfoxide-based directing group has been developed and an unprecedented palladacycle intermediate generated through C-H activation of the cyclopropane moiety has been isolated and fully characterized.
Abstract: An original and recyclable chiral bidentate aniline-sulfoxide-based directing group has been developed This auxiliary allows challenging stereoselective Pd-catalyzed direct functionalization of small cycloalkanes through C-aryl and C-alkyl bond formation Although moderate diastereoselectivities are observed, both optically pure enantiomers of the highly functionalized products can be obtained separately by simple silica gel chromatography and cleavage of the chiral auxiliary This strategy was further applied to the preparation of enantiomerically pure 1,2,3-trisubstituted cyclopropane carboxylic acid derivatives, with three stereogenic centers and bearing both alkyl and aromatic substituents These molecular scaffolds are not yet reported in the literature The synthetic utility of this approach is validated by the chiral auxiliary being readily cleaved and recovered posteriori to the C-H activation step, without deterioration of its optical purity Finally, an unprecedented palladacycle intermediate generated through C-H activation of the cyclopropane moiety has been isolated and fully characterized Initial DFT calculations shed additional light on the reactivity of this original intermediate
45 citations
TL;DR: An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization.
TL;DR: This robust protocol exhibits excellent generality, delivering a wide spectrum of cyclopropane α-amino acid esters bearing contiguous quaternary carbon centers in high yields and diastereoselectivities.
TL;DR: A Pd(OAc)2-catalyzed alkylation reaction of the tertiary carbon of chiral cyclopropane substrates with alkyl iodides and bromides via C(sp(3))-H activation has been developed, providing an elusive example of a C-Hactivation-mediatedAlkylation of tertiary Carbon to effectively construct a quaternary carbon center.
TL;DR: Comparison of reactants with various substitution groups showed that electron donation on the three-membered ring boosted the TOF of ring opening and the linear products formed with 100% selectivity for ring opening of all reactants catalyzed by the Rh NP.
Abstract: Understanding the C–C bond activation mechanism is essential for developing the selective production of hydrocarbons in the petroleum industry and for selective polymer decomposition. In this work, ring-opening reactions of cyclopropane derivatives under hydrogen catalyzed by metal nanoparticles (NPs) in the liquid phase were studied. 40-atom rhodium (Rh) NPs, encapsulated by dendrimer molecules and supported in mesoporous silica, catalyzed the ring opening of cyclopropylbenzene at room temperature under hydrogen in benzene, and the turnover frequency (TOF) was higher than other metals or the Rh homogeneous catalyst counterparts. Comparison of reactants with various substitution groups showed that electron donation on the three-membered ring boosted the TOF of ring opening. The linear products formed with 100% selectivity for ring opening of all reactants catalyzed by the Rh NP. Surface Rh(0) acted as the active site in the NP. The capping agent played an important role in the ring-opening reaction kineti...
TL;DR: 3 catalytic cycles working in concert to generate cis cyclopropanes in good yields and stereoselectivities!
Abstract: In the present paper we report our latest efforts in pushing the boundaries of synergistic catalysis. We propose the use of 3 different catalytic cycles working in concert for the formation of cis cyclopropane derivatives of benzoxazoles with excellent stereoselectivities. This is the proof of concept that synergistic catalysis could be successfully used in cascade reactions.
TL;DR: In this paper, a gold catalyzed cycloisomerization of easily available 1,5-enynes containing a cyclopropane ring has been developed, efficiently providing cyclobutane-fused 1,4-cyclohexadiene derivatives in moderate to excellent yields.
Abstract: A gold(I)-catalyzed cycloisomerization of easily available 1,5-enynes containing a cyclopropane ring has been developed, efficiently providing cyclobutane-fused 1,4-cyclohexadiene, tricyclic cyclobutene, biscyclopropane and 1,3-cyclohexadiene derivatives in moderate to excellent yields. When the phenyl group was not ortho substituted, 1,4-cyclohexadienes could be produced. With an ortho substituent, three different products could be selectively synthesized by control of the temperature and the used gold(I) catalyst. The 1,5-enyne substrate first undergoes a classical enyne cycloisomerization to form a tricyclic cyclobutene key intermediate, which undergoes subsequent transformation to produce the desired products. A plausible reaction mechanism was proposed according to deuterium labeling experiments and intermediate trapping experiments, as well as DFT calculations. In our current reaction, the ortho substituent on the phenyl group controls the reaction outcome and the ortho substituent effect was found to originate from steric and electronic factors.
TL;DR: The impressive progress recently devoted to the synthesis of fluorocyclopropanes especially using asymmetric methods is reported and some recent reported 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 scaffolds with potential interest for the synthesis of new bioactive compounds. In this review, we report the impressive progress recently devoted to the synthesis of fluorocyclopropanes especially using asymmetric methods and highlight some recent reported applications. 1 Introduction 2 Addition of Carbenes to Fluoroalkenes 3 Addition of Fluorocarbenes to Alkenes 4 Michael Initiated Ring Closure 5 Nucleophilic Fluorination 6 Applications to the Synthesis of Biorelevant Compounds 7 Conclusion
TL;DR: The mechanochemical activation of cis-gem-difluorocyclopropane (cis-gDFC) mechanophore in toluene was characterized with single-molecule force spectroscopy and two transitions are observed in the force vs extension curves.
Abstract: The mechanochemical activation of cis-gem-difluorocyclopropane (cis-gDFC) mechanophore in toluene was characterized with single-molecule force spectroscopy. Unlike previously reported behavior in methyl benzoate (MB), two transitions are observed in the force vs extension curves of cis-gDFC polymers in toluene. The first transition occurs at the same force of ∼1300 pN observed previously in MB, but a second transition is observed at forces of ∼1800 pN that reveal the partial formation of the trans-gDFC isomer. The behavior is attributed to competing reactions of the cis-gDFC at the 1300 pN plateau: addition of oxygen to a ring-opened diradicaloid intermediate, and isomerization of cis-gDFC to its trans isomer.
TL;DR: Rhodacyclopentanones derived from carbonylative C–C activation of cyclopropyl ureas can be “captured” by pendant nucleophiles prior to “collapse” to 1,3-diazepanes.
Abstract: Rhodacyclopentanones derived from carbonylative C–C activation of cyclopropyl ureas can be “captured” by pendant nucleophiles prior to “collapse” to 1,3-diazepanes. The choice of N-substituent on the cyclopropane unit controls the oxidation level of the product, such that C4–C5 unsaturated or saturated systems can be accessed selectively.
TL;DR: The enantio- and diastereoselective formation of indenes spirofused to highly substituted cyclopropanes is described and a new cinchona alkaloid derived ammonium salt facilitates high selectivity and excellent yields at low catalyst loadings.
TL;DR: Mechanistic investigation implies that this reaction takes place through a P(NMe2 )3 -mediated cyclopropanation followed by a base-catalyzedcyclopropane rearrangement, which represents an unprecedented [1+4] annulation mode involving Kukhtin-Ramirez adducts.
Abstract: An unusual formal [1+4] annulation of α-dicarbonyl compounds with 1,1-dicyano-1,3-dienes has been realized, leading to facile syntheses of cyclopentenimines and cyclopentenones in a unique manner. Mechanistic investigation implies that this reaction takes place through a P(NMe2 )3 -mediated cyclopropanation followed by a base-catalyzed cyclopropane rearrangement. It therefore represents an unprecedented [1+4] annulation mode involving Kukhtin-Ramirez adducts.
TL;DR: In this paper, a highly facile and efficient electrophilic bromolactonization of cyclopropylcarboxylic acids could be effected by a Lewis basic sulfide catalyst.
Abstract: A highly facile and efficient electrophilic bromolactonization of cyclopropylcarboxylic acids could be effected by a Lewis basic sulfide catalyst. Mechanistic studies performed revealed that the cyclopropane substrates could undergo radical bromination upon exposure to light, yielding a mixture of regioisomers. In stark contrast, the Lewis basic sulfide catalyst could promote the electrophilic bromolactonization and yield the Markovnikov product exclusively.
TL;DR: In this article, a gold catalyzed cycloisomerization of easily available 1,5-enynes containing a cyclopropane ring has been developed, efficiently providing cyclobutane-fused 1,4-cyclohexadiene derivatives in moderate to excellent yields.
Abstract: A gold(I)-catalyzed cycloisomerization of easily available 1,5-enynes containing a cyclopropane ring has been developed, efficiently providing cyclobutane-fused 1,4-cyclohexadiene, tricyclic cyclobutene, biscyclopropane and 1,3-cyclohexadiene derivatives in moderate to excellent yields. When the phenyl group was not ortho substituted, 1,4-cyclohexadienes could be produced. With an ortho substituent, three different products could be selectively synthesized by control of the temperature and the used gold(I) catalyst. The 1,5-enyne substrate first undergoes a classical enyne cycloisomerization to form a tricyclic cyclobutene key intermediate, which undergoes subsequent transformation to produce the desired products. A plausible reaction mechanism was proposed according to deuterium labeling experiments and intermediate trapping experiments, as well as DFT calculations. In our current reaction, the ortho substituent on the phenyl group controls the reaction outcome and the ortho substituent effect was found to originate from steric and electronic factors.
TL;DR: Free-radical carbocyanation ofcyclopropenes offers straightforward access to tetrasubstituted cyclopropanes in satisfying yields with moderate diastereoselectivity and leads to functionalized acyclic systems having an all-carbon quaternary stereocenter.
TL;DR: The conjugation of the aryl ring with C═C bond and π stacking are proposed for the stereoselectivity of cyclopropanation, and configuration inversion is observed with the desilylation process.
TL;DR: The total synthesis of lycopalhine A has been accomplished and features construction of the tricyclic system via cleavage of a cyclopropane ring and an ensuing intramolecular Michael addition.
TL;DR: In this paper, a zinc-catalyzed three-component coupling of 1,3-dicarbonylic compounds, 2-alkynals and alkenes is reported.
TL;DR: The highly diastereoselective intramolecular [3+2] annulation via the ring-opening of a cyclopropane diester derivative has been developed to construct a dihydroquinolinone scaffold and the amide-linking mode shows obviously beneficial effects on the ring -opening of cycloprostane.
TL;DR: The first enantioselective cyclopropanation of enals using benzyl chlorides as bifunctional (nucleophilic and electrophilic) reagents with moderate to excellent stereoselectivities is described.
Abstract: Herein, we describe the first enantioselective cyclopropanation of enals using benzyl chlorides as bifunctional (nucleophilic and electrophilic) reagents. The reaction is simply catalyzed by chiral secondary amines to afford the formyl cyclopropane derivatives in good yields with moderate to excellent stereoselectivities.
TL;DR: Diverse hexahydropyrrolo[3,2-c]quinolinones, as the tricyclic core of martinellines, were efficiently assembled in good to excellent yield with a good diastereomeric ratio.
Abstract: An intramolecular [3 + 2]-annulation of amide-linked donor–acceptor cyclopropane with in situ-generated imine is described As a result, diverse hexahydropyrrolo[3,2-c]quinolinones, as the tricyclic core of martinellines, were efficiently assembled in good to excellent yield (up to 93%) with a good diastereomeric ratio (up to 98:2)