Showing papers on "Cyclopropane published in 2018"

Asymmetric [3+2] Photocycloadditions of Cyclopropanes with Alkenes or Alkynes through Visible-Light Excitation of Catalyst-Bound Substrates.

Abstract: The herein reported visible-light-activated catalytic asymmetric [3+2] photocycloadditions between cyclopropanes and alkenes or alkynes provide access to chiral cyclopentanes and cyclopentenes, respectively, in 63-99 % yields and with excellent enantioselectivities of up to >99 % ee. The reactions are catalyzed by a single bis-cyclometalated chiral-at-metal rhodium complex (2-8 mol %) which after coordination to the cyclopropane generates the visible-light-absorbing complex, lowers the reduction potential of the cyclopropane, and provides the asymmetric induction and overall stereocontrol. Enabled by a mild single-electron-transfer reduction of directly photoexcited catalyst/substrate complexes, the presented transformations expand the scope of catalytic asymmetric photocycloadditions to simple mono-acceptor-substituted cyclopropanes affording previously inaccessible chiral cyclopentane and cyclopentene derivatives.

Lewis Acid Triggered Vinylcyclopropane–Cyclopentene Rearrangement

Abstract: We report a mild Lewis acid induced isomerization of donor–acceptor cyclopropanes, containing an alkenyl moiety and diverse electron-withdrawing group(s) at the adjacent positions, into substituted cyclopentenes. We have found that 1,1,2-trisubstituted cyclopent-3-enes were exclusively obtained in yield of 51–99% when cyclopropanes with a 2-substituted alkenyl group as a donor underwent isomerization. For cyclopropanes bearing a trisubstituted alkenyl group either the corresponding cyclopent-3-enes or isomeric cyclopent-2-enes having two acceptor groups at the C(1) atom were formed, with the reaction selectivity being determined by the applied Lewis acid. We have shown that the reactivity of the donor–acceptor cyclopropane increases with the increase of the electron-donating character of (hetero)aromatic group attached to the alkenyl moiety. The synthetic utility of the developed methodology was also demonstrated through the synthesis of polysubstituted cyclopentane and piperidine derivatives.

Concise Synthesis of (−)-Cycloclavine and (−)-5-epi-Cycloclavine via Asymmetric C–C Activation

Abstract: To illustrate the synthetic significance of C–C activation methods, here we describe an efficient strategy for the enantioselective total syntheses of (−)-cycloclavine and (−)-5-epi-cycloclavine, which is enabled by an asymmetric Rh-catalyzed “cut-and-sew” transformation between benzocyclobutenones and olefins. Despite the compact structure of cycloclavine with five-fused rings, the total synthesis was accomplished in 10 steps with a 30% overall yield. Key features of the synthesis include (1) a Pd-catalyzed tandem C–N bond coupling/allylic alkylation sequence to construct the nitrogen-tethered benzocyclobutenone, (2) a highly enantioselective Rh-catalyzed carboacylation of alkenes to forge the indoline-fused tricyclic structure, and (3) a diastereoselective cyclopropanation for preparing the tetrasubstituted cyclopropane ring. Notably, an improved catalytic condition has been developed for the nitrogen-tethered cut-and-sew transformation, which uses a low catalyst loading and allows for a broad substrate...

What's in a name? ‘Coinage-metal’ non-covalent bonds and their definition

Abstract: Many complexes of the type B⋯MX, (where B is a Lewis base such as H2, N2, ethyne, ethene, cyclopropane, H2O, H2S, PH3, or NH3, M is a coinage-metal atom Cu, Ag or Au, and X is a halogen atom) have now been characterised in the gas phase through their rotational spectra. It is pointed out that, for a given B, such complexes have angular geometries that are isomorphous with those of their hydrogen- and halogen-bonded counterparts B⋯HX and B⋯XY, respectively. Since the MX are, like the B, HX and XY referred to, closed-shell molecules, the complexes B⋯MX also involve a non-covalent bond. Therefore, the name ‘coinage-metal’ bond is suggested for the non-covalent interaction in B⋯MX, by analogy with hydrogen and halogen bonds. A generalised definition that covers all non-covalent bonds is also presented.

Diastereodivergent asymmetric Michael-alkylation reactions using chiral N,N′-dioxide/metal complexes

Abstract: A diastereodivergent asymmetric Michael-alkylation reaction between 3-chloro-oxindoles and β,γ-unsaturated-α-ketoesters has been achieved using L-RaPr2 /Sc(OTf)3 and L-PrPr2 /Mg(OTf)2 metal complexes as catalysts. Both rel-(1R,2S,3R) and rel-(1S,2S,3R) chiral spiro cyclopropane oxindoles were constructed in good yields, diastereoselectivities and ee values. The diastereodivergent control may originate from different alkylation pathways after the Michael addition, with either intramolecular trapping of the aza-ortho-xylylene intermediate or direct SN2 substitution.

Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2-b]pyridazines

Abstract: In this report, a facile synthesis of tetrahydropyridazines via a Lewis acid catalyzed annulation reaction of cyclopropane carbaldehydes and aryl hydrazines has been demonstrated. Moreover, the generated tetrahydropyridazine further participated in a cycloaddition reaction with donor–acceptor cyclopropanes to furnish hexahydropyrrolo[1,2-b]pyridazines. We also performed these two steps in one pot in a consecutive manner. In addition, a monodecarboxylation reaction of hexahydropyrrolo[1,2-b]pyridazine was achieved with a good yield.

A radical S-adenosyl-L-methionine enzyme and a methyltransferase catalyze cyclopropane formation in natural product biosynthesis

Abstract: Cyclopropanation of unactivated olefinic bonds via addition of a reactive one-carbon species is well developed in synthetic chemistry, whereas natural cyclopropane biosynthesis employing this strategy is very limited. Here, we identify a two-component cyclopropanase system, composed of a HemN-like radical S-adenosyl-l-methionine (SAM) enzyme C10P and a methyltransferase C10Q, catalyzes chemically challenging cyclopropanation in the antitumor antibiotic CC-1065 biosynthesis. C10P uses its [4Fe-4S] cluster for reductive cleavage of the first SAM to yield a highly reactive 5′-deoxyadenosyl radical, which abstracts a hydrogen from the second SAM to produce a SAM methylene radical that adds to an sp2-hybridized carbon of substrate to form a SAM-substrate adduct. C10Q converts this adduct to CC-1065 via an intramolecular SN2 cyclization mechanism with elimination of S-adenosylhomocysteine. This cyclopropanation strategy not only expands the enzymatic reactions catalyzed by the radical SAM enzymes and methyltransferases, but also sheds light on previously unnoticed aspects of the versatile SAM-based biochemistry. The biosynthesis of the antitumour antibiotic CC-1065 includes formation of a cyclopropane. Here, the authors identify the two enzymes that work together to catalyze this reaction, a radical S-adenosyl-l-methionine enzyme and a methyltransferase, and propose a mechanism for the cyclopropanation.

Donor-acceptor cyclopropanes as ortho-quinone methide equivalents in formal (4 + 2)-cycloaddition to alkenes.

Abstract: A new type of donor–acceptor cyclopropane reactivity towards alkenes was revealed for 2-arylcyclopropane-1,1-diesters that contain an OH-group in the ortho-position of the aryl substituent. In this case, the initial cyclopropanes participate in formal (4 + 2)-cycloaddition as synthetic equivalents of ortho-quinone methides which are potential intermediates generated under mild conditions in the presence of a Lewis acid.

Synthesis and structure—activity relationships of cyclopropane-containing analogs of pharmacologically active compounds

Abstract: The review summarizes information on cyclopropane as an independent pharmacophore group and as a fragment for modification of pharmacological activity level of medicines used in practice. The advantages of a cyclopropane fragment over its bioisosteres are that, on the one hand, this fragment imposes conformational rigidity on the molecules of physiologically active compounds and, on the other hand, the replacement of acyclic terminal and “linker” groups with a cyclopropane fragment increases the metabolic stability of the target structures and extends the scope of their therapeutic action.

Use of Cyclopropane as C1 Synthetic Unit by Directed Retro-Cyclopropanation with Ethylene Release

Abstract: Cyclopropanation of alkenes is a well-established textbook reaction for the synthesis of cyclopropanes, where a “high-energy” carbene species is exploited to drive the reaction forward. However, little attention has been focused toward molecular transformations involving the reverse reaction, retro-cyclopropanation (RC). This is because of difficulties associated with both cleaving the two geminal C–C single bonds and exploiting the generated carbenes for further transformations in an efficient and selective manner. Here, we report that a molybdenum-based catalytic system overcomes the above challenges and effects the RC of cyclopropanes bearing a pyridyl group with the release of ethylene (alkene) and the subsequent intramolecular cyclization leading to pyrido[2,1-a]isoindoles. The reaction allows for the uncommon use of cyclopropanes as C1 synthetic units in contrast to most conventional reactions in which cyclopropanes are used as C3 synthetic units. We anticipate that this new strategy will pave the way for C1 cyclopropane chemistry.

Cyclopropanation of Benzene Rings by Oxidatively Generated α-Oxo Gold Carbene: One-Pot Access to Tetrahydropyranone-Fused Cycloheptatrienes from Propargyl Benzyl Ethers.

Abstract: Cyclopropanations of benzene rings by oxidatively generated α-oxo gold carbenes are for the first time demonstrated in a Buchner reaction, in which readily available propargyl benzyl ethers are converted in one-pot to tetrahydropyranone-fused cycloheptatrienes via sequential oxidative gold catalysis and base-promoted isomerization. Additional examples of arene cyclopropanations without fragmentation of the cyclopropane ring are also realized.

Adsorption and oxidation of propane and cyclopropane on IrO2(110).

Abstract: We investigated the adsorption and oxidation of n-propane and cyclopropane (C3H8 and c-C3H6) on the IrO2(110) surface using temperature programmed reaction spectroscopy (TPRS) and density functional theory (DFT) calculations. We find that the activation of both C3H8 and c-C3H6 is facile on IrO2(110) at low temperature, and that the dissociated alkanes oxidize during TPRS to produce CO, CO2 and H2O above ∼400 K. Propane conversion to propylene is negligible during TPRS for the conditions studied. Our results show that the maximum yield of alkane that oxidizes during TPRS is higher for c-C3H6 compared with C3H8 (∼0.30 vs. 0.18 monolayer) and that pre-hydrogenation of the surface suppresses c-C3H6 oxidation to a lesser extent than C3H8. Consistent with the experimental results, DFT predicts that C3H8 and c-C3H6 form σ-complexes on IrO2(110) and that C–H bond activation of the complexes as well as subsequent dehydrogenation are highly facile via H-transfer to Obr atoms (bridging O-atoms). Our calculations predict that propane conversion to gaseous propylene is kinetically disfavored on IrO2(110) because HObr recombination makes Obr atoms available to promote further dehydrogenation at lower temperatures than those needed for the adsorbed C3H6 intermediate to desorb as propylene. We also present evidence that that the ability for c-C3H6 to activate via ring-opening is responsible for cyclopropane attaining higher reaction yields during TPRS and exhibiting a weaker sensitivity to surface pre-hydrogenation compared with n-propane.

Stereospecific C–H activation as a key step for the asymmetric synthesis of various biologically active cyclopropanes

Abstract: A rapid and efficient synthesis of hoshinolactam, an enantiopure cyclopropane containing natural product, is described. This strategy is based on stereospecific C(sp3)–H activation via unprecedented olefination on the cyclopropane core. The use of a stereogenic and easily recyclable directing group (S)-2-(p-tolylsulfinyl)aniline (APS) which was originally developed by our group allows obtention of diastereomerically pure products in high yields. Optically pure cyclopropanes are subsequently converted into enantiomerically pure targeted natural products. Furthermore a closely related synthetic scenario is employed to build up precursors of grenadamide and cascarillic acid.

Cascade Cleavage of Three-Membered Rings in the Reaction of D-A Cyclopropanes with 4,5-Diazaspiro[2.4]hept-4-enes: A Route to Highly Functionalized Pyrazolines.

Abstract: A new cascade process for reactions of donor–acceptor cyclopropanes (DACs) with spiro[cyclopropanepyrazolines] in the presence of EtAlCl2 or Ga halides is reported. The action of a Lewis acid results in DAC activation and addition of the carbocationic intermediate to the azocyclopropane system of the pyrazoline with opening of the second three-membered ring and addition of a halide anion from the Lewis acid. A specific feature of this process is that one activated cyclopropane ring activates another one, and depending on the component ratio, the process can involve two DAC molecules and one pyrazoline molecule or one DAC molecule and two pyrazoline molecules. The process is tolerant to various functional groups and occurs with a wide range of substrates to give polyfunctionalized structures based on a 2-pyrazoline moiety.

Lewis Acid-Mediated Ring-Opening Reactions of trans-2-Aroyl-3-styrylcyclopropane-1,1-dicarboxylates: Access to Cyclopentenes and E,E-1,3-Dienes.

Abstract: The ring-opening reaction of trans-2-aroyl-3-styrylcyclopropane-1,1-dicarboxylates was investigated with different Lewis acids. With SnCl4, the cyclopropane dicarboxylates afforded cyclopentene derivatives through ring opening followed by cyclization (vinylcyclopropane–cyclopentene rearrangement). With TiCl4, they furnished E,E-1,3-diene derivatives stereoselectively via ring opening followed by proton elimination.

Highly diastereoselective synthesis of cyclopropane-fused spiro-pseudoindoxyl derivatives through [2 + 1] annulation of 2-ylideneoxindoles and sulfonium bromides.

Abstract: Compared with the intensively studied C3 spirooxindoles, limited reliable approaches are reported for synthesizing structurally analogous C2-spiropseudoindoxyl derivatives. Here, we developed an efficient method for highly diastereoselective synthesis of cyclopropane-fused spiropseudoindoxyl derivatives (up to 88% yield and >20 : 1 dr in all cases) through [2 + 1] annulation of (Z)-2-ylideneoxindoles with sulfur ylides.

3-Cyclopropyl-1,2-dimethyldiaziridine: synthesis and study of molecular structure by gas electron diffraction method

Abstract: The molecular structure and conformational behavior of 3-cyclopropyl-1,2-dimethyldiaziridine have been for the first time experimentally studied by gas-phase electron diffraction and quantum chemical calculations. The two most stable conformers at 298 K possess anti and gauche mutual ring orientation (with prevalence of the anti conformer) whereas only one anti conformer is observed in solution. The determined structural parameters of gaseous 3-cyclopropyl-1,2-dimethyldiaziridine have been compared with those for 3,3-bidiaziridine structural analogues in the crystal phase. The simple and convenient procedure for the synthesis of 3-cyclopropyl-1,2-dimethyldiaziridine comprising cyclopropane and diaziridine rings in one molecule was developed. The standard enthalpy of formation of 3-cyclopropyl-1,2-dimethyldiaziridine in the gas phase was calculated using Gaussian-4 theory, yielding value of 281.9 ± 5.0 kJ/mol.

Gold-Catalyzed Formal C-C Bond Insertion Reaction of 2-Aryl-2-diazoesters with 1,3-Diketones.

Abstract: The transition-metal-catalyzed formal C-C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3-diketones instead gives C-H bond insertion products. Herein, we report a protocol for a gold-catalyzed formal C-C bond insertion reaction of 2-aryl-2-diazoesters with 1,3-diketones, which provides efficient access to polycarbonyl compounds with an all-carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Bronsted acid to the reaction mixture improves the yield of the C-C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring-opening of the resulting donor-acceptor-type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis-acid-catalyzed C-C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.