Gold(I)‐Catalyzed Divergence in the Preparation of Bicyclic Enol Esters: From Exclusively [3C+2C]‐Cycloaddition Reactions to Exclusive Formation of Vinylcyclopropanes

With the use of benzonitrile‐stabilized Au^I catalyst [Au(IPr)(NCPh)]SbF₆ ( Ic ; IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene), a spectrum of reactivity is observed for propargyl ester 4 a with cyclic vinyl ethers, ranging from exclusively [3C+2C] cycloaddition reactions to exclusively cyclopropanation depending only on the structure of the substrate. Some initially formed cyclopropanation products rearrange into the corresponding formally [3C+2C] cycloaddition products after treatment with fresh Au^I complex at 80 °C. Vinylcyclopropanes formed from dihydrofuran and dihydropyran resisted such rearrangement, even in the presence of fresh Au^I catalyst at elevated temperature. This study addresses an important mechanistic question concerning whether the five‐membered‐ring products were produced by a direct [3C+2C] cycloaddition reaction or by a sequential cyclopropanation/ring‐expansion reaction. A dual pathway is proposed for the Au^I‐catalyzed reactions between propargyl esters and cyclic vinyl ethers. The different behavior among vinyl cyclic ethers is attributed to the difference in the polarization of the π bond. Highly polarized bonds appear to undergo the cycloaddition reaction whereas less polar π‐bonds produce cyclopropanes.     

Formal and standard ruthenium-catalyzed [2 + 2 + 2] cycloaddition reaction of 1,6-diynes to alkenes: a mechanistic density functional study

"Formal" and standard Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,6-diynes 1 to alkenes gave bicyclic 1,3-cyclohexadienes in relatively good yields. The neutral Ru(II) catalyst was formed in situ by mixing equimolecular amounts of [Cp*Ru(CH3CN)3]PF6 and Et4NCl. Two isomeric bicyclic 1,3-cyclohexadienes 3 and 8 were obtained depending on the cyclic or acyclic nature of the alkene partner. Mechanistic studies on the Ru catalytic cycle revealed a clue for this difference: (a) when acyclic alkenes were used, linear coupling of 1,6-diynes with alkenes was observed giving 1,3,5-trienes 6 as the only initial reaction products, which after a thermal disrotatory 6e-pi electrocyclization led to the final 1,3-cyclohexadienes 3 as probed by NMR studies. This cascade process behaved as a formal Ru-catalyzed [2 + 2 + 2] cycloaddition. (b) With cyclic alkenes, the standard Ru-catalyzed [2 + 2 + 2] cycloaddition occurred, giving the bicyclic 1,3-cyclohexadienes 8 as reaction products. A complete catalytic cycle for the formal and standard Ru-catalyzed [2 + 2 + 2] cycloaddition of acetylene and cyclic and acyclic alkenes with the Cp*RuCl fragment has been proposed and discussed based on DFT/B3LYP calculations. The most likely mechanism for these processes would involve the formation of ruthenacycloheptadiene intermediates XXIII or XXVII depending on the alkene nature. From these complexes, two alternatives could be envisioned: (a) a reductive elimination in the case of cyclic alkenes 7 and (b) a beta-elimination followed by reductive elimination to give 1,3,5-hexatrienes 6 in the case of acyclic alkenes. Final 6e-pi electrocyclization of 6 gave 1,3-cyclohexadienes 3.     

CpRuCl(PPh3)2-catalyzed cyclopropanation of bicyclic alkenes with tertiary propargylic acetates

The electron-rich cyclopentadienylruthenium complex CpRuCl(PPh3)2 turns out to be an efficient catalyst for the regio- and stereoselective cyclopropanation of bicyclic alkenes with tertiary propargylic carboxylates. The reaction provides 1,2,3-trisubstituted cyclopropanes in high yields as a single stereoisomer instead of the expected cyclobutenes via [2 + 2] cycloaddition. Functional groups such as ethers, esters, alcohols, phenols, ketones, esters, carboxylic anhydrides, nitriles, halides, sulfones, imides, carbamates, and azines are tolerated with the catalyzed reaction. An efficient cyclopropanation of cyclobutenes was also demonstrated, providing the strained bicyclo[2.1.0(1,3)]pentane framework.     

Catalytic cyclopropanation of alkenes via (2-furyl)carbene complexes from 1-benzoyl-cis-1-buten-3-yne with transition metal compounds

The reaction of alkenes with conjugated ene-yne-ketones, such as 1-benzoyl-2-ethynylcycloalkenes, with a catalytic amount of Cr(CO)(5)(THF) gave 5-phenyl-2-furylcyclopropane derivatives in good yields. The key intermediate of this cyclopropanation is a (2-furyl)carbene complex generated by a nucleophilic attack of carbonyl oxygen to an internal alkyne carbon in pi-alkyne complex or sigma-vinyl cationic complex. A wide range of late transition metal compounds, such as [RuCl(2)(CO)(3)](2), [RhCl(cod)](2), [Rh(OAc)(2)](2), PdCl(2), and PtCl(2), also catalyzes the cyclopropanation of alkenes with ene-yne-ketones effectively. When the reactions were carried out with dienes as a carbene acceptor, the more substituted or more electron-rich alkene moiety was selectively cyclopropanated with the (2-furyl)carbenoid intermediate.     

A novel catalytic and highly enantioselective approach for the synthesis of optically active carbohydrate derivatives

A catalytic enantioselective inverse-electron demand hetero-Diels-Alder reaction of alpha,beta-unsaturated carbonyl compounds with electron-rich alkenes catalyzed by chiral bisoxazolines in combination with Cu(OTf)2 as the Lewis acid is presented. The reaction of gamma-substituted beta,gamma-unsaturated alpha-keto esters with vinyl ethers and various types of cis-disubstituted alkenes proceeds in good yield, high diastereoselectivity, and excellent enantioselectivity. The potential of the reaction is demonstrated by the synthesis of optically active carbohydrates such as spiro-carbohydrates, an ethyl beta-D-mannoside tetraacetate, and acetal-protected C-2-branched carbohydrates. On the basis of X-ray crystallographic data and the absolute configuration of the products, it is proposed that the alkene approaches the si-face of the reacting alpha,beta-unsaturated carbonyl functionality when coordinated to the catalyst.     

Click chemistry by microcontact printing on self-assembled monolayers: a structure-reactivity study by fluorescence microscopy

Microcontact printing (μCP) has developed into a powerful tool to functionalize surfaces with patterned molecular monolayers. μCP can also be used to induce a chemical reaction between a molecular ink and a self-assembled monolayer (SAM) in the nanoscale confinement between stamp and substrate. In this paper, we investigate the Huisgen 1,3-dipolar cycloaddition, the Diels-Alder cycloaddition and the thiol-ene/yne reaction induced by μCP. A range of fluorescent alkyne inks were printed on azide SAMs and fluorescence microscopy was used to monitor the extent of the 1,3-dipolar cycloaddition on a glass substrate. The rate of cycloaddition depends on the reactivity of the alkyne and on the presence of Cu(I). The cycloaddition is accelerated by Cu(I) but it also proceeds readily in the absence of Cu(I). In addition, a range of fluorescent diene inks were printed on alkene SAMs on glass. In this case, fluorescence microscopy was used to monitor the rate of the Diels-Alder cycloaddition as well as its retro-reaction. Finally, fluorescent thiol inks were printed on alkene SAMs on glass, and fluorescent alkenes and alkynes were printed on thiol SAMs. It is shown that reactions by μCP follow structure-reactivity relationships similar to solution reactions. Under optimized conditions all reactions lead to dense microarrays of addition products within minutes of printing time.     

Rates and mechanism of alkyne ozonation

The rates and products of the reactions of ozone with acetylene, methylacetylene, dimethylacetylene, and ethylacetylene have been studied in a long-path infrared cell at 21 ± 1°C. The gas phase reaction gives products formed by cleavage of the carbon–carbon triple bond. A mechanism is proposed that involves formation of a short-lived acid anhydride intermediate, which is energized by virtue of the reaction exothermicity and undergoes unimolecular decomposition. Formation of an α-dicarbonyl was observed in every case, but there is evidence that a side reaction on the walls accounted for that product. The general relationship between alkyne and alkene ozonation is discussed. The rate measurements showed that, unlike the alkenes, the rate of alkyne ozonation is not greatly affected by substitution with simple alkyl groups. The rate constant for C₂H₂ agrees with earlier work and thus provides additional support for the previously derived high A-factor for acetylene ozonation relative to alkenes.     

Synthesis of (−)‐Hebelophyllene E: An Entry to Geminal Dimethyl‐Cyclobutanes by [2+2] Cycloaddition of Alkenes and Allenoates

The first synthesis of hebelophyllene E is presented, along with assignment of its previously unknown relative configuration through synthesis of epi‐ent‐hebelophyllene E. Development of a catalytic enantioselective [2+2] cycloaddition of alkenes and allenoates provides access to the required chiral geminal dimethylcyclobutanes. Key to its success is the identification of a novel oxazaborolidine catalyst which promotes the cycloaddition in high enantioselectivities with good functional‐group tolerance (9 examples, up to 97:3 e.r.). Thus, a late‐stage cycloaddition using a fully functionalized alkene, followed by a diastereoselective reduction allows a concise entry to this class of natural products.     

Addition of Dialkyl Hydrogen Phosphites to Alkenes in the Presence of Carbonyl Complexes of Chromium Subgroup Metals and Iron

Depending on the reactant ratio and order of their mixing, reactions of dialkyl hydrogen phosphite with alkenes in the presence of catalytic amounts of homoligand carbonyl complexes of iron or chromium subgroup metals yield phosphonates by two pathways: reaction of dialkyl hydrogen phosphite with -coordinated alkene and addition to alkene of the product of reaction of dialkyl hydrogen phosphite with the transition metal carbonyl. The products of reactions of Fe(CO)₅ and W(CO)₆ with dialkyl hydrogen phosphites contain the phosphorus-metal bond.     

Ruthenium-catalyzed formal [4 + 2] cycloaddition of alkynes with alkenes: formation of cyclohexenedicarboxylates via isomerization of alkynes and successive Diels-Alder reaction

Formal [4 + 2] cycloaddition of alkynes with electron-deficient alkenes, which affords 3,6-dialkyl-4-cyclohexene-1,2-dicarboxylates, was achieved using Ru(η⁶-1,3,5-cyclooctatriene)(η²-dimethyl fumarate)₂ as a catalyst. The reaction mechanism consists of two steps, isomerization of an alkyne to conjugated dienes and successive Diels-Alder reaction of the generated dienes with an electron-deficient alkene.     

Synthesis of trans‐Disubstituted Alkenes by Cobalt‐Catalyzed Reductive Coupling of Terminal Alkynes with Activated Alkenes

A cobalt‐catalyzed reductive coupling of terminal alkynes, RC?CH, with activated alkenes, R′CH?CH₂, in the presence of zinc and water to give functionalized trans‐disubstituted alkenes, RCH?CHCH₂CH₂R′, is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl₂/P(OMe)₃/Zn catalyst system to afford 1,2‐trans‐disubstituted alkenes with high regio‐ and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl₂/P(OPh)₃/Zn system providing a mixture of 1,2‐trans‐ and 1,1‐disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3‐enynes and acetylene gas with alkenes. Furthermore, a phosphine‐free cobalt‐catalyzed reductive coupling of terminal alkynes with enones, affording 1,2‐trans‐disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air‐stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed.     

Information on the location of carbon-carbon double bonds in C6−C23 linear alkenes from carbon addition reactions in a quadrupole ion trap equipped with a pulsed sample-inlet system

Ion-molecule reactions of a number of alkene molecular ions with different neutral alkenes were studied in a quadrupole ion trap equipped with a pulsed sample-inlet system. The molecules studied include several isomeric unbranched hexenes, heptenes, octenes, and nonenes, as well as representative alkenes with ten, twelve, fourteen, and twenty-three carbon atoms. Transfer of structurally characteristic number of methylene units between the ionic and neutral reactants dominates the product distributions for all the alkenes studied, with the exception of 1-alkenes. Isomeric alkenes can be readily distinguished on the basis of their products from reactions with neutral alkenes. It is suggested that distonic intermediates are generated in these reactions, and that they fragment by alkene elimination after 1,2- and 1,5-hydride shifts. The ability to vary the reaction time, pressure of the neutral reagents, and the type of ions and neutral molecules present in the reaction chamber during each stage of the experiment sequence makes it possible to maximize the amount of structural information obtained for alkenes in these experiments. Use of CS ₂ ^+? to generate the alkene molecular ion by charge exchange yields the same information without the need to carry out a mass-selection step for the ionized alkene.     

Palladium-catalyzed cross-coupling reactions in one-pot multicatalytic processes

Palladium-catalyzed cross-coupling reactions have been investigated in multicatalytic processes to synthesize disubstituted alkenes and alkanes from carbonyl derivatives. The use of copper-catalyzed methylenation reactions is the key starting reaction to produce terminal alkenes which are not isolated, but submitted to further structure elongation. Not only is the isolation of the alkene intermediate unnecessary, but also the copper catalyst is a beneficial cocatalyst in the palladium-catalyzed cross-coupling reactions. The desired products are thus typically obtained in higher yields using this one-pot approach. We have used these processes to synthesize hydroxylated (E)-stilbenoids, which are known chemopreventive and chemotherapeutic agents, odorant-substituted indanes, and non-natural amino acids, such as homophenylalanine.     

Photosensitized intramolecular cyclization of furan and non-activated alkene: pathway switching by the substituent on the furan ring

A photosensitized reaction of furan with a non-activated simple alkene was investigated. Intramolecular Diels-Alder-type cycloaddition reactions between furan and a trisubstituted alkene were found to proceed in high yield in the presence of 9,10-dicyanoanthracene under UV irradiation to afford oxabicyclo[2.2.1]heptane derivatives in high stereoselectivity when the furan was alkyl substituted. On the other hand, the aryl-substituted furan cyclized via a completely different pathway to give spirocyclic and tricyclic products.     

Hypervalent iodine(III) reagents as safe alternatives to alpha-nitro-alpha-diazocarbonyls

A cyclopropanation reaction involving iodonium ylides generated in situ allows for efficient preparation of substituted 1-nitro-1-carbonyl cyclopropanes. This robust cyclopropanation reaction can be performed in organic solvents, biphasic aqueous media, or under solvent-free conditions with alkene substrates. The iodonium ylides generated in situ display some surprising differences in reactivity when compared to alpha-nitro-alpha-diazocarbonyl compounds. They do not undergo O-H insertion reactions and exhibit reduced reactivity with certain alkenes. [reaction: see text]     

Direct C−C Double Bond Cleavage of Alkenes Enabled by Highly Dispersed Cobalt Catalyst and Hydroxylamine

The utilization of a single-atom catalyst to break C−C bonds merges the merits of homogeneous and heterogeneous catalysis and presents an intriguing pathway for obtaining high-value-added products. Herein, a mild, selective, and sustainable oxidative cleavage of alkene to form oxime ether or nitrile was achieved by using atomically dispersed cobalt catalyst and hydroxylamine. Diversified substrate patterns, including symmetrical and unsymmetrical alkenes, di- and tri-substituted alkenes, and late-stage functionalization of complex alkenes were demonstrated. The reaction was successfully scaled up and demonstrated good performance in recycling experiments. The hot filtration test, catalyst poisoning and radical scavenger experiment, time kinetics, and studies on the reaction intermediate collectively pointed to a radical mechanism with cobalt/acid/O₂ promoted C−C bond cleavage as the key step.     

Radical additions of xenon difluoride to cis- and trans-1-phenylpropenes: comparison with trichloramine and iodobenzene dichloride

We would like to report data which support a free radical pathway for reaction of xenon difluoride (XeF₂) with alkenes in organic solvent. Radical intermediates have been proposed for reaction of XeF₂ to double bonds. For example, a radical pathway was suggested for the gas phase reaction of XeF₂ to ethylene and propene [1]. Zupan speculated on a radical cation pathway for the acid catalyzed reaction of XeF₂ with alkenes but gave no experimental evidence for this mechanism [2,3]. Radical cation intermediates were demonstrated for the reaction of XeF₂ to aromatics by Filler [4]. Acid catalyzed ionic reactions to unsaturated hydrocarbons have been reviewed [5].Zupan and Pollak have shown that alkenes do not react in aprotic solvent with XeF₂ at low concentrations of alkene unless acid catalyst is present [3]. However, we observed that illumination of a dilute solution of $\text{cis-}$ or $\text{trans}$-1-phenylpropenes (I) or (II) in methylene chloride at 0° with a 270 watt sunlamp produced IIIa and IIIb in less then two hours (Table). Furthermore, at high concentration of (I) and (II), a spontaneous reaction occurred in the dark between XeF₂ and these styrenes. The reaction conditions for both of these reactions imply a radical mechanism — the latter a molecule-induced pathway.     

A density functional theory study of the chemoselectivity and regioselectivity of the domino cycloaddition reactions of nitroalkenes with substituted alkenes

The chemoselectivity and regioselectivity of the domino intermolecular [4 + 2]/[3 + 2] cycloaddition reactions of nitroalkenes with substituted alkenes, vinyl ethers as electron-rich alkenes and vinyl ketones as electron-poor alkenes, have been studied using density functional theory (DFT) methods with the B3LYP functional and the 6-31G^* basis set. These domino processes comprise two consecutive cycloaddition reactions: the first one is an intermolecular [4 + 2] cycloaddition of the vinyl ether to the nitroalkene to give a nitronate intermediate, which then affords the final nitroso acetal adduct through an intermolecular [3 + 2] cycloaddition reaction with the vinyl ketone. The two consecutive cycloadditions present total chemoselectivity and ortho regioselectivity. While first [4 + 2] cycloaddition reaction takes place along the attack of the electron-rich alkene to nitroalkene, the [3 + 2] one takes place along the attack of the electron-poor alkene to the corresponding nitronate intermediate. This DFT study is in complete agreement with the experimental results. Received: 16 September 1999 / Accepted: 3 February 2000 / Published online: 2 May 2000     

First Cp*Co(III)-catalyzed Mizoroki-Heck coupling reactions of alkenes and aryl bromide/iodide

A Cp*Co(CO)I₂ catalyzed Mizoroki-Heck coupling of alkenes and aryl halide is established at feasible reaction conditions. The Cp*Co(III) catalyst excellently work to couple the aryl iodide and alkene, and produce up to 94% yield of the coupling product. In case of the coupling of aryl bromide and alkene, slightly reduced activity of the catalyst was observed, and moderate to good yield of the product was obtained. Apart from functionally different styrene, the catalyst was also able to activate the acrylates, which seems difficult to be activated by other reported metal complexes. The coupling proposed herein is tolerant a wide variety of aryl halides, stryenes, and acrylates enable to form CC bond using inexpensive metal in catalysis. Hence, the present catalyst is highly economical, consists a non-endangered metal and is highly efficient for Heck coupling reaction. Moreover, the cobalt metal in high oxidation state (+3) is not much explored for the CC cross-coupling reactions.     

Iridium complex-catalyzed [2+2+2] cycloaddition of alpha,omega-diynes with monoynes and monoenes

[reaction: see text] [Ir(cod)Cl]2/DPPE was found to be a new catalyst for the cycloaddition of alpha,omega-diynes with monoynes to give polysubstituted benzene derivatives in high yields. Internal monoynes as well as terminal monoynes could be used. The reaction tolerates a broad range of functional groups such as alcohol, amine, alkene, ether, halogen, and nitrile. The reaction of 1,6-octadiyne derivatives with 1-alkynes gives ortho products and meta products. The regioselectivity could be controlled by the choice of ligand. The reaction with DPPE was meta selective, with meta selectivity of up to 82%. The reaction with DPPF was ortho selective, with ortho selectivity of up to 88%. We propose a mechanism to account for this regioselective cycloaddition. [Ir(cod)Cl](2)/DPPE also catalyzed the cycloaddition of alpha,omega-diynes with 2,5-dihydrofuran to give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and n-butyl vinyl ether gave benzene derivatives instead of cyclohexadiene derivatives. We also propose a mechanism to account for this novel aromatization that includes cleavage of the C-O bond.