Metathesis Step Research Articles

Mechanistic studies on acetylene cyclotrimerization catalyzed by Grubbs first and second generation catalysts

Cyclotrimerization of acetylene by Grubbs first and second generation CC bond metathesis catalysts has been attempted by experimentalists with limited success and lack of reliable information about the mechanism of the reaction hinders further progress in the development of efficient catalysts. Herein, we describe a systematic density functional theory study on the probable mechanisms of this reaction and show that it proceeds through either a fully metathesis pathway (pathway 1) or through an alternate non-metathesis pathway (pathway 2). Pathway 1 consists of four metathesis steps characterized by the formation of metallacyclobutene-like intermediate in each step while pathway 2 passes through a metallacyclopentadiene intermediate. In metathesis pathway, the final ring closing metathesis step for benzene formation competes with another cross metathesis propagation step towards polyene chain expansion. Pathways 1 and 2 show a highly exothermic ∼120kcal/mol reaction profile due to the tremendous energy gain in converting acetylene triple bonds to aromatic bonds. The reaction is highly influenced by the choice of ligands in the catalyst design, particularly, by reducing the steric influence of ligands, cyclotrimerization of acetylene to benzene appears as a feasible process by Grubbs-type catalysts.

Synthesis and transport of impurities in electrodialysis metathesis: Production of choline dihydrogen phosphate

The production of ionic liquids involves a metathesis step in which the desired anion and cation are combined. Depending on the desired product purity, this step can be accomplished by different methods, including acid base neutralisation reactions, the use of silver salts and electrodialysis. In this paper, electrodialysis metathesis is used for the production of choline dihydrogen phosphate. The influence of operating parameters was investigated. It was found that a high current density, low diluate and choline dihydrogen phosphate concentration yield the highest product purity. Furthermore, it was illustrated for the first time that electrodialysis metathesis is able to yield a product purity comparable with that obtained by using silver salts. An electrical efficiency of 94.0% for choline and 58.6% for dihydrogen phosphate was achieved. The total cost of the electrodialysis process was estimated at 0.06€ per mole of choline dihydrogen phosphate. The second aim of this paper is the characterization of the flow of impurities in electrodialysis metathesis. In addition, the effect of operating variables on this flow of impurities was quantified. In the further optimization of the electrodialysis metathesis process, this knowledge is likely to be of great interest in conducting salt metathesis reactions.

Chain Multiplication of Fatty Acids to Precise Telechelic Polyethylene

AbstractStarting from common monounsaturated fatty acids, a strategy is revealed that provides ultra‐long aliphatic α,ω‐difunctional building blocks by a sequence of two scalable catalytic steps that virtually double the chain length of the starting materials. The central double bond of the α,ω‐dicarboxylic fatty acid self‐metathesis products is shifted selectively to the statistically much‐disfavored α,β‐position in a catalytic dynamic isomerizing crystallization approach. “Chain doubling” by a subsequent catalytic olefin metathesis step, which overcomes the low reactivity of this substrates by using waste internal olefins as recyclable co‐reagents, yields ultra‐long‐chain α,ω‐difunctional building blocks of a precise chain length, as demonstrated up to a C48 chain. The unique nature of these structures is reflected by unrivaled melting points (Tm=120 °C) of aliphatic polyesters generated from these telechelic monomers, and by their self‐assembly to polyethylene‐like single crystals.

Chain Multiplication of Fatty Acids to Precise Telechelic Polyethylene.

Starting from common monounsaturated fatty acids, a strategy is revealed that provides ultra-long aliphatic α,ω-difunctional building blocks by a sequence of two scalable catalytic steps that virtually double the chain length of the starting materials. The central double bond of the α,ω-dicarboxylic fatty acid self-metathesis products is shifted selectively to the statistically much-disfavored α,β-position in a catalytic dynamic isomerizing crystallization approach. "Chain doubling" by a subsequent catalytic olefin metathesis step, which overcomes the low reactivity of this substrates by using waste internal olefins as recyclable co-reagents, yields ultra-long-chain α,ω-difunctional building blocks of a precise chain length, as demonstrated up to a C48 chain. The unique nature of these structures is reflected by unrivaled melting points (Tm =120 °C) of aliphatic polyesters generated from these telechelic monomers, and by their self-assembly to polyethylene-like single crystals.

Consequences of Surface Oxophilicity of Ni, Ni-Co, and Co Clusters on Methane Activation.

This study describes a new C-H bond activation pathway during CH4-CO2 reactions on oxophilic Ni-Co and Co clusters, unlike those established previously on Ni clusters. The initial C-H bond activation remains as the sole kinetically relevant step on Ni-Co, Ni, and Co clusters, but their specific reaction paths vary. On Ni clusters, C-H bond activation occurs via an oxidative addition step that involves a three-center (H3C···*···H)⧧ transition state, during which a Ni-atom inserts into the C-H bond and donates its electron density into the C-H bond's antibonding orbital. Ni-Co clusters are more oxophilic than Ni; thus, their surfaces are covered with oxygen adatoms. An oxygen adatom and a vicinal Co-atom form a metal-oxygen site-pair that cleaves the C-H bond via a σ bond metathesis reaction, during which the Co inserts into the C-H bond while the oxygen abstracts the leaving H-atom in a concerted, four-center (H3C···*···H···O*)⧧ transition state. Similarly, Co clusters also catalyze the σ bond metathesis step, but much less effectively because of their higher oxophilicities, much stronger binding to oxygen, and less effective hydrogen abstraction than Ni-Co clusters. On Ni-Co and Co clusters, the pseudo-first-order rate coefficients are single-valued functions of the CO2-to-CO ratio (or H2O-to-H2 ratio), because this ratio prescribes the oxygen chemical potentials and the relative abundances of metal-oxygen site-pairs through the water-gas shift equilibrium. The direct involvement of reactive oxygen in the kinetically relevant step leads to more effective CH4 turnovers and complete elimination of coke deposition on Ni-Co bimetallic clusters.

Intramolecular Quaternization as Folding Strategy for the Synthesis of Catalytically Active Imidazolium-Based Single Chain Nanoparticles.

A novel synthetic strategy to single chain nanoparticles (SCNP) based on a previously unexplored intramolecular reaction as a means to autonomously fold a parent copolymer precursor is reported. The latter is a statistical styrenic-type copolymer synthesized by RAFT polymerization and is composed of four different comonomer units, including styrene, grafted poly(ethylene oxide) chains, and antagonist benzimidazol- and chlorobenzyl-based units. The two latter functions are reacted together by a quaternization reaction to spark the folding process, creating imidazolium-based cross-link points. Formation of SCNP with a hydrodynamic diameter <10 nm is established by a combination of different characterization techniques. A subsequent metathesis step for exchanging chloride anions by acetate ones of imidazolium moieties enables a use of SCNP for the organocatalyzed benzoin condensation, thanks to the ability of imidazolium acetate to generate SCNP-supported N-heterocyclic carbenes as organocatalysts.

Dehydrogenative B−H/C(sp3)−H Benzylic Borylation within the Coordination Sphere of Platinum(II)

AbstractThe first examples of stoichiometric dehydrogenative B−H/C(sp3)−H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2‐P,N)Pt(η3‐benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ‐bond metathesis steps, whereby a PtII−H intermediate engages in C(sp3)−H bond activation‐induced dehydrogenation.

Dehydrogenative B-H/C(sp3 )-H Benzylic Borylation within the Coordination Sphere of Platinum(II).

The first examples of stoichiometric dehydrogenative B-H/C(sp3 )-H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2 -P,N)Pt(η3 -benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ-bond metathesis steps, whereby a PtII -H intermediate engages in C(sp3 )-H bond activation-induced dehydrogenation.

Copper-Catalyzed Borylstannylation of Alkynes with Tin Fluorides

Tin fluorides were found to be suitable electrophiles for the copper-catalyzed borylstannylation of terminal alkynes with bis(pinacolato)diboron to afford cis-vic-boryl(stannyl)alkenes straightforwardly. A fluorine atom proved to play a pivotal role in generating a key catalytic intermediate, a borylcopper species, both in the induction period and in the σ-bond metathesis step.

Metathesis Mechanism of Zinc-Catalyzed Fluorination of Alkenes with Hypervalent Fluoroiodine

Density functional theory calculations are used to unravel the mechanism of the Zn-catalyzed fluorocyclization reaction of alkenes using fluoro-benziodoxole reagent. In the initial step Zn coordinates to the fluorine atom of the fluoro-benziodoxole reagent. An important activation step for the fluorination involves Zn-mediated isomerization of the benziodoxole reagent. The activation is followed by a metathesis step to form the C–F bond and a nucleophilic substitution, closing the ring to yield the final aminofluorination product. This mechanism has feasible energy barriers and accounts for the observed selectivity outcome. An alternative mechanism involving an iodocyclopropylium cation intermediate is shown to be associated with high energies.

Poly(N-alkyl-3,6-carbazole)s via Kumada Catalyst Transfer Polymerization: Impact of Metal–Halogen Exchange

The preparation of poly(3,6-carbazole) via Kumada catalyst transfer polymerization (KCTP) is investigated and analyzed in detail by mass spectrometry to explore the scope of the applied protocols. Namely, common magnesium reagents were screened for the initial Grignard metathesis (GRIM) step and subsequently polymerized using [Ni(dppp)Cl2] (dppp is 1,3-bis(diphenylphosphanyl)propane). The metal–halogen exchange was monitored by GC, while the polymers were characterized by size exclusion chromatography (SEC) and 1H NMR spectroscopy. More importantly, the polymer end groups were investigated by means of mass spectrometry and isotope analysis, which revealed significant deviation from the chain-growth character of related poly(3-hexylthiophene). It was found that standard Grignard reagents led to incomplete GRIM even under extended reaction times and elevated temperatures, while the presence of LiCl greatly accelerated the metal–halogen exchange and also the KCTP. According to end-group analysis of the obtained polymers, side reactions occur that are attributed and explained in terms of catalyst dissociation and/or disproportionation. Namely, the replacement of the bromo-substituents by either alkyl groups via transmetalation or hydrogen via β-hydride elimination was observed. Finally, quantitative metal–halogen exchange was achieved using a magnesiate reagent, which also afforded the corresponding polymer in good isolated yield (66%). The end-group scrambling, dispersity, and observed molar masses support the proposed role of catalyst dissociation and/or disproportionation, even in the absence of excess of residual Grignard reagent.

Tricoordinate Organochromium(III) Complexes Supported by a Bulky Silylamido Ligand Produce Ultra‐High‐Molecular Weight Polyethylene in the Absence of Activators

Low‐coordinate organoCr(III) complexes supported by the silylamido ligand –N(SiMe3)DIPP (DIPP = 2,6‐diisopropylphenyl) are ethylene polymerization catalyst precursors without the need of additional cocatalyst. The reaction of CrCl3(THF)3 with 3 or 2 equiv. of LiN(SiMe3)DIPP yields either a four‐membered cyclometalated Cr complex or Cr[N(SiMe3)DIPP]2Cl, respectively, with no trace of Cr[N(SiMe3)DIPP]3. Addition of 1 equiv. of LiN(SiMe3)DIPP to Cr[N(SiMe3)DIPP]2Cl also leads to the four‐membered metallacycle, which upon heating transforms to a new six‐membered Cr metallacycle, likely via a σ‐bond metathesis step. Cr[N(SiMe3)DIPP]2Cl can be readily converted to bis(amido)Cr(III) vinyl and alkyl complexes Cr[N(SiMe3)DIPP]2R (R = vinyl, Bn, and Me). All of these structurally characterized low‐coordinate Cr(III) complexes with a Cr–C bond initiate the polymerization of ethylene in the absence of activators or cocatalysts, producing ultra‐high‐molecular weight polyethylene.

ChemInform Abstract: Tandem Olefin Metathesis/Oxidative Cyclization: Synthesis of Tetrahydrofuran Diols from Simple Olefins.

AbstractA one‐pot tandem process consisting of an olefin metathesis step and an oxidative cyclization is developed to construct 2,5‐disubstituted tetrahydrofurans in a highly stereocontrolled manner.

Impact of Ligand and Silane on the Regioselectivity in Catalytic Aldehyde–Alkyne Reductive Couplings: A Theoretical Study

The reaction mechanisms of the (NHC)Ni(0)-catalyzed aldehyde–alkyne reductive couplings with silanes as reducing agent have been theoretically investigated with the aid of DFT calculations. The impacts of N-heterocyclic carbene (NHC) ligands and silanes on the reversal of regioselectivity and the rate-limiting step alteration were rationalized. It is found that the steric effects play a dominant role. The reversal of the regioselectivity is found to be related to the switching of the steric effect, from the aldehyde phenyl hindrance with the adjacent alkyne substituent to the NHC ligand hindrance with the adjacent alkyne substituent, when the NHC ligand employed is changed from small to large. The rate-limiting step alteration caused by using bulkier silanes is due to the generated strong steric effect, which makes the σ-bond metathesis transition state relatively high in enthalpic energy, thus with the entropy penalty making the metathesis step rate-limiting instead of the oxidative cyclization step.

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks.

The cross metathesis of 1,2-epoxy-5-hexene (1) with methyl acrylate and acrylonitrile was investigated as an entry to the synthesis of polyfunctional compounds. The resulting cross metathesis products were hydrogenated in a tandem fashion employing the residual ruthenium from the metathesis step as the hydrogenation catalyst. Interestingly, the epoxide ring remained unreactive toward this hydrogenation method. The saturated compound resulting from the cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields.

Two Ene-Yne Metathesis Approaches to the Total Synthesis of Amphidinolide P.

The total synthesis of amphidinolide P was achieved through two different ene-yne metathesis approaches. In each approach, the metathesis step was performed at late stages in the synthesis with all other functionality present. By forging two successful pathways to the synthesis of 1, some of the strengths and weaknesses of metathesis-intensive synthetic strategies were identified.

Theoretical Studies on the Mechanism of Iridium-Catalyzed Alkene Hydrogenation by the Cationic Complex [IrH2(NCMe)3(PiPr3)]+

A mechanistic DFT study has been carried out on the ethene hydrogenation catalyzed by the [IrH2(NCMe)3(PiPr3)]+ complex (1). First, the reaction of (1) with ethene has been theoretically characterized, and three mechanistic proposals (A–C) have been made for an identification of the preferred pathways for the alkene hydrogenation catalytic cycle considering Ir(I)/Ir(III) and Ir(III)/Ir(V) intermediate species. Theoretical calculations reveal that the reaction path with the lowest energy starts at an initial ethene migratory insertion into the metal–hydride bond, followed by dihydrogen coordination into the vacancy. Ethane is formed via σ-bond metathesis between the bound H2 and the Ir-ethyl moiety, being the rate-determining step, in agreement with the experimental data available. The calculated energetic span associated with the catalytic cycle is 21.4 kcal mol–1. Although no Ir(V) intermediate has been found along the reaction path, the Ir(V) nature of the transition state for the proposed key σ-bond metathesis step has been determined by electron localization function and geometrical analysis.

Synthesis of Hydrogen‐Bond Surrogate α‐Helices as Inhibitors of Protein‐Protein Interactions

The α-helix is a prevalent secondary structure in proteins and is critical in mediating protein-protein interactions (PPIs). Peptide mimetics that adopt stable helices have become powerful tools for the modulation of PPIs in vitro and in vivo. Hydrogen-bond surrogate (HBS) α-helices utilize a covalent bond in place of an N-terminal i to i+4 hydrogen bond and have been used to target and disrupt PPIs that become dysregulated in disease states. These compounds have improved conformational stability and cellular uptake as compared to their linear peptide counterparts. The protocol presented here describes current methodology for the synthesis of HBS α-helical mimetics. The solid-phase synthesis of HBS helices involves solid-phase peptide synthesis with three key steps involving incorporation of N-allyl functionality within the backbone of the peptide, coupling of a secondary amine, and a ring-closing metathesis step.

ChemInform Abstract: Intramolecular Transannulation of Alkynyl Triazoles via Alkyne—Carbene Metathesis Step: Access to Fused Pyrroles.

An intramolecular Rh-catalyzed transannulation reaction of alkynyl triazoles has been developed. This method allows efficient construction of various 5,5-fused pyrroles, including tetrahydropyrrolo and spiro systems. The method demonstrates excellent functional group compatibility. A rhodium carbene–alkyne metathesis mechanism is proposed for this transformation.

Grubbs cross-metathesis pathway for a scalable synthesis of γ-keto-α,β-unsaturated esters.

A direct and scalable route to γ-keto-α,β-unsaturated esters, useful intermediates in medicinal chemistry and natural products synthesis, is reported. The key step involves the use of Grubbs’ second-generation olefin metathesis catalyst for cross-metathesis of alkyl acrylates and 2° allylic alcohols. The metathesis step is followed by oxidation to give the desired products in high yield on scales of up to 25 g.