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The carbonyl‐alkyne metathesis reaction is a powerful method for the synthesis of α,β‐unsaturated carbonyls. We now report on the development of a halogen‐bond catalyzed protocol for both the intra‐ and intermolecular reaction. Our studies revealed that methanol is a highly efficient solvent and that a very broad range of functional groups are tolerated under the reaction conditions. Mechanistic studies support the proposed halogen‐bond interaction. Furthermore, the halogen‐bond protocol is compared with other available catalytic systems for these reactions. [ABSTRACT FROM AUTHOR]

This manuscript describes a new strategy for prodrug synthesis in which a relatively inert ether group is introduced at an early stage in a synthetic sequence and functionalized in the final step to introduce a prodrug‐activating group through a chemoselective process. Boryl allyloxy (BAO) ether groups are synthesized through several metal‐mediated processes to form entities that are readily cleaved under oxidative conditions commonly found in cancer cells. The high cleavage propensity of the BAO group allows for ether cleavage, making these compounds substantially more hydrolytically stable in comparison to acyl‐linked prodrugs while retaining the ability to release alcohols. We report the preparation of prodrug analogues of the natural products camptothecin and pederin from acetal precursors that serve as protecting groups in their synthetic sequences. The BAO acetal groups cleave in the presence of hydrogen peroxide to release the cytotoxic agents. The pederin‐based prodrug shows dramatically greater cytotoxicity than negative controls and outstanding selectivity and potency toward cancer cell lines in comparison to non‐cancerous cell lines. This late‐stage functionalization approach to prodrug synthesis should be applicable to numerous systems that can be accessed through chemoselective processes. [ABSTRACT FROM AUTHOR]

A highly efficient, convenient and ecofriendly approach to access highly functionalized 2H‐chromenes via intramolecular aldehyde alkyne metathesis reaction was established starting from readily accessible alkyne‐tethered 2‐((3‐phenylprop‐2‐yn‐1‐yl) oxy)benzaldehydes and catalyzed by silica sulfuric acid (SiO2‐OSO3H, SSA) coupled with microwave irradiation. This reaction was well tolerated for various substituents including different functional groups and furnished the desired highly functionalized 2H‐chromene derivatives in good to excellent yields in a very short time. A systematic study of the conventional heating approach and microwave irradiation was performed to demonstrate the advantages of the microwave‐assisted condition in terms of high yield and shorter reaction time. [ABSTRACT FROM AUTHOR]

Ring‐opening metathesis polymerization (ROMP) is an effective method for synthesizing functional polymers, but since the technique typically relies on high ring strain cyclic olefins, the most common monomers are norbornene derivatives. The reliance on one class of monomer limits the obtainable properties of ROMP polymers. In this work, we investigate new bicyclic monomers synthesized via epoxidation of commercial dienes. DFT estimates of these monomers’ ring strains suggests a significant increase in strain for cyclic olefins containing allylic epoxides. We found that the eight‐membered (3,4‐COO) and five‐membered (CPO) cyclic olefins were particularly effective for ROMP. CPO was of especially intriguing due to its excellent polymerizability when compared to the limited reactivity of other five‐membered rings. Unlike polynorbornenes, the resulting polymers of both monomers displayed glass transition temperatures well below room temperature. Interestingly, poly(3,4‐COO) showed both high stereo‐ and regioregularity while poly(CPO) showed little regularity. Both polymers could be readily modified via post‐polymerization ring‐opening of the reactive allylic epoxides. With a high epoxide density in poly(CPO), CPO is an exciting new ROMP monomer that is easily synthesized, can be polymerized to high conversion at room temperature, and may be facilely modified to yield a wide range of functional materials. [ABSTRACT FROM AUTHOR]

We report the synthesis and full characterization of the copper dinitrogen complex [(η1‐N2)Cu{Al(ORF)4}] 2 (RF=C(CF3)3) prepared by a cascade metathesis reaction of Ag[Al(ORF)4] with CuI‐excess in iso‐perfluorohexane (i‐pfh) under N2 atmosphere. Title compound 2 features an extraordinarily high N2 stretching frequency at 2313/2314 cm−1 (IR/Raman) and was characterized by single‐crystal and powder X‐ray diffractometry. Quantum chemical charge displacement analysis based on natural orbitals of chemical valence (CD‐NOCV) indicates that the copper‐dinitrogen interaction is still governed by weak π‐backdonation, but is significantly reduced compared to all literature‐known transition metal dinitrogen complexes. [ABSTRACT FROM AUTHOR]

The strasseriolide macrolides show promising in vitro and in vivo activities against P. falciparum and T. cruzi, the parasites causing malaria and Chagas disease, respectively. However, the as yet poor understanding of structure/activity relationships and the fact that one family member proved systemically toxic for unknown reasons render a more detailed assessment of these potential lead compounds difficult. To help overcome these issues, a collective total synthesis was devised. The key steps consisted of a ring closing alkyne metathesis (RCAM) reaction to forge a common macrocyclic intermediate followed by a hydroxy‐directed ruthenium catalyzed trans‐hydrostannation of the propargyl alcohol site thus formed. The resulting alkenyltin derivative served as the central node of the synthesis blueprint, which could be elaborated into the natural products themselves as well as into a set of non‐natural analogues according to the concept of diverted total synthesis. The recorded biological data confirmed the potency of the compounds and showed the lack of any noticeable cytotoxicity. The "northern" allylic alcohol subunit was recognized as an integral part of the pharmacophore, yet it provides opportunities for chemical modification. [ABSTRACT FROM AUTHOR]

We report here the preparation and characterization of new well‐defined silica‐supported Ti imido complexes that present an L‐ligand variation in a structure of currently the most active oxo/imido heterometathesis catalyst (≡SiO)Ti(=NtBu)(Me2Pyr)(py)2 (1s), where py is replaced with stronger electron‐donating 4‐(N,N‐dimethylamino)pyridine (2s) or bidentate 2,2′‐bipyridine (3s). The materials were characterized with elemental and mass balance analyses and IR and solid‐state NMR that confirmed the selective formation of surface Ti species with terminal imido ligand. Evaluation of the catalytic oxo/imido heterometathesis activity of the obtained materials demonstrated that L‐ligands have a pronounced influence on the catalytic performance. In particular, the replacement of pyridine with stronger donating ligands resulted in a significant drop of activity. The catalytic results are discussed in view of the reaction mechanism and implications for further catalyst development. [ABSTRACT FROM AUTHOR]

Continuing our investigation of catalytic oxo/imido heterometathesis as novel water‐free method for C=N bond construction, we report here the application of classical transition metal oxides dispersed on silica (MOx/SiO2, M=V, Mo, W) as cheap, robust and readily available alternative to the catalysts prepared via Surface Organometallic Chemistry (SOMC). The oxide materials demonstrated activity in heterometathetical imidation of ketones, WO3/SiO2 being the most efficient. We also describe a new well‐defined supported W imido complex (≡SiO)W(=NMes)2(Me2Pyr) (Mes=2,4,6‐Me3C6H2, Me2Pyr=2,5‐dimethylpyrrolyl) and characterize it with SOMC protocols, which allowed us to identify the position of W on the oxo/imido heterometathesis activity scale (Mo

A unified approach to access the naturally occurring cyclic tetrapeptide JM‐47 and some of its structural variants from a common macrocyclic scaffold has been developed. The key reactions involved a difficult macrocyclization to access the scaffold, and its late‐stage diversification by cross‐metathesis to access the natural product as well as analogues. The synthesis proceeded in good overall yield and high stereochemical integrity. It also confirms the structure and configuration assigned to JM‐47. [ABSTRACT FROM AUTHOR]

Isomerization Metathesis (ISOMET) reaction is an emerging tool for "open loop" chemical recycling of polyethylene to propylene. Novel, latent N‐Alkyl substituted Cyclic(Alkyl)(Amino)Carbene (CAAC)–ruthenium catalysts (5a‐Ru, 3b‐Ru – 6c‐Ru) are developed rendering "inverted" chemical structure while showing enhanced ISOMET activity in combination with (RuHCl)(CO)(PPh3)3 (RuH) double bond isomerization co‐catalyst. Systematic investigations reveal that the steric hindrance of the substituents on nitrogen and carbon atom adjacent to carbene moiety in the CAAC ligand have significantly improved the catalytic activity and robustness. In contrast to the NHC‐Ru and CAAC‐Ru catalyst systems known so far, these systems show higher isomerization metathesis (ISOMET) activity (TON: 7400) on the model compound 1‐octadecene at as low as 3.0 bar optimized pressure, using technical grade (3.0) ethylene. The propylene content formed in the gas phase can reach up to 20% by volume. [ABSTRACT FROM AUTHOR]

The tetracyanamidometallates Li4[T(CN2)4] with T=Si, Ge were prepared by solid‐state metathesis (SSM) reactions between TI4 and Li2(CN2). The new compounds Li4[T(CN2)4] are obtained as crystalline phases in high yields and represent the most basic examples of the family of tetracyanamidometallates. The formation of these compounds, via SiI4 and Li2(CN2), is analyzed by means of differential scanning calorimetry (DSC). The [Si(CN2)4]4− ion in the structure of Li4[Si(CN2)4] can be considered an analogue to the [SiO4]4− ion in Li4SiO4. The crystal structures of Li4[T(CN2)4] were solved and refined isotypically on the basis of single‐crystal X‐ray diffraction data in the space group C2/c, and further characterized by infrared and solid‐state NMR techniques. [ABSTRACT FROM AUTHOR]

Diversity‐oriented synthesis of some novel functionalized azaheterocyclic β‐amino esters with multiple chiral centers from 1,3‐cyclooctadiene‐based β‐amino acids through a stereocontrolled synthetic route has been accomplished. The strategy was based on the creation of some novel unsaturated N‐protected cyclic β‐amino esters from 1,3‐cyclooctadiene. Products were subjected to ring‐opening metathesis (ROM) followed by selective ring‐closing metathesis (RCM). A comparative investigation on the selectivity, regarding the catalysts, yields, conversions, and substrate directing effect on ring‐rearrangement metathesis (RRM) transformation has been accomplished. Importantly, the procedure used in this synthetic process does not affect the configuration of the chiral centers. The pathway takes place across conservation of the configurations of the stereocenters; therefore, the architectural skeleton of the starting cyclooctene‐based β‐amino acids predetermined the structure of the new azaheterocyclic systems. [ABSTRACT FROM AUTHOR]

The germylone dimNHCGe (5, dimNHC=diimino N‐heterocyclic carbene) undergoes a [2+2] cycloaddition with isocyanates RNCO (R=4‐tolyl or 3,5‐xylyl) to furnish novel alkyl carboxamido germylenes 7 (R=4‐tolyl) and 8 (R=3,5‐xylyl), featuring a C−C bond between the former carbene carbon and the isocyanate moiety. Heating a mixture of 8 with 4‐tolyl isocyanate to 100 °C results in isocyanate metathesis, demonstrating reversible C−C bond formation on the reduced germanium compound. DFT calculations suggest that this process occurs via the reductive dissociation of isocyanate from 8 that regenerates the parent Ge(0) compound 5. [ABSTRACT FROM AUTHOR]

The preparation and characterization of six rare earth 2‐methyl‐3‐furoate (2m3fur) complexes are detailed in this study. Analysis through single‐crystal X‐ray diffraction, as well as powder XRD, reveals that all six compounds belong to one of two structural groups: {[RE2(2m3fur)6(EtOH)] ⋅ H2O}n (RE=La, Ce, Pr) and [RE3(2m3fur)9]n (RE=Y, Er, Yb). These structural groups feature carboxylate coordinated linear polymers. The former complexes have two distinct metal centers, one ten coordinate and one nine, with lattice water participating in a hydrogen bond with coordinated ethanol. The latter structures, involving erbium, ytterbium, and yttrium, have three unique metal centers: two eight coordinate, and one seven‐coordinated. In corrosion inhibition tests on mild steel in 0.01 M NaCl solution, the maximum efficiency was observed with [Y3(2m3fur)9]n at 59 %, which is less effective than yttrium 3‐furoate (90 % efficiency). The results suggest that the steric effect of the methyl group adversely affects corrosion inhibition. [ABSTRACT FROM AUTHOR]

The beauty of one‐pot cascade reaction lies in the efficient disconnection and construction of several bonds in a single reaction flask, without the isolation of any intermediates. Herein, we report the first photoinduced thermally promoted cascade reactions of readily available aromatic ketones and aromatic gem‐difluoroalkenes for the synthesis of phenanthrenes which possess potential utility in drug design and materials science. The reaction combines carbonyl‐olefin metathesis (cascade photoinduced [2+2] cyclization and thermally controlled retro [2+2] cyclization) and dehydrogenative cyclization (cascade photoinduced conrotatory 6π electrocyclization and collidine‐promoted dehydrogenative aromatization) together in one pot. The oxidant‐free, acid‐free and metal‐free reaction shows broad substrate scope and wide functional group tolerance. [ABSTRACT FROM AUTHOR]

Macrocycles with bent π‐conjugation motif are extremely rare in nature and synthetically daunting and anticancer haouamines and spirohexenolides were representative of such rare natural products with synthetically challenging bent π‐conjugation within a macrocycle. While the total synthesis of haouamines has been elegantly achieved, spirohexenolides remains an unmet synthetic challenge due to the highly strained bent 1,3,5‐triene conjugation within C15 macrocycle. Inspired by the chemical synthesis of cycloparaphenylenes (CPPs) and haouamines, herein we devise a synthetic strategy to overcome the highly strained bent 1,3,5‐triene conjugation within the macrocycle and achieve the first, asymmetric total synthesis of spirohexenolides A (>20 mg) and B (>50 mg). Our synthesis features strategic design of ring‐closing metathesis (RCM) macrocyclization followed by double dehydration to achieve the C15 macrocycle with the deformed nonplanar 1,3,5‐triene conjugation. In addition, we have developed a new enantioselective construction of highly functionalized spirotetronate fragment (northeast moiety) through RCM and Ireland–Claisen rearrangement. Our in vitro bioassay studies reveal that both spirohexenolides are cytotoxic against a panel of human cancer cells with IC50 1.2–13.3 μM and spirohexenolide A is consistently more potent (up to 3 times) than spirohexenolide B, suggesting the importance of alcohol for their bioactivity and for medicinal chemistry development. [ABSTRACT FROM AUTHOR]

Atropisomers – separable conformers that arise from restricted single‐bond rotation – are frequently encountered in medicinal chemistry. However, preparing such compounds with the desired configuration can be challenging. Herein, we present a biocatalytic strategy for achieving atroposelective synthesis relying on artificial metalloenzymes (ArMs). Based on the biotin‐streptavidin technology, we constructed ruthenium‐bearing ArMs capable of producing atropisomeric binaphthalene compounds through ring‐closing metathesis in aqueous media. Further, we show that atroposelectivity can be fine‐tuned by engineering two close‐lying amino acid residues within the streptavidin host protein. The resulting ArMs promote product formation with enantiomeric ratios of up to 81 : 19, while small‐molecule catalysts for atroposelective metathesis under aqueous reaction conditions are yet unknown. This study represents the first demonstration that stereoselective metathesis can be achieved by an artificial metalloenzyme. [ABSTRACT FROM AUTHOR]

We describe the facile synthesis of [(Me3Si)2CH]2E=PMes* (E=Ge, Sn) from the reaction of the tetrylenes with the phospha‐Wittig reagent, Me3P−PMes*. Their reactivity towards a range of substrates with protic and hydridic E−H bonds (E=N, O, Si) is described. In addition to hydroelementation reactions of the E=P bonds, we show that these compounds, particularly [(Me3Si)2CH]2Sn=PMes*, also act as base‐stabilized phosphinidenes, allowing phosphinidene transfer to other nucleophiles. [ABSTRACT FROM AUTHOR]

In this account our aim was to give an insight into the application of metathesis protocols (ROM, RCM, RCEYM, CM, RRM) for the synthesis of various azaheterocyclic frameworks. Due to the high biological potential and importance in peptide chemistry and drug design of β‐amino acids our intention is to give a highlight on the synthetic procedures and transformation of these class of compounds with the above‐mentioned metathesis strategies with emphasis on selectivity, stereocontrol, substrate‐directing effect or functional group tolerance. [ABSTRACT FROM AUTHOR]

Terminal aluminium and gallium imides of the type K[(NON)M(NR)], bearing heteroatom substituents at R, have been synthesised via reactions of anionic aluminium(I) and gallium(I) reagents with silyl and boryl azides (NON=4,5‐bis(2,6‐diisopropyl‐anilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethyl‐xanthene). These systems vary significantly in their lability in solution: the N(SiiPr3) and N(Boryl) complexes are very labile, on account of the high basicity at nitrogen. Phenylsilylimido derivatives provide greater stabilization through the π‐acceptor capabilities of the SiR3 group. K[(NON)AlN(SitBuPh2)] offers a workable compromise between stability and solubility, and has been completely characterized by spectroscopic, analytical and crystallographic methods. The silylimide species examined feature minimal π‐bonding between the imide ligand and aluminium/gallium, with the HOMO and HOMO‐1 orbitals effectively comprising orthogonal lone pairs centred at N. Reactivity‐wise, both aluminium and gallium silylimides can act as viable sources of nitride, [N]3−, with systems derived from either metal reacting with CO to afford cyanide complexes. By contrast, only the gallium system K[(NON)Ga{N(SiPh3)}] is capable of effecting a similar transformation with N2O to yield azide, N3−, via formal oxide/nitride metathesis. The aluminium systems instead generate RN3 via transfer of the imide fragment [RN]2−. [ABSTRACT FROM AUTHOR]

The metathesis of ethylene with 2‐butenes to propene is an established large‐scale process. However, the fundamentals behind in situ transformation of supported WOx, MoOx, or ReOx species into catalytically active metal‐carbenes and the intrinsic activity of the latter as well as the role of metathesis‐inactive cocatalysts are still unsolved. This is detrimental for catalyst development and process optimization. In this study, we provide the required essentials derived from steady‐state isotopic transient kinetic analysis. For the first time, the steady‐state concentration, the lifetime, and the intrinsic reactivity of metal carbenes were determined. The obtained results can be directly used for the design and the preparation of metathesis‐active catalysts and cocatalysts, thereby opening up possibilities for optimizing propene productivity. [ABSTRACT FROM AUTHOR]

A facile and efficient synthesis of 3‐spiro cycloalkene fused 7‐aza‐2‐indalones from 3,3′‐di‐ or N,3,3′‐tri‐ allyl/homoallyl/pentenyl 7‐aza‐2‐indalones via ring‐closing metathesis (RCM) using Grubbs‐II catalyst has been achieved. The scope of the reaction has been demonstrated by synthesizing spiro products of various ring sizes (n=5, 7, and 18), utilizing 2‐indalone/7‐azaindalone and various alkenylation agents such as allyl/homoallyl/pentenyl bromides as substrates. In addition to usual RCM products, a cross metathesis (CM) product was observed when the substrate was N,3,3′‐triallylated derivative from 2‐indalone. Notably, a macrocyclic, 18‐membered bis‐spirodiene of N‐methyl‐7‐azaindalone was observed by means of intermolecular ring‐closing metathesis (RCM‐RCM). Also, Structures of a few representative spiro‐annulated products were evidenced with single crystal XRD analysis. Furthermore, a plausible mechanism for the products is discussed. [ABSTRACT FROM AUTHOR]

Herein, we report the 16‐ and 19‐membered macrocycles which are closely resembles structurally musk like compounds such as "muscone". These macrocycles were prepared starting from 12‐membered cyclododecanone and 15‐membered cyclopentadecanone ring systems respectively. Like muscone, these compounds have a methyl and keto groups embedded within the macrocyclic ring system. The key reactions include, ring‐closing metathesis (RCM) and Tebbe olefination which are highly efficient and easy to perform. This strategy is very useful in the formation of macrocyclic systems. [ABSTRACT FROM AUTHOR]

The vastness of the scale of the plastic waste problem will require a variety of strategies and technologies to move toward sustainable and circular materials. One of these strategies to address the challenge of persistent fossil‐based plastics is new catalytic processes that are being developed to convert recalcitrant waste such as polyethylene to produce propylene, which can be an important precursor of high‐performance polymers that can be designed to biodegrade or to degrade on demand. Remarkably, this process also enables the production of biodegradable polymers using renewable raw materials. In this Perspective, current catalyst systems and strategies that enable the catalytic degradation of polyethylene to propylene are presented. In addition, concepts for using "green" propylene as a raw material to produce compostable polymers is also discussed. [ABSTRACT FROM AUTHOR]

Metallacyclobutanes are intermediates in several catalytic cycles such as olefin metathesis and cyclopropanation. Furthermore, nickel is attracting attention as a versatile, earth‐abundant metal in developing new homogeneous catalytic transformations. In this context, the current literature on nickelacyclobutanes and their role in catalysis is reviewed. First, catalytic reactions involving a (putative) nickelacyclobutane intermediate are discussed, including cyclopropanations and various transformations of methylenecyclopropane. Second, studies of the stoichiometric reactivity of nickelacyclobutanes relying on their direct observation or even isolation are detailed. In particular, the relationship between the structure of nickelacyclobutanes and their reactivity is highlighted. Finally, future prospects for the development of new catalytic transformations relying on nickelacyclobutane intermediates are briefly outlined. [ABSTRACT FROM AUTHOR]

As the first known example of ring‐opening cross metathesis (ROCM) of polyfluorinated strained cyclobutenes, ROCM of 3,3,4,4‐tetrafluorocyclobutene with electronically rich alkenes, catalyzed by Grubbs or Hoveyda‐Grubbs 2nd generation precatalysts, gave a small library of non‐symmetrical isolated dienes bearing a tetrafluoroethylene spacer between the double bonds. 1‐Butoxy‐3,3,4,4‐tetrafluorohexa‐1,5‐diene thus formed underwent subsequent regioselective cross metathesis (CM) with a series of styrenes, catalyzed by Hoveyda‐Grubbs 2nd generation precatalyst, leading to non‐symmetrically substituted dienes. 6,6‐Dibutoxy‐3,3,4,4‐tetrafluorohex‐1‐ene, formed by regioselective butoxylation of 1‐butoxy‐3,3,4,4‐tetrafluorohexa‐1,5‐diene, was dihydroxylated and cyclized to the corresponding 3,3,4,4‐tetrafluorohexopyranose. [ABSTRACT FROM AUTHOR]

We report a short synthetic approach to various tricyclic systems that are present in several diquinane‐based natural products starting with a readily available exo‐dicyclopentadiene‐1‐one. To this end, we have successfully assembled a fused 5/5/7‐tricyclic enone via ring‐rearrangement metathesis as a key step. The strategy has been further extended to synthesize the 1,3‐dihydroxy and then 1‐keto‐3‐hydroxy derivatives by utilizing regio‐ and stereoselective epoxidation and ring‐rearrangement metathesis reactions as key steps. All these target compounds are found to be present in diquinane‐based natural products such as longeracinphyllins A, himalenine D and daphnipaxianine A, etc. Moreover, the newly synthesized tricyclic compounds matches the exact ring‐junction stereochemistry (5/5‐exo) of these natural products. Hence, the synthetic studies disclosed here may be useful in the synthesis of biologically significant natural products and in the drug design. The newly synthesized molecules were characterized by NMR and HRMS data. Some of these structures were confirmed by a single crystal X‐ray diffraction studies. [ABSTRACT FROM AUTHOR]

Herein, a short synthetic approach to linearly fused tricyclic enone 1 and cis‐anti‐cis type hydroxy‐triquinane 2 has been described in an efficient manner by employing tandem‐metathesis as a key step. The triquinane‐based enone 1 is prepared by a Babler–Dauben oxidation of hydroxy‐triquinane 2, which is assembled by following a three‐step sequence involving a regio‐ and stereoselective allylation, vinyl Grignard addition, and tandem‐metathesis. Our strategy relies on exo‐tricyclic ketone, which is derived from readily available exo‐dicyclopentadiene‐1‐one. The newly synthesized molecules were identified and characterized by nuclear magnetic resonance spectroscopy (NMR), and high‐resolution mass spectrometry (HRMS) data. It is worth mentioning that tricyclic enone 1 is present as a core unit of many naturally occurring polyquinanes, particularly xeromphalinone family members. Hence, our approach may be useful in the synthesis of such bioactive molecules. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Two‐electron reduction of [N2NBn]TiIVCl2 (3) gave a highly reactive [N2N]TiII species, which underwent C—O bond activation of THF (tetrahydrofuran) to generate [N2NBn]TiIV[O(CH2)4] (4) through oxidative addition. The resulted TiIV–Csp3 bond in oxametallacyclohexane was tantamount to the elaborately‐designed Ti‐alkyl complexes, competent to activate intramolecular Csp2–H bond, forming ortho‐cyclometalated complex [N2NCH2C6H4]TiIV(OnBu) (5). Key intermediates were isolated and fully characterized by X‐ray crystallography. Mechanistic studies revealed that the oxidative addition of C—O bond took place at TiII‐center via a radical intermediate, while a Csp2–H bond activation proceeded by σ‐bond metathesis with a kitelike four‐centered TiIV‐transition state. [ABSTRACT FROM AUTHOR]

Olefin metathesis catalysts like AquaMet are vulnerable to different decomposition pathways under biologically relevant conditions. Currently, stabilizing strategies are focused on approaches with limited relevance for application under biologically relevant conditions. Initial attempts to stabilise AquaMet by encapsulation within a supramolecular metallocage showed that the nitrate counterions of the cage improve the activity of the catalyst. We show that the chloride ligands of AquaMet can be replaced with nitrates by simple anion‐exchange. Catalytic studies into metathesis of a diallyl substrate showed that the presence of nitrate generates higher yields of the ring‐closed product compared to AquaMet alone, under aqueous and biological conditions. Kinetic studies support that the nitrate‐containing catalyst both initiates faster and performs catalysis at a much faster rate than AquaMet, while the rate of catalyst deactivation was similar. This new strategy of kinetic protection of a transition metal catalyst may have future applications for other catalytic reactions applied in vivo. [ABSTRACT FROM AUTHOR]

The reactions of a terminal aluminium imide with a range of oxygen‐containing substrates have been probed with a view to developing its use as a novel main group transfer agent for the [NR]2− fragment. We demonstrate transfer of the imide moiety to [N2], [CO] and [Ph(H)C] units driven thermodynamically by Al−O bond formation. N2O reacts rapidly to generate the organoazide DippN3 (Dipp=2,6‐iPr2C6H3), while CO2 (under dilute reaction conditions) yields the corresponding isocyanate, DippNCO. Mechanistic studies, using both experimental and quantum chemical techniques, identify a carbamate complex K2[(NON)Al‐{κ2−(N,O)−N(Dipp)CO2}]2 (formed via [2+2] cycloaddition) as an intermediate in the formation of DippNCO, and also in an alternative reaction leading to the generation of the amino−dicarboxylate complex K2[(NON)Al{κ2−(O,O′)−(O2C)2N‐(Dipp)}] (via the take‐up of a second equivalent of CO2). In the case of benzaldehyde, a similar [2+2] cycloaddition process generates the metallacyclic hemi‐aminal complex, Kn[(NON)Al{κ2−(N,O)−(N(Dipp)C(Ph)(H)O}]n. Extrusion of the imine, PhC(H)NDipp, via cyclo‐reversion is disfavoured thermally, due to the high energy of the putative aluminium oxide co‐product, K2[(NON)Al(O)]2. However, addition of CO2 allows the imine to be released, driven by the formation of the thermodynamically more stable aluminium carbonate co‐product, K2[(NON)Al(κ2−(O,O′)−CO3)]2. [ABSTRACT FROM AUTHOR]

dinoflagellates amphidinolide group of natural products have drawn the attention of the synthetic community owing to their natural scarcity, variation in ring size (12‐ to 27‐membered), and architectural complexity. The manifold strategies for creating the unique macrocyclic framework of amphidinolides, overcoming the entropy barrier of cyclisation, in good yields and selectivity, are highly encouraging as this platform provides an opportunity to develop compounds for structure‐activity relationship studies. This review emphasizes various methods of intramolecular C−C and C−O bond‐forming reactions for constructing the macrocyclic structure of different naturally occurring molecules of amphidinolide family. [ABSTRACT FROM AUTHOR]

Prenylation is a ubiquitous late‐stage modification in nature that often confers significantly improved bioactivity for secondary metabolites. While this lipophilic modification renders enhanced potency, the lipophilic tag(s) can diminish bioavailability and adversely alter drug transportation and metabolism. Thus, a functional‐group‐tolerant, mild, and selective late‐stage C−H functionalization of prenyl tags would present a great potential in drug discovery programs but could also impact other fields, such as agrochemistry and chemical biology. Herein we report an exocyclic‐strain‐driven cross‐metathesis reaction of prenyl tags, a formal double C−H oxidation protocol, that can be used for the selective late‐stage derivatization of prenylated compounds and natural products. This methodology avoids the need for prefunctionalization of target molecules and affords ready access to an unprecedented library of oxo‐ and aza‐prenylated complex molecules. Thus, in a broader context, this methodology extends late‐stage functionalization beyond that available to nature. [ABSTRACT FROM AUTHOR]

Despite its relative simplicity, ethylene is an interesting molecule with wide‐ranging impact in modern chemistry and biology. Stemming from ethylene's role as a critical plant hormone, there has been significant effort to develop selective and sensitive molecular sensors for ethylene. Late transition metal complexes have played an important role in detection strategies due to ethylene's lack of structural complexity and limited reactivity. Two main approaches to ethylene detection are identified: (1) coordination‐based sensors, wherein ethylene binds reversibly to a metal center, and (2) activity‐based sensors, wherein ethylene undergoes a reaction at a metal center, resulting in the formation and destruction of covalent bonds. Herein, we describe the advantages and disadvantages of various approaches, and the challenges remaining for sensor development. [ABSTRACT FROM AUTHOR]

Visible light‐driven photocatalysis has gained much attention due to its light‐harnessing characteristics and is extensively used in wastewater remediation. This paper presents a novel oxygen‐deficient manganese antimonate, MnSb2O6‐x, with a trirutile structure as an effective visible‐light‐driven photocatalyst for dye degradation. The synthesized samples were subjected to XRD, UV‐Vis DRS, SEM‐EDS, Raman, XPS, and PL analyses to study their physic chemical properties. The influence of sequential or single heating during the preparation method on the generation of oxygen vacancies is evaluated using UV‐Vis DRS, XPS, ESR, and Raman techniques. The oxygen‐deficient MnSb2O6 could achieve up to 85 % of MO degradation in 180 min under visible light irradiation, and its reusability up to six cycles was also investigated. In addition, the mechanism of dye degradation was supported with a scavenger test, and the degradation activities are correlated to the electron‐hole pair separation as convinced from the PL spectra. The simple and unique method of oxygen vacancy generation can inspire the development of antimonates with oxygen deficiencies, which have significant scope of application in environmental and energy conservation. [ABSTRACT FROM AUTHOR]

2‐Arylpropylamines are useful as active pharmaceutical ingredients (APIs) and as synthetic building blocks in fine chemistry. Herein we report a new and efficient methodology to transform naturally occurring 1‐propenylbenzenes into 2‐arylpropylamines employing a one‐pot ethenolysis/hydroaminomethylation protocol. Four consecutive reactions must occur in the same reaction vessel and the careful selection of the reaction conditions was critical to obtain the desired products in high yields. The negative interference between the ethenolysis and the hydroaminomethylation (HAM) catalysts was circumvented by the appropriate adjustment on the molar ratio of the catalysts. As a result, nine 2‐arylpropylamines were obtained in yields ranging in 75–93 %. [ABSTRACT FROM AUTHOR]

Development of more sustainable and environmentally friendly polymers as alternatives to petroleum‐based polymers is a priority. We report the synthesis of six linear, aliphatic, renewable polymers by acyclic diene metathesis (ADMET) and thiol‐ene polymerization of α,ω‐polyenes resulting from thermal esterification of adipic, azelaic, and itaconic acids with 9‐decen‐1‐ol. ADMET homopolymerization was performed with 1.0 mol% Hoveyda–Grubbs second generation metathesis catalyst. Thiol‐ene copolymerization was conducted photochemically with 1 wt% 2,2‐dimethoxy‐2‐phenyl‐acetophenone and stoichiometric 1,2‐ethanedithiol (EDT). Although the thiol‐ene copolymers exhibited carbon and atom economies of 100%, the ADMET‐derived polyesters possessed superior renewable carbon content (100%) and environmental factors (<4). These results were attributed to incorporation of non‐renewable EDT into poly(thioether‐ester)s and loss of ethene during production of ADMET polyesters. The Mn (>26 kDa), Mw (>92 kDa), and dispersities (>3.4) of the poly(thioether‐ester)s were higher than the corresponding polyesters, which in part explained why the poly(thioether‐ester)s gave higher melting (>61°C), crystallization (>49°C) and glass transition (>−31°C) temperatures. The cross‐linked itaconate polymers did not melt or crystallize, thereby suggesting amorphous morphology. Lastly, the ADMET polyesters were more thermally stable (T50 > 408°C) than the poly(thioether‐ester)s (T50 < 377°C). In summary, the aliphatic biopolymers displayed a wide range of properties that were impacted by polymerization method as well as the nature of the monomer. [ABSTRACT FROM AUTHOR]

A series of molybdenum alkylidyne silyloxy N‐heterocyclic carbene (NHC) complexes of the general formula [Mo(≡C(R))(OSiPh3)3(NHC)] (R=tBu, 4‐methoxyphenyl, 2,4,6‐trimethylphenyl; NHC = 1,3‐diisopropylimidazol‐2‐ylidene, 1,3‐dicyclohexylimidazol‐2‐ylidene, 1,3‐dicyclohexyl‐4,5‐dihydroimidazol‐2‐ylidene, 1,3‐dimethylimidazol‐2‐ylidene, 1,3‐dimethyl‐4,5‐dichloroimidazol‐2‐ylidene) was synthesized. Single crystal X‐ray analyses revealed that with increasing steric demand of the alkylidyne group, enhanced air‐stability of the complexes in the solid‐state is achieved with the most stable complex (R=2,4,6‐trimethylphenyl, NHC = 1,3‐diisopropylimidazol‐2‐ylidene) being stable in air for 24 h without showing signs of decomposition in 1H NMR. In contrast to previously reported air‐stable molybdenum‐based complexes, the novel catalysts proved to be highly active in alkyne metathesis, allowing for turnover numbers (TONs) of up to 6000 without further activation, and tolerant towards several functional groups such as tosyl, ether, ester, thioether and nitro moieties. Their air stability allows for facile handling of the catalysts in air and even after exposure to ambient atmosphere for one week, the most stable representative still displayed high productivity in alkyne metathesis. [ABSTRACT FROM AUTHOR]

The post‐translational modifications (PTMs) on the tail of histone H3 control chromatin structure and influence epigenetics and gene expression. The current chemical methods including unnatural amino acid incorporation and protein splicing enable preparations of the histone with diverse PTMs in cellular contexts, but they are not applicable to edit native chromatin. The manipulation of histone‐modifying enzymes alter the endogenous histone PTMs but the lack of specificity of most histone‐modifying enzymes prevents precise control of specific H3 tail PTM patterns. Here we report a new method to edit the N‐tail of histone H3 via sortase mediated metathesis (SMM). The sortase can install desired PTM patterns into histone H3 on nucleosomes in vitro and in cellulo. This study expands the application scope of sortase from ligation to metathesis in live cells using cell‐penetrating peptides (CPPs). In addition, it offers a strategy to edit PTMs of cellular histone H3 with potential for the development of precise epigenome editing. [ABSTRACT FROM AUTHOR]

Alkene metathesis catalyzed by enantiopure metal alkylidene complexes enables exceptionally versatile strategies to products with configurationally‐defined stereocenters. Desymmetrization processes thereby provide reliable stereoselective routes to aliphatic structures, while the differentiation of aromatic stereogenic units remained an outstanding challenge. Herein, we describe the feasibility of alkene metathesis to catalytically control stereogenic axes by traceless arene formation. Stereodynamic trienes are selectively converted into corresponding binaphthalene atropisomers upon exposure to a chiral molybdenum catalyst. Remarkably, stereoselective arene‐forming metathesis allows enantioselectivities of up to 98 : 2 e.r. and excellent yields. As the disconnection of each bond of an aromatic target is retrosynthetically conceivable, it is anticipated that forging arenes by means of stereoselective metathesis will enable versatile approaches for the synthesis of a broad range of molecular topologies with precisely defined configuration. [ABSTRACT FROM AUTHOR]

Herein, we describe new synthetic approaches to fused 5/5/6‐carbocyclic frameworks present in various polycyclic natural products such as presilphiperfolanols, lycopodium alkaloids, and cyclopiane diterpenes. Our work features, a strategically introduced hydroxy group at the tert‐carbon center of the tricyclic system which is present in presilphiperfolanols. In addition, one presilphiperfolanol analogue is reported to show the potential of strategies disclosed in this work. All the new compounds are characterized by high‐resolution NMR spectral data. The structures of critical compounds were confirmed by various chemical transformations and further supported by single‐crystal X‐ray diffraction data. Overall, our approach is simple and rely on readily available starting materials and involves a tandem‐metathesis sequence. The synthetic studies disclosed here are applicable to the synthesis of natural products and to design medicinally important targets. [ABSTRACT FROM AUTHOR]

The gallium(III) nitridophosphate‐oxide Ga16/3[P12N24]O2 was synthesized by metathesis reaction between GaF3 and LiPN2. The crystal structure was elucidated by electron crystallography and powder X‐ray diffraction, comparing both approaches. This reveals a partially collapsed sodalite‐type structure (space group I4‾ ${\bar{4}}$ 3m, a=8.1585(2) Å) with a tilt angle ϕ of ∼33°. Vertex‐sharing PN4 tetrahedra build up a sodalite network that hosts gallium(III) cations and oxide anions. Gallium forms bonds to further three N atoms. The structure model is confirmed by EDX analyses, IR spectroscopy and bond valence sum calculations. [ABSTRACT FROM AUTHOR]

The synthesis of some novel functionalized azaheterocyclic β‐amino esters with multiple chiral centers via a stereocontrolled synthetic route has been carried out using some cyclooctene β‐amino acids as starting model compounds. The strategy of the method was planned to create some novel unsaturated N‐protected cyclic β‐amino esters that were subjected to ring‐opening metathesis (ROM) followed by selective ring‐closing metathesis (RCM). A number of experimental conditions were accomplished to investigate the activity of catalysts, yields, conversions, and substrate effect on ring‐rearrangement metathesis (RRM) transformation. Importantly, the procedure used in this synthetic process does not affect the configuration of the chiral centers; therefore, the stereochemistry of the starting cyclooctadiene β‐amino acids predetermined the structure of the new azaheterocyclic derivatives. [ABSTRACT FROM AUTHOR]

The light‐driven gem‐hydrogenation of internal alkynes in the presence of [(NHC)(η6‐cymene)RuCl2] generates discrete ruthenium carbene complexes. When applied to appropriately designed enyne substrates, the reactive intermediates thus formed will engage the tethered olefin in metathetic ring closure while splitting off a Hoveyda–Grubbs‐type complex as secondary carbene. This unconventional approach to these classical catalysts for olefin metathesis rivals existing methodology in that it is safe, short, phosphine‐free, and uses readily available starting materials. [ABSTRACT FROM AUTHOR]

A systematic study to access stable stannaimines is reported, by combining different heteroleptic stannylenes with a range of organic azides. The reactions of terphenyl‐/hypersilyl‐substituted stannylenes yield the putative tin nitrogen double bond, but is directly followed by 1,2‐silyl migration to give SnII systems featuring bulky silylamido ligands. By contrast, the transition from a two σ donor ligand set to a mixed σ‐donor/π‐donor scaffold allows access to three new stannaimines which can be handled at room temperature. The reactivity profile of these Sn=N bonded species is crucially dependent on the substituent at the nitrogen atom. As such, the Sn=NMes (Mes=2,4,6‐Me3C6H2) system is capable of activating a broad range of substrates under ambient conditions via 1,2‐addition reactions, [2+2] and [4+2] cycloaddition reactions. Most interestingly, very rare examples of main group multiple bond metathesis reactions are also found to be viable. [ABSTRACT FROM AUTHOR]

In this work an approach for the synthesis of furanocembranoid natural products containing the C‐7,8‐diol moiety is disclosed. This culminated in the first total synthesis of the natural product molestin E, together with ent‐sinulacembranolide A and ent‐sinumaximol A as well as a thorough exploration of their chemistry. Late‐stage ring‐closure of the C‐7,8‐diols to the corresponding epoxides was also demonstrated. Key features of this synthetic strategy include a stereoselective Baylis‐Hillman reaction, ring‐closing metathesis and Shiina macrolactonisation. Chiral‐pool materials were deployed to ensure the desired absolute stereochemistry which was confirmed by late‐stage single crystal X‐ray diffraction. [ABSTRACT FROM AUTHOR]

Cyclopolymerization is a powerful method for synthesizing polyacetylenes containing four‐ to seven‐membered rings. However, the structure of the repeat unit only consists of mono‐cycloalkene due to the single cyclization of diyne monomers. Herein, we demonstrate a novel cascade cyclopolymerization to synthesize polyacetylenes containing fused bicyclic rings from triyne monomers containing bulky dendrons via sequential cascade ring‐closing metathesis. These dendrons provided solubility and stability to the rigid bicyclic polyacetylene backbone. In addition, we controlled the regioselectivity of the catalyst approach by altering its structure and synthesized polymers containing fused bicyclo[4,3,0] or [4,4,0] rings with high molecular weights of up to 120 kg mol−1. Interestingly, the resulting polymers showed narrower band gaps (down to 1.6 eV) than polymers with mono‐cycloalkene repeat units due to the planarization of the conjugated segment resulting from the fused bicyclic structure. [ABSTRACT FROM AUTHOR]

Catalytic enantioselective hydroxylation of prochiral dihydrosilanes with water is expected to be a highly efficient way to access Si‐chiral silanols, yet has remained unknown up to date. Herein, we describe a strategy for realizing this reaction: using an alkyl bromide as a single‐electron transfer (SET) oxidant for invoking CuII species and chiral multidentate anionic N,N,P‐ligands for effective enantiocontrol. The reaction readily provides a broad range of Si‐chiral silanols with high enantioselectivity and excellent functional group compatibility. In addition, we manifest the synthetic potential by establishing two synthetic schemes for transforming the obtained products into Si‐chiral compounds with high structural diversity. Our preliminary mechanistic studies support a mechanism involving SET for recruiting chiral CuII species as the active catalyst and its subsequent σ‐metathesis with dihydrosilanes. [ABSTRACT FROM AUTHOR]

Ionic liquids have recently emerged as monomers to synthesize multifunctional polymeric materials. Among such species, ionic epoxy‐based networks represent promising but underdeveloped materials that are hindered by tricky access to the functionalized ionic liquid monomers. To date, the reported epoxidized imidazolium salts have focused on highly toxic epichlorohydrin. This study concerns flexible and efficient methods to synthesize versatile building blocks with sulfonates as valuable anions. The judicious combination of an aliphatic or aromatic sulfonate with an imidazolium leads to new epoxidized salts with high structural variability and good chemical and thermal stability (>300 °C). [ABSTRACT FROM AUTHOR]

Ruthenium‐mediated olefin metathesis has been widely applied for the synthesis of various organic molecules and polymers. Inspired by the cocatalyst strategy for olefin polymerization, here we demonstrate that the abstraction of a chloride ion from various commercially available ruthenium catalysts significantly enhances their reactivity towards electron‐deficient internal olefins. This cocatalyst strategy can be implemented in ethenolysis and cross‐metathesis reactions of FG‐CH=CH‐FG type substrates bearing electron‐withdrawing groups and the synthesis of telechelic polymers that can be converted to polyethylene‐like materials with closed‐loop recycling properties. The copolymerization of cyclic substrate with cycloolefins followed by hydrogenation afforded polyolefin materials with in‐chain break points. Interestingly, switchable catalysis was achieved in the absence and presence of a cocatalyst, which allowed the polymer microstructure and material properties to be fine‐tuned. [ABSTRACT FROM AUTHOR]