Syntheses of Tungsten Imido Cyclohexylidene Complexes Using Perfluoro-t-Butanol or Hexafluoro-t-Butanol as Acids.

The fluorinated alcohols, (CF)COH (ROH) and (CF)MeCOH (ROH), react with W(NR)Cy (Cy=Cyclohexyl; R=2,6-diisopropylphenyl or 1-adamantyl) in CD at 55 °C to give cyclohexylidene complexes. Traditional routes to terminal alkylidene complexes (neopentylidene or neophylidene) have used either triflic acid or HCl (rarely), but relatively weak fluorinated acids are sufficient and active bisalkoxide catalysts are therefore prepared directly. An α hydrogen abstraction reaction to give a cyclohexylidene complex from a biscyclohexyl complex appears to be as facile as α hydrogen abstraction to give a neopentylidene or neophylidene ligand, but isomerization of a cyclohexene formed through β hydrogen abstraction is also a possibility.

Thermal Formation of Metathesis-Active Tungsten Alkylidene Complexes from Cyclohexene.

A 7-tungstabicyclo[4.3.0]nonane complex forms slowly upon addition of cyclohexene to the ethylene complex, W(NAr)(OSiPh)(CH), at 22 °C.

Improvement of Precision in Recombinant Adeno-Associated Virus Infectious Titer Assay with Droplet Digital PCR as an Endpoint Measurement.

Recombinant adeno-associated virus (rAAV) has been utilized successfully for gene delivery for treatment of a variety of human diseases. To sustain the growth of recombinant AAV gene therapy products, there is a critical need for the development of accurate and robust analytical methods. Fifty percent tissue culture infectious dose (TCID) assay is an cell-based method widely used to determine AAV infectivity, and this assay is historically viewed as a challenge due to its high variability.

Ring Contraction of a Tungstacyclopentane Supported on Silica: Direct Conversion of Ethylene to Propylene.

The reaction of W(NAr)(CH)(OSiPh) () (NAr = 2,6-diisopropylphenylimido) with silica partially dehydroxylated at 700 °C (SiO) is highly dependent on the reaction conditions. The primary product of this reaction is W(NAr)(CH)(OSiPh)(OSi(O-)) () when the reaction is carried out in the dark. Grafting onto SiO in ambient lab light results in the formation of , W(NAr)(CHCH)(OSiPh)(OSi(O-)) (), and one isomer of square-pyramidal W(NAr)(CHCH(Me)CH)(OSiPh)(OSi(O-)) ().

Tungstacyclopentane Ring Contraction Yields Olefin Metathesis Catalysts.

Exposure of a solution of the square pyramidal tungstacyclopentane complex W(NAr)(OSiPh)(CH) (Ar = 2,6--PrCH) to ethylene at 22 °C in ambient (fluorescent) light slowly leads to the formation of propylene and the square pyramidal tungstacyclobutane complex W(NAr)(OSiPh)(CH). No reaction takes place in the dark, but the reaction is >90% complete in ∼15 min under blue LED light (∼450 nm λ). The intermediates are proposed to be (first) an α methyl tungstacyclobutane complex (W(NAr)(OSiPh)(αMeCH)), and then from it, a β methyl version.

E- and Z-trisubstituted macrocyclic alkenes for natural product synthesis and skeletal editing.

Many therapeutic agents are macrocyclic trisubstituted alkenes but preparation of these structures is typically inefficient and non-selective. A possible solution would entail catalytic macrocyclic ring-closing metathesis, but these transformations require high catalyst loading, conformationally rigid precursors and are often low yielding and/or non-stereoselective. Here we introduce a ring-closing metathesis strategy for synthesis of trisubstituted macrocyclic olefins in either stereoisomeric form, regardless of the level of entropic assistance.

Stereodefined alkenes with a fluoro-chloro terminus as a uniquely enabling compound class.

Trisubstituted alkenyl fluorides are important compounds for drug discovery, agrochemical development and materials science. Despite notable progress, however, many stereochemically defined trisubstituted fluoroalkenes either cannot be prepared efficiently or can only be accessed in one isomeric form. Here we outline a general solution to this problem by first unveiling a practical, widely applicable and catalytic strategy for stereodivergent synthesis of olefins bearing a fluoro-chloro terminus.

Interconversion of Molybdenum or Tungsten d Styrene Complexes with d 1-Phenethylidene Analogues.

Upon addition of 5-15% PhNMeHX (X = B(3,5-(CF)CH) or B(CF)) to Mo(NAr)(styrene)(OSiPh) (Ar = N-2,6--PrCH) in CD an equilibrium mixture of Mo(NAr)(styrene)(OSiPh) and Mo(NAr)(CMePh)(OSiPh) is formed over 36 h at 45 °C ( = 0.36). A plausible intermediate in the interconversion of the styrene and 1-phenethylidene complexes is the 1-phenethyl cation, [Mo(NAr)(CHMePh)(OSiPh)], which can be generated using [(EtO)H][B(CF)] as the acid.

Stereochemical Control Yields Mucin Mimetic Polymers.

All animals except sponges produce mucus. Across the animal kingdom, this hydrogel mediates surface wetting, viscosity, and protection against microbes. The primary components of mucus hydrogels are mucins-high molecular weight -glycoproteins that adopt extended linear structures.

Boosting the Metathesis Activity of Molybdenum Oxo Alkylidenes by Tuning the Anionic Ligand σ Donation.

The catalytic performances of molecular and silica-supported molybdenum oxo alkylidene species bearing anionic O ligands [OR, OTPP, OHMT - where OR = OC(CF), OTPP = 2,3,5,6-tetraphenylphenoxy, OHMT = hexamethylterphenoxy] with different σ-donation abilities and sizes are evaluated in the metathesis of both internal and terminal olefins. Here, we show that the presence of the anionic nonafluoro--butoxy X ligand in Mo(O){═CH-4-(MeO)CH}(THF){X} (; X = OR) significantly increases the catalytic performances in the metathesis of both terminal and internal olefins. Its silica-supported equivalent displays slightly lower activity, albeit with improved stability.

Silica-Supported Molybdenum Oxo Alkylidenes: Bridging the Gap between Internal and Terminal Olefin Metathesis.

Grafting a molybdenum oxo alkylidene on silica (partially dehydroxylated at 700 °C) affords the first example of a well-defined silica-supported Mo oxo alkylidene, which is an analogue of the putative active sites in heterogeneous Mo-based metathesis catalysts. In contrast to its tungsten analogue, which shows poor activity towards terminal olefins because of the formation of a stable off-cycle metallacyclobutane intermediate, the Mo catalyst shows high metathesis activity for both terminal and internal olefins that is consistent with the lower stability of Mo metallacyclobutane intermediates. This Mo oxo metathesis catalyst also outperforms its corresponding neutral silica-supported Mo and W imido analogues.

E- and Z-, di- and tri-substituted alkenyl nitriles through catalytic cross-metathesis.

Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for the preparation of di- or tri-substituted alkenyl nitriles. Related approaches that are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce.

Protonation Studies of Molybdenum(VI) Nitride Complexes That Contain the [2,6-(ArNCH)NCH] Ligand (Ar = 2,6-Diisopropylphenyl).

[ArN]Mo(N)(O- t-Bu) (1), which contains the conformationally rigid pyridine-based diamido ligand [2,6-(ArNCH)NCH] (Ar = 2,6-diisopropylphenyl), is a catalyst for the reduction of dinitrogen with protons and electrons. Various acids have been added in order to explore where and how the first proton adds to the complex. The addition of adamantol to 1 produces a five-coordinate bis(adamantoxide), [HArN]Mo(N)(OAd) (2a), in which one of the amido nitrogens in the ligand has been protonated and the resulting aniline nitrogen in the [HArN] ligand is not bound to the metal.

Traceless Protection for More Broadly Applicable Olefin Metathesis.

An operationally simple in situ protection/deprotection strategy that significantly expands the scope of kinetically controlled catalytic Z- and E-selective olefin metathesis is introduced. Prior to the addition of a sensitive Mo- or Ru-based complex, treatment of a hydroxy- or a carboxylic-acid-containing olefin with commercially available HB(pin) or readily accessible HB(trip) (pin=pinacolato, trip=2,4,6-tri(isopropyl)phenyl) for 15 min is sufficient for efficient generation of a desired product. Routine workup leads to quantitative deprotection.

Synthesis of High-Oxidation-State Mo═CHX Complexes, Where X = Cl, CF, Phosphonium, CN.

Reactions between -XCH=CHX where X = Cl, CF, or CN and Mo(N--Bu)(CH--Bu)(OHIPT)Cl(PPhMe) (OHIPT = O-2,6-(2,4,6--PrCH)CH) produce Mo(N--Bu)(CHX)(OHIPT)Cl(PPhMe) complexes. Addition of 2,2'-bipyridyl (Bipy) yields Mo(N--Bu)(CHX)(OHIPT)Cl(Bipy) complexes, which could be isolated and structurally characterized. The reaction between Mo(N--Bu)(CH--Bu)(OHMT)Cl(PPhMe) (OHMT = O-2,6-(2,4,6-MeCH)CH) and -ClCH=CHCl in the presence of Bipy produces a mixture that contains both Mo(N--Bu)(CHCl)(OHMT)Cl(PPhMe) and Mo(N--Bu)(CHCl)(OHMT)Cl(Bipy), but the relatively insoluble product that crystallizes from toluene- is the phosphoniomethylidene complex, [Mo(N--Bu)(CHPPhMe)(OHMT)(Cl)(Bipy)]Cl.

Molybdenum Complexes that Contain a Calix[6]azacryptand Ligand as Catalysts for Reduction of N to Ammonia.

[CAC(OMe)]Mo(N) (3, where [CAC] is a calix[6]azacryptand ligand derived from a [6]calixarene) has been prepared in a reaction between Li[CAC(OMe)] and ( t-BuO)Mo(N). An X-ray structural study showed 3 to have a structure similar to that of [HIPTNN]Mo(N) (where [HIPTNN] is [(3,5-(2,4,6-triisopropylphenyl)CHNCHCH)N]). The relatively rigid [CAC(OMe)] ligand in 3 forms a bowl-shaped cavity defined by a 24-atom macrocyclic ring.

Syntheses of Molybdenum Oxo Benzylidene Complexes.

The reaction between Mo(O)(CHAr)(OR)(PMe) (Ar = ortho-methoxyphenyl, OR = OCMe(CF)) and 2 equiv of LiOHMT (OHMT = O-2,6-(2,4,6-MeCH)CH) leads to Mo(O)(CHAr)(OHMT), an X-ray structure of which shows it to be a trigonal bipyramidal anti benzylidene complex in which the o-methoxy oxygen is coordinated to the metal trans to the apical oxo ligand. Addition of 1 equiv of water (in THF) to the benzylidyne complex, Mo(CAr)(OR)(THF) (Ar = para-methoxyphenyl, OR = OR or OC(CF) (OR)) leads to formation of {Mo(CAr)(OR)(μ-OH)(THF)}(μ-THF) complexes. Addition of 1 equiv of a phosphine (L) to Mo(CAr)(OR)(THF) in THF, followed by addition of 1 equiv of water, all at room temperature, yields Mo(O)(CHAr)(OR)(L) complexes in good yields for several phosphines (e.

Beyond fossil fuel-driven nitrogen transformations.

Nitrogen is fundamental to all of life and many industrial processes. The interchange of nitrogen oxidation states in the industrial production of ammonia, nitric acid, and other commodity chemicals is largely powered by fossil fuels. A key goal of contemporary research in the field of nitrogen chemistry is to minimize the use of fossil fuels by developing more efficient heterogeneous, homogeneous, photo-, and electrocatalytic processes or by adapting the enzymatic processes underlying the natural nitrogen cycle.

Syntheses of Molybdenum Oxo Alkylidene Complexes through Addition of Water to an Alkylidyne Complex.

Addition of one equiv of water to Mo(CAr)[OCMe(CF)](1,2-dimethoxyethane) (2, Ar = o-(OMe)CH) in the presence of PPhMe leads to formation of Mo(O)(CHAr)[OCMe(CF)](PPhMe) (3(PPhMe)) in 34% yield. Addition of one equiv of water alone to 2 produces the dimeric alkylidyne hydroxide complex, {Mo(CAr)[OCMe(CF)](μ-OH)}(dme) (4(dme)) in which each bridging hydroxide proton points toward an oxygen atom in an arylmethoxy group. Addition of PMe to 4(dme) gives the alkylidene oxo complex, (3(PMe)), an analogue of 3(PPhMe) (95% conversion, 66% isolated).

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis.

Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity-namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products-and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem.

Reduction of Dinitrogen to Ammonia Catalyzed by Molybdenum Diamido Complexes.

[ArN]Mo(N)(O-t-Bu), which contains the conformationally rigid pyridine-based diamido ligand, [2,6-(ArNCH)NCH] (Ar = 2,6-diisopropylphenyl), can be prepared from H[ArN], butyllithium, and (t-BuO)Mo(N). [ArN]Mo(N)(O-t-Bu) serves as a catalyst or precursor for the catalytic reduction of molecular nitrogen to ammonia in diethyl ether between -78 and 22 °C in a batchwise manner with CoCp* as the electron source and PhNHOTf as the proton source. Up to ∼10 equiv of ammonia can be formed per Mo with a maximum efficiency in electrons of ∼43%.

[Effects of a Phone-Based Follow-Up Care After Inpatient Rehabilitation for Breast Cancer Patients - A Randomized Controlled Trial].

Benefit and long-term effects of rehabilitation and psychoeducational interventions after cancer therapy are still controversial discussed. Aim of the study was to evaluate feasibility and effects of a telephone-based follow-up intervention after oncological rehabilitation. 172 breast cancer patients (age 27-54 years) were randomized after inpatient rehabilitation to a telephone-based intervention (phone calls every 4 weeks over 6 months) or control group.

EPR/ENDOR and Theoretical Study of the Jahn-Teller-Active [HIPTNN]MoL Complexes (L = N, NH).

The molybdenum trisamidoamine (TAA) complex [Mo] {[3,5-(2,4,6-i-PrCH)CHNCHCHN]Mo} carries out catalytic reduction of N to ammonia (NH) by protons and electrons at room temperature. A key intermediate in the proposed [Mo] nitrogen reduction cycle is nitridomolybdenum(VI), [Mo(VI)]N. The addition of [e/H] to [Mo(VI)]N to generate [Mo(V)]NH might, in principle, follow one of three possible pathways: direct proton-coupled electron transfer; H first and then e; e and then H.