Noteworthy Chemistry

March 30, 2015


Olefin metathesis goes mechanochemical. Olefin metathesis is a powerful tool for forming C=C bonds by exchanging alkylidene fragments between two alkenes. The technique is widely used for synthesizing natural products, pharmaceuticals, polymers, and other chemicals. Olefin metathesis has matured as a common synthetic method in liquid media, but solid-state reactions have not been explored.

T. Friščić and colleagues at McGill University (Montreal) examined various metathesis reactions by using the rapidly developing technique of mechanochemical synthesis. They developed a process for easy, efficient mechanochemical ruthenium-catalyzed olefin metathesis.

The authors first investigated the homometathesis of several simple liquid and solid styrene derivatives by using solvent-free milling and liquid-assisted grinding (LAG) in Teflon milling jars (see figure). (Conventional steel jars might have poisoned ruthenium catalysts by reducing them.) They found that neat-milling liquid olefins rapidly gives high metathesis yields. They identified the second-generation Hoveyda–Grubbs catalyst as the best catalyst. 

Homometathesis of styrene derivatives

With the same process, solid olefins give significantly lower yields, but using LAG with inorganic salt–based solid auxiliaries improves the yields. The method also can be used for the ring-closing metathesis of several terminal dienes. The authors demonstrated that mechanochemical metathesis can be run on a multigram scale.

This process provides a general, scalable mechanochemical route to olefin metathesis with potential industrial applications. It can potentially extend the scope of mechanochemistry to metathesis polymerizations. Because the method uses virtually no solvent, it is a practical addition to green chemistry as well. (J. Am. Chem. Soc. DOI: 10.1021/jacs.5b00151; Xin Su)

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Optimize the route to a pyridine sulfide by tweaking the reactants. In the course of developing a scalable process for making the insecticide Isoclast, D. C. Bland and co-workers at Dow (Midland, MI, and Indianapolis) synthesized a pyridine sulfide intermediate by using a Michael addition followed by cyclization. The enamine, formed from 3-methylthiobutanal, undergoes the addition reaction with a 4-alkoxy-(1,1,1-trifluoro)-2-butenone to form a diene intermediate that cyclizes in the presence of ammonium acetate.

During the optimization of this one-pot sequence, it became apparent that the structure of the amine used for forming the enamine and the alkyl group in the trifluoroacetylvinyl ether has an impact on the success of the process. Cyclic secondary amines perform better than noncyclic secondary amines. Pyrrolidine gives the best results, in line with literature precedent. A screen of C1–4 alkoxy groups in the enone showed that ethoxy and isopropoxy were superior to the others; but the reasons for this were not clear to the authors. (Org. Process Res. Dev. DOI: 10.1021/acs.oprd.5b00007; Will Watson)

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Polymers with unconventional chromophores emit strong blue light. Luminescent macromolecules usually contain chromophores with extended π-electron conjugation, such as in multiple aromatic rings. But in recent decades, some polymers that do not contain conventional chromophores, such as dendritic and hyperbranched poly(amidoamine)s (PAMAMs), have been found to emit efficiently. It has been suggested that oxidized aliphatic tertiary amines play a key role in the luminescence of PAMAMs.

Now, H. Lu, S. Feng, and co-workers at Shandong University (Jinan, China) report a series of dendritic siloxane–containing PAMAMs (Si-PAMAMs) that although not oxidized, are highly fluorescent.

The researchers synthesized the Si-PAMAM dendrimers (see figure) in high yields by using alternating aza-Michael and amidation reactions. The dendrimers emit strong blue light in the absence of an oxidizing reagent, whereas their counterparts without siloxane units are almost nonfluorescent. 

Aggregation-enhanced emission of Si-PAMAM polymers

The fluorescence intensity of Si-PAMAMs increases rapidly with an increase in the generation number of the dendrimer. The dendrimers exhibit aggregation-enhanced emission in water–methanol systems.

The authors’ mechanism study suggests that the N–Si coordination bond in Si-PAMAMs facilitates aggregate formation. It also indicates that aggregation of the carbonyl groups is responsible for the strong light emission from these unconventional luminogen systems. (Macromolecules DOI: 10.1021/ma502352x; Ben Zhong Tang)

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The fire is over, but the fire retardants linger on. Legal and regulatory restrictions have been successful in reducing the use of polybrominated diphenyl ether (PBDE) flame retardants, polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs). These compounds, however, degrade very slowly in the environment, and older products manufactured from these compounds remain in use. PCBs and some PBDEs have been associated with various disruptions in human and animal physiological processes. Combustion products of PBDEs, including dioxins and furans, may be more toxic than the parent compounds.

J.-S. Park, R. W. Voss, and coauthors at the California Environmental Protection Agency (Berkeley), the California Department of Public Health (Richmond), the Sequoia Foundation (La Jolla, CA), and the University of California, Irvine, examined serum concentrations of PBDEs, PCBs, and OCPs for 101 southern California firefighters as part of the California Environmental Contaminant Biomonitoring Program. They collected detailed information about the participants' physiology, firefighting history, and gear maintenance and storage practices. They compared their results to those from other occupationally exposed groups (e.g., waste workers and foam-factory workers) and to less-exposed populations.

Firefighters exhibited high serum levels of PBDEs, in contrast to declining levels for Californians overall. Firefighters' levels of PCBs and OCPs were in line with nationwide levels. Multivariate analysis indicated that firefighters could reduce their serum levels of PCBs and OCPs (but not PBDEs) by having their turnout gear (trousers, jackets, boots, and helmets) professionally decontaminated after a fire.

The levels of some BDEs could be lowered by storing turnout gear in an open room rather than in enclosed lockers and by cleaning gear at the fire station rather than at the response site. Other factors included the use of self-contained breathing apparatuses during firefighting activities (regardless of whether the fire was inside or outside a structure) and the age of the fire station. (Environ. Sci. Technol. DOI: 10.1021/es5055918; Nancy McGuire)

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Teixobactin kills drug-resistant strains of Gram-positive bacteria. Antibiotic resistance is a major problem in modern medicine, yet new antimicrobials are difficult to find. A potential source of powerful antibiotics is “uncultured” bacteria that are unable to grow under lab conditions. K. Lewis and collaborators at NovoBiotic Pharmaceuticals (Cambridge, MA), the University of Bonn (Germany), the German Center for Infection Research (DZIF) (Bonn), Northeastern University (Boston), and Selcia (Essex, UK) had previously developed methods for isolating and growing these organisms in their natural environment.

Lewis and her team tested extracts from 10,000 uncultured isolates for antimicrobial activity against Staphylococcus aureus. They isolated an active compound from a new species of β-proteobacteria that they provisionally named Eleftheria terrae. This molecule, teixobactin (1), is a depsipeptide with enduracididine, methylphenylalanine, and four D-amino acid components (see figure).

Structure of teixobactin

Teixobactin functions by inhibiting bacterial cell-wall synthesis. It targets the surface-exposed peptidoglycan precursor, lipid II, and the cell-wall teichoic acid precursor, lipid III, by binding the pyrophosphate-sugar moiety on polyprenyl-coupled cell envelope precursors.

Teixobactin is active against Gram-positive pathogens such as Mycobacterium tuberculosis, Clostridium difficile, Bacillus anthracis, and, notably, drug-resistant strains of S. aureus and Streptococcus pneumoniae. Methicillin-resistant S. aureus usually kills at least 90% of infected mice, yet 100% of mice treated with teixobactin at1 h postinfection survived.

Teixobactin is the first member of a new class of antibiotics. It is stable and effective; and it shows no toxicity against mammalian cells. Moreover, the authors were unable to select for teixobactin-resistant mutants of S. aureus or M. tuberculosis, which suggests that it will take a long time for a resistance mechanism to emerge naturally. (Nature DOI: 10.1038/nature14098; Abigail Druck Shudofsky)

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Catch the moment of carbon monoxide oxidation on ruthenium. The transition state of a chemical reaction is an intermediate structure between reactants and products that defines the activation energy required for the reaction. Transition states are critical to understanding chemical reactivity, but identifying them is usually elusive because of their ultrashort lifetimes.

Now, by using femtosecond X-ray techniques, A. Nilsson at the SLAC National Accelerator Laboratory (Menlo Park, CA) and colleagues in California, Sweden, Germany, and the United Kingdom observed the transient transition state for the oxidation of CO on the surface of ruthenium. The study also revealed ruthenium’s unique electronic states throughout the reaction.

The authors first excited CO and oxygen species adsorbed on ruthenium by using an optical laser pump pulse, which provided enough energy to initiate the reaction between the two reactants. They monitored the process with ultrafast pump-probe X-ray spectroscopy with femtosecond resolution. Within a picosecond, they observed new signals in the K-edge X-ray absorption spectrum for oxygen that indicated the generation of new electronic states. Subsequent quantitative data on bond formation and kinetics were consistent with computational predictions.

This study is the first time that short-lived intermediates closely related to transition-state species have been experimentally characterized. This reliable method for validating and calibrating theoretical calculations on heterogeneous catalysis is a powerful tool for studying chemical reactions and surface reactivities. (Science DOI:10.1126/science.1261747; Xin Su)

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