Noteworthy Chemistry

November 7, 2011

Use a hypervalent bromine oxidant to make aziridines. Hypervalent organo-λ3-iodanes are powerful, environmentally friendly oxidants for a variety of functional groups. M. Ochiai and coauthors at the University of Tokushima (Japan) and the Rigaku Corp. (Tokyo) describe a bromine variant, p-fluoromethyl(diacetoxybromo)benzene (2).

They synthesized 2 by treating p-trifluoromethylphenyl(difluoro)-λ3-bromane (1) with AcOH. The double ligand exchange of the fluorine atoms in 1 with acetoxy groups occurs rapidly under mild conditions to form the desired oxidizing reagent 2 as a crystalline solid in 90% yield. Compound 2 is somewhat air-sensitive, but it can be stored in an inert environment for >2 months with no decomposition.

The authors converted reagent 2 to a trifluoromethanesulfonyl (Tf) intermediate, which was then treated with an internal or terminal olefin in the same pot to form an N-protected aziridine such as 3. The reaction is completely stereospecific and retains the stereochemistry of (Z)- and (E)-olefins. The reaction proceeds smoothly at 0 °C or room temperature without the need for transition-metal catalysis.

The aziridine nitrogen atom can be reductively deprotected under mild conditions to give the corresponding free aziridine 4 as the cis isomer in high yield. This transformation is carried out without forming ring-opened byproducts or isomerizing to the trans isomer. (Org. Lett. 2011, 13, 5428–5431; W. Jerry Patterson)

Carbon dioxide shifts the fluorescence of a host–guest complex. A few chemosensory systems detect trace amounts of gases in the atmosphere by measuring the luminescence generated by chemical reactions of the gases. It is desirable to devise a luminescence-based gas-detection system that responds to weaker interactions such as physical adsorption.

T. Uemura, S. Kitagawa, and coauthors at Kyoto University, the Japan Science and Technology Agency (Kyoto), Osaka Prefecture University, RIKEN SPring-8 Center and CREST (Hyogo), and Kanazawa University (all in Japan) produced a host–guest system that accomplishes this goal. They used a composite of a flexible porous coordination polymer (the host) and the fluorescent reporter molecule distyrylbenzene {DSB; formally 1,4-bis[(E)-2-phenylethenyl]benzene} (the guest).

DSB adsorbs CO2 selectively to other atmospheric gases. The adsorption induces a host transformation accompanied by conformational variations of the guest DSB. These changes significantly alter the DSB fluorescence wavelength and intensity at a specific threshold pressure. For the first time, a fluorescent probe can detect a gas without chemical interaction or energy transfer. (Nat. Mater. 2011, 10, 787–793; Ben Zhong Tang)

Use deuterium NMR to evaluate Lewis acidity. Lewis acids have numerous applications in organic chemistry. Several methods are available for evaluating Lewis acidity, for example, NMR shifts of 1H and other nuclei. G. Hilt and co-workers at Philipps University Marburg (Germany) report a Lewis acidity scale based on 2H NMR.

Their technique relies on 2H NMR shift differences when a Lewis acid is added to a solution that contains a deuterated quinolizidine probe (1). One advantage of using 2H NMR is that there is no interference between the probe and the Lewis acid because only the probe contains deuterium.

The authors tested several boron, aluminum, titanium, and zinc Lewis acids; 10 equiv of each acid was used so that adduct formation was complete. The order of Lewis acid strengths obtained with this technique agreed with traditional empirical and semiquantitative strength scales. In all cases, the 2H shift of the adduct was greater than that of the free amine (1.56 ppm).

The authors also used their method to study the effect of several Lewis acids in Diels–Alder and Povarov reactions. In both reactions, the chemical shift differences were compared with reaction rates measured by UV spectroscopy. The results showed that the order of activity correlates with rate constants; but there were exceptions such as titanium catalysts, for which the NMR method failed to model reactivity. The authors attribute the lack of correlation to the tendency of the catalysts to adopt tetrahedral or octahedral coordination spheres instead of pentacoordinated Lewis acid adducts.

The quantification of Lewis acid strengths obtained with 2H NMR can be used to design asymmetrically catalyzed reactions in which imine or carbonyl groups are activated by the acids. (Eur. J. Org. Chem. 2011, 28, 5962–5966, JosÉ C. Barros)

The nitrogen flow rate affects a chlorination reaction. In the course of developing a large-scale synthesis of a toll-like receptor agonist, G. Bish, P. B. Hodgson, and coauthors at Pfizer (Sandwich, UK) and SRG (London) used PhPOCl2 to convert a hydroxypyridone intermediate to the corresponding chloropyridone. The reaction stalled, however, when the chlorination step was scaled up to 1-L glassware.

The authors tested several hypotheses to find the cause of the problem, including variations in the mode of addition and agitation rate. The difficulty, however, turned out to be the nitrogen flow rate across the reaction. At high flow rates, the reaction stalled; but at low flow, the reaction proceeded to completion. The authors believe that a critical concentration of HCl in the reaction mixture is required for the chlorination to proceed. A high flow of nitrogen across the reaction removes HCl from the system and stops the reaction. (Org. Process Res. Dev. 2011, 15, 788–796; Will Watson)

Detect single DNA molecules. Single-molecule detection is the ultimate “art form” in analytical chemistry. It can elicit information on the behavior of individual molecules and may profoundly change our understanding of macroscale behavior. Single-molecule detection is impeded by such factors as inadequate instrument sensitivity, significant noise levels, and high cost. S. Huang* and Y. Chen* at the University of California, Los Angeles, designed a method to detect individual DNA molecules with the assistance of traditional spectroscopy.

The authors built a polymeric sequence probe (PSP) that consists of a single-stranded DNA molecule with multiple repeat units, each of which contains two components. One binds with the targeted DNA molecule, and the other is a fluorescent dye label. The probe is generated by rolling circle amplification (RCA), which continuously forms the single-stranded units. As the units are repeated, intermolecular interaction causes the probe to attack the targeted DNA strand (A in the figure).

The final complex is soluble in water, and the bound target associates with fluorescent markers (B in the figure). Because of the repeated photosensitive units in the chain, the signal intensity is magnified and noise level is almost nonexistent. The authors used their method to detect Mycobacterium tuberculosis DNA. (Anal. Chem. 2011, 83, 7250−7254; Sally Peng Li)

Chains and scrolls give new insights into nanopeapod structures. Y. Yao, G. S. Chaubey, and J. B. Wiley* at the University of New Orleans developed a processing strategy for creating “peapod” nanostructures. The authors used a multistep method in which K4Nb6O17 is exfoliated to form nanosheets; nanoparticle surface group and scroll formation promoters are added; and cobalt nanoparticles are formed within the layered structures by decomposing Co2(CO)8.

The authors used temperature changes to tune the nanoparticle size distribution: Narrower distributions (most particles in the 10–20-nm range) were obtained at higher temperatures (140–150 °C). They used centrifugation and magnetic separation to isolate multiwalled and single-walled peapod structures that varied in length and the number of ≥10–nm-diam nanoparticles.

The multiwalled peapods exhibited more rigid profiles and uniform diameters, whereas the single-walled nanostructure had undulating profiles. The authors believe that the magnetic alignment of cobalt nanoparticles with ≥8 nm diam is essential to the peapod organization. They propose a mechanism for the nanostructure formation based on image analysis:

  1. chain alignment of the cobalt nanoparticles on the exfoliated niobate layers;
  2. asymmetric scrolling of the layers; and
  3. detachment of the peapods from the layered surface.

(J. Am. Chem. Soc. 2011, 133, Article ASAP DOI: 10.1021/ja206237v; LaShanda Korley)

Steric crowding induces bright fluorescence in boron-based dyes. The family of boron–dipyrromethene (BODIPY) dyes produces significant fluorescence and has diverse potential applications such as artificial light harvesters, solar-cell sensitizers, fluorescent sensors, and laser dyes. This diversity results in part from the introduction of substituents at all positions of the BODIPY scaffold.

V. Lakshmi and M. Ravikanth* at the Indian Institute of Technology Bombay (Mumbai) studied the polyarylation of the BODIPY core to produce dye structures with substituents on each of the aryl rings. This structural arrangement, however, is predicated on the initial preparation of triarylpyrroles, which are difficult to synthesize. The authors report a short, rapid procedure that leads to functionalized polyarylated BODIPYs 14 shown in the figure.

The authors selected meso-anisyldipyrromethane (5) as their starting compound; it is prepared by condensing p-anisaldehyde with excess pyrrole. Compound 5 is brominated with N-bromosuccinimide to yield hexabromo derivative 6 as the sole product. Subsequent oxidation of 6, then treatment with BF3 in a two-step, one-pot reaction, produces BODIPY scaffold 7 in the form of a nonfluorescent green powder. (DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.) Coupling 7 with an arylboronic acid creates the target polyarylated structures 14, with a range of substituents on the phenyl rings.

Compounds 14 are stable fluorescent solids that are readily soluble in common organic solvents. All of the products are strongly fluorescent and form brightly fluorescent red solutions. X-ray crystallography of 1 shows a distorted propeller-like conformation, in contrast with 6, in which the indacene planes are coplanar. The authors suggest that the distorted structure of 1 is caused by the six phenyl rings on the BODIPY core.

Electrochemical studies revealed reversible oxidation and reduction waves for these dyes; photophysical data showed large red shifts in the absorption and emission bands. The results of these studies are consistent with appreciable quantum yields and increased lifetimes compared with unsubstituted BODIPYs. (J. Org. Chem. 2011, 76, 8466–8471: W. Jerry Patterson)

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