Rational Development of Remote C−H Functionalization of Biphenyl: Experimental and Computational Studies

A simple and efficient nitrile-directed meta-C−H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of installing a complex U-shaped template to achieve a molecular U-turn and assemble the large-sized cyclophane transition state for the remote C−H activation, a synthetically useful phenyl nitrile functional group could also direct remote meta-C−H activation. This reaction provides a useful method for the modification of biaryl compounds because the nitrile group can be readily converted to amines, acids, amides, or other heterocycles. Notably, the remote meta-selectivity of biphenylnitriles could not be expected from previous results with a macrocyclophane nitrile template. DFT computational studies show that a ligand-containing Pd–Ag heterodimeric transition state (TS) favors the desired remote meta-selectivity. Control experiments demonstrate the directing effect of the nitrile group and exclude the possibility of non-directed meta-C−H activation. Substituted 2-pyridone ligands were found to be key in assisting the cleavage of the meta-C−H bond in the concerted metalation–deprotonation (CMD) process.     

Coupling of a multilevel fast multipole method and a microlocal discretization for the 3-D integral equations of electromagnetism

The aim of this work is to propose an accurate and efficient numerical approximation for high frequency diffraction of electromagnetic waves. In the context of the boundary integral equations presented in F. Collino and B. Després, to be published in J. Comput. Appl. Math., the strategy we propose combines the microlocal discretization (T. Abboud et al., in: Third International Conference on Mathematical Aspects of Wave Propagation Phenomena, SIAM, 1995, pp. 178–187) and the multilevel fast multipole method (J.M. Song, W.C. Chew, Microw. Opt. Tech. Lett. 10 (1) (1995) 14–19). This leads to a numerical method with a reduced complexity, of order O(N^4/3ln(N)+N_iterN^2/3), instead of the complexity O(N_iterN²) for a classical numerical iterative solution of integral equations. Computations on an academic geometry show that the new method improves the efficiency, for a solution with a good level of accuracy. To cite this article: A. Bachelot et al., C. R. Acad. Sci. Paris, Ser. I 336 (2003).     

Real-time airborne radiation analysis and collection (RTARAC) searching for airborne species characteristic to nuclear proliferation

An effective means of detecting airborne radioactive aerosol plumes has been developed and tested on aircraft platforms. The Real-Time Airborne Radiation Analysis and Collection (RTARAC) system was mounted in the wing pod of a Navy P-3 where it sampled 20 cubic meters of air per minute on each of eleven sequentially advanced filters. A 140% intrinsic gemanium detector counted radioactive particles collected on the 15 cm circular filters in real-time. Gamma-energy spectrum and near real-time analysis of the sample were displayed on a laptop computer.     

Contemplating Criteria for Science Education Reform: The Case of the Olympia School District

Proposals for current reform in science education elaborate national standards and a plethora of state-level interpretations commonly labeled as curriculum or learning frameworks. The purpose of this case study was to examine the dynamics of the science curriculum reform process in one of the first school districts to use the Georgia Framework for Learning Mathematics and Science as a basis for their reform initiative. The paper describes the ways in which members of the Olympia School District's Science Curriculum Committee participated in the science curriculum reform process, as well as their personal beliefs about the criteria needed for reform to take place. The results highlight the nature of metaphors guiding reform efforts; the influence of social, historical, economic, and political forces on the reform process; the use of local and professional languages as discourses for communicating about reform; and the complex power relations that influence the micropolitics of reform in the Olympia School District. This study has important implications for other teachers and school districts engaged in standards-based science curriculum reform. It points to the need for reform to include reflection and analysis of the role of teachers in the reform process and consideration of the purpose of science education reform in society.     

Intramolecular dimers: a new design strategy for fluorescence-quenched probes

Fluorogenic probes dual-labeled with reporter and quencher dyes use a change in fluorescence to monitor biochemical events (e.g., substrate binding or enzyme digestion). Such events change the reporter-quencher distance, which affects fluorescence. Recently, it is has been shown that static quenching through intramolecular dimers is an important mechanism that can sometimes be more efficient than F?rster resonance energy transfer (FRET).     

A Mets motif peptide found in copper transport proteins selectively binds Cu(I) with methionine-only coordination

Mets motifs, which refer to methionine-rich sequences found in the high-affinity copper transporter Ctr1, also appear in other proteins involved in copper trafficking and homeostasis, including other Ctrs as well as Pco and Cop proteins isolated from copper-resistant bacteria. To understand the coordination chemistry utilized by these proteins, we studied the copper binding properties of a peptide labeled Mets7-PcoC with the sequence Met-Thr-Gly-Met-Lys-Gly-Met-Ser. By comparing this sequence to a series of mutants containing noncoordinating norleucine in place of methionine, we confirm that all three methionine residues are involved in a thioether-only binding site that is selective for Cu(I). Two independent methods, one based on mass spectrometry and one based on rate differences for the copper-catalyzed oxidation of ascorbic acid, provide an effective K(D) of approximately 2.5 microM at pH 4.5 for the 1:1 complex of Mets7-PcoC with Cu(I). These results establish that a relatively simple peptide containing an MX(2)MX(2)M motif is sufficient to bind Cu(I) with an affinity that corresponds well with its proposed biological function of extracellular copper acquisition.     

Suzuki-Miyaura cross-coupling of aryl and alkyl halides using palladium/imidazolium salt protocols

A simple new protocol for the high yielding Suzuki-Miyaura cross-couplings of aryl chlorides with aryl boronic acids using a palladium/imidazolium salt catalytic system is presented. The first examples of a palladium/imidazolium salt protocol for sp³-sp³ Suzuki-Miyaura couplings of alkyl halides are also disclosed.     

Quinazolines. VII. Synthesis of 1,3-Diamino-5,6-dihydrobenzo[f]quinazolines

Eighteen new 1,3-diamino-5,6-dihydrobenzo[f] quinazolines ( 6 , R. = alkyl, Cl, MeO) were synthesized via the condensation of appropriate 2-tetralones with cyanoguanidine under fusion conditions. Methods were developed for the preparation of a number of heretofore undescribed 2-tetralones as precursors. The final products can be viewed as conformationally rigid analogs of pyrimethamine ( 2 ), and are of interest as inhibitors of dihydrofolate reductase and as potential antimalarial and antitumor agents.     

Synthesis of the ABC ring system of manzamine A

A synthesis of the core ABC ring system of the manzamine alkaloids is described, starting from arecoline. The key steps involve a Claisen rearrangement to set up a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which undergoes an intramolecular cycloaddition reaction to set up two new rings and three new chiral centers stereoselectively. The aldehyde 6 was not a suitable substrate for related azomethine ylide cycloaddition reactions with other amines. However, the related dimethyl acetal 26 could be condensed with a variety of amines to give the desired tricyclic products. The cycloaddition reaction with N-methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct, whereas cycloaddition with glycine ethyl ester gave the endo adduct.     

Quantum chemical modeling for 157 nm photolithography

In its continuing quest for smaller length scales, the electronics industry plans to introduce 157 nm as the next lithographic wavelength. Accordingly, there is a pressing need to develop photoresists that are more transparent, and pellicles that are both more transparent and more durable. With the advent and popularization of time-dependent density functional theory (TD-DFT), we now have a practical quantum chemical method for calculating excitation energies and transition moments in the vacuum ultraviolet (VUV) which can greatly assist in the scouting of highly transparent materials. We have performed TD-DFT calculations for a broad variety of fluorinated molecules and we will report calculated VUV photoabsorption spectra for a large family of model fluorohexanes. These calculations, which span a range from 1-fluorohexane to CH₃CF₂CF₂CF₂CF₂CH₃, illustrate some of the principles one may use to design low absorption polymeric materials.