42 research outputs found
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Mechanistic studies on Re(V) mediated C-O bond transformations
In situ, reduction of Cp*ReO₃ by PPh₃ to form (Cp*ReO)₂(μ-O)₂ allows catalytic deoxygenation of epoxides, however, conproportionation between Reⱽ and Reⱽᴵᴵ species to form clusters of ((Cp*Re)₃(μ-O)₆}²⁺(ReO₄⁻)2 and new compound {(Cp*Re)₃(μ²-O)₃(μ³-O⁾³ReO₃}⁺(ReO₄⁻) leads to removal of rhenium from the catalytic cycle and loss of activity, The epoxide deoxygenation mediated by (Cp*ReO)₂(μ-O)₂ at least partially occurs through the intermediacy of the corresponding Re(V) diolates, which are unstable under conditions at which they form (72-112°C); the following cycloreversion leads to a formation of Cp*ReO₃ and alkene, Primary ¹³c and secondary ²H kinetic isotope effects (KIE) show that cycloreversion of 4-methoxystyrene from Tp'Re(0)(OCH(Ph-4-OMe)CH₂O) proceeds via a significantly asynchronous but concerted transition state. The primary KIEs are k₁₂c/ᵏ₁₃c = 1 .041 ± 0.005 at the alpha position, and 1.013 ± 0.006 at the beta position. The secondary KIEs were kH/kD = 1.076 ± 0.005 at the alpha position, and 1 .017 ± 0.005 at the beta position at 103°C. Both ¹³C and D KIEs were obtained from analysis of ¹H NMR spectra using a newly developed procedure. For the first time, D KIEs were alternatively obtained using Bayesian NMR methodology, independently confirming D KIEs derived from ¹H NMR. ¹³C and D KIEs were found to be consistent with each other in pointing to significantly more bond breaking at the alpha carbon than at the beta carbon. A Hammett study on cycloreversions of substituted styrenes from a series of Tp'Re(O)(diolato) showed dichotomous behavior for electron donors and electron acceptors as substituents: ρ = -0.65 for electron donors, but ρ = +1.13 for electron-withdrawing groups. Quantitative analysis of the KIEs coupled with the observed impact of aryl substitution on the rate of cycloreversion excludes the possibility of competing single bond-cleaving (stepwise) processes being responsible for the observed KIE values. DFT calculations locate a transition state structure for styrene extrusion that agrees with this picture. The Hammett behavior opens the possibility that, depending on a substituent, two different mechanisms might be in competition due to very well balanced stereoelectronics of the system where charge perturbation changes the mechanism
Automated Solid-Phase Radiofluorination Using Polymer-Supported Phosphazenes
The polymer supported phosphazene bases PS-P2tBu and the novel PS-P2PEG allowed for efficient extraction of [18F]F− from proton irradiated [18O]H2O and subsequent radiofluorination of a broad range of substrates directly on the resin. The highest radiochemical yields were obtained with aliphatic sulfonates (69%) and bromides (42%); the total radiosynthesis time was 35–45 min. The multivariate analysis showed that the radiochemical yields and purities were controlled by the resin load, reaction temperature, and column packing effects. The resins could be reused several times with the same or different substrates. The fully automated on-column radiofluorination methodology was applied to the radiosynthesis of the important PET radiotracers [18F]FLT and [18F]FDG. The latter was produced with 40% yield on a 120 GBq scale and passed GMP-regulated quality control required for commercial production of [18F]FDG. The combination of compact form factor, simplicity of [18F]F− recovery and processing, and column reusability can make solid phase radiofluorination an attractive radiochemistry platform for the emerging dose-on-demand instruments for bedside production of PET radiotracers
Towards automated solid phase radiofluorination for dose-on-demand PET: retention of activity by solid support
On-column [18F]fluoride trapping and radiofluorination of 2-(naphthalen-1-yl)ethyl-4-methylbenzenesulfonate (C10H7(CH2)2OTs), performed on polystyrene supported phosphazene base PS-PtBu2 yielded [18F]1-(2-fluoroethyl)naphthalene ([18F]C10H7(CH2)2F) in 50% radiochemical yield but left up to 43% of activity unreacted on the resin. This activity could be eluted with Kryptofix/K2CO3 and then used for conventional radiofluorination of the same substrate, suggesting that the column-retained activity was present in the form of [18F]fluoride entrapped in polymer matrix. An approach to minimize the amount of entrapped [18F]fluoride by use of glass beads functionalized with alkylsilane-derivatized phosphazene residues was attempted but was stymied by fluorolysis/hydrolysis of the alkylsilane spacer. The results suggest that the key to high yield of on-column radiofluorination is to minimize the residual [18F]fluoride absorption in the matrix by the judicious choice of solid support