Silyl Fluoride Research Articles

Fluorination of silyl prosthetic groups by fluorine mediated silyl ether linker cleavage: a concept study with conditions applicable in radiofluorination

BackgroundPositron emission tomography (PET) is a powerful tool in medical imaging, especially in combination with the PET radionuclide fluorine-18 that possesses optimal characteristics. For labelling of biomolecules and low-molecular weight tracers, fluorine-18 can be covalently bound to silicon by either nucleophilic replacements of leaving groups (like ethers) or by isotope exchange of fluorine-19. While nucleophilic substitutions require additional purification steps for the removal of contaminants, isotope exchange with fluorine-18 results in low molar activity. Both challenges can be addressed with a detagging-fluorination of an immobilized silyl ether motif.ResultsBy overcoming the susceptibility towards hydrolysis, optimized detagging conditions (improved reaction time, fluorination reagent, linker, and resin) could afford the highly sterically hindered silyl fluoride motifs, that are commonly applied in radiochemistry in small and semipreparative scales. The described reaction conditions with fluorine-19 are transferrable to conditions with [18F]fluoride and silyl fluorides were obtained after approx. 10 min reaction time and in high-purity after mechanical filtration.ConclusionsWe present a proof-of-concept study for a detagging-fluorination of two silyl ethers that are bound to an optimized amino alcohol resin. We show with our model substrate that our solid-phase linker combination is capable of yielding the desired silicon fluoride in amounts sufficient for biological studies in animals or humans under standard fluorination conditions that may also be transferred to a radiolabelling setting. In conclusion, our presented approach could optimize the molar activity and simplify the preparation of radiofluorinated silyl fluorides.

Structural, energetic, and vibrational properties of the homodimers of the silyl, germyl, and stannyl halides, (MH3X)2 (M = Si, Ge, Sn; X = F, Cl, Br, I)

A number of properties of the homodimers of the three families of molecules MH3X, where M is Si, Ge, and Sn and X is F, Cl, Br, and I are computed. The results are compared with those of a similar study of the homodimers of the methyl halides containing the same four halogen atoms, and some notable differences are observed among related sets of monomer species. The interaction energies, the primary intermolecular geometrical parameters, the changes in the intramolecular bond lengths, and the vibrational data (wavenumber shifts and dimer/monomer infrared intensity ratios) of some of the modes most closely associated with the site of interaction show, for the most part, regular variations as the central atom and the halogen atom are systematically varied. The results are interpreted in terms of the changes in the bonding properties of the monomer molecules as they undergo dimerization. Graphical abstract Interaction energies of the silyl, germyl and stannyl fluoride, chloride, bromide and iodide dimers.

Experimental values of the rotational and vibrational constants of deuterated silyl fluoride

ABSTRACTAccurate experimental values of the αA and αB rotation–vibration interaction, and ωi, xij and gij vibrational constants have been extracted from the most recent high-resolution Fourier transform infrared and millimetre-wave measurements in the spectra of the prolate symmetric top SiD3F, between 400 and 2000 cm−1. From the experimental values of the ground state rotational and rovibrational interaction parameters, accurate equilibrium rotational constants have been derived: Ae = 1.432326 (12) cm−1 and Be = 0.4112012 (45) cm−1 for silyl fluoride. The effective ground state structure has also been determined from the observed moments of inertia of SiD3F: r0(Si-D) = 1.4755 (29) Å; r0(Si-F) = 1.5931 (26) Å; θ0(DSiD) = 110.47 (32)° and θ0(DSiF) = 108.45 (56)°. A merge of equilibrium moments of 28SiH3F and 28SiD3F yielded an experimental equilibrium structure of silyl fluoride. This geometry has been found in good agreement with semi-experimental median values, as well as with the recent semi-experimental ab initio equilibrium structure obtained using all data available of the various isotopic species of silyl fluoride.

ChemInform Abstract: Silyl Fluoride Electrophiles for the Enantioselective Synthesis of Silylated Pyrrolidine Catalysts.

Abstract(‐)‐Sparteine‐mediated treatment of the pyrrole (I) with the silyl fluorides (II) allows efficient and highly stereoselective access to the products (III).

18F-Labeled Modified Porous Silicon Particles for Investigation of Drug Delivery Carrier Distribution in Vivo with Positron Emission Tomography

Because of its biocompatibility and ability to accommodate a variety of payloads from poorly soluble drugs to biomolecules, porous silicon (PSi) is a lucrative material for the development of carriers for particle-mediated drug delivery. We report a successful direct one-step (18)F-radiolabeling of three types of PSi microparticles, thermally hydrocarbonized THCPSi, thermally oxidized TOPSi, and thermally carbonized TCPSi for the investigation of their biodistribution in vivo with positron emission tomography as part of their evaluation as carriers for particle-mediated drug delivery. FTIR and XPS characterization of the PSi materials after carrier-added (18)F/(19)F-radiolabeling reveals that depending on the material the (18)F-labeling is likely to be accomplished either by substitution for surface silyl hydrogen or silyl fluoride or by nucleophilic attack of (18)F(-) to Si-O-Si bridges. With the selected (18)F-radiolabeling method, good to excellent in vitro radiolabel stability in simulated gastric and intestinal fluids and in plasma is achieved for all the particle types studied. Finally, a preliminary evaluation of (18)F-THCPSi microparticle biodistribution in the rat gastrointestinal tract after oral administration is reported, illustrating the utility of using (18)F-radiolabeled PSi as imaging probes for PSi-based drug delivery carrier distribution in vivo.

Silyl Fluoride Electrophiles for the Enantioselective Synthesis of Silylated Pyrrolidine Catalysts

Chiral silylated pyrrolidine catalysts are obtained in high yield and enantioselectivity by sparteine-mediated lithiation of N-Boc-pyrrolidine and addition to silyl fluoride electrophiles. The activity and enantioselectivity of a new tert-butyldiphenylsilylpyrrolidine catalyst has been demonstrated for various asymmetric Michael reactions at 5 mol % catalyst loading and affords up to 99% ee for asymmetric Michael reactions with aldehydes and nitro-olefins. Acetaldehyde donors proceed with yields up to 77% and enantioselectivities up to 96% ee, avoiding common side reactions that often lower yields. Insight into the mechanism of pyrrolidine-based catalysts is provided by demonstrating ESI mass spectrometry evidence for activation of a nitro acceptor by formation of a hydrogen-bonding adduct with the catalyst amine. Analysis of reaction intermediates using mass spectrometry provides evidence that the pyrrolidine catalyst also plays a role in activating nitro-olefins through hydrogen-bonding.

The infrared band intensities and other properties of the homodimers of the methyl and silyl halides: An ab initio study

Abstract The properties of the homodimers of methyl and silyl fluoride, chloride and bromide have been determined by means of ab initio molecular orbital calculations. The interaction energies, molecular structures, vibrational spectra and molecular orbital properties have been investigated, and some common features within each family have been observed. A number of systematic differences in the properties of the dimers have also been noted and rationalized. Typically, discussion of the results of such calculations has focused on the vibrational wavenumber shifts occurring on complexation, and the accompanying changes in the infrared band intensities have received relatively little attention. This paper aims to reposition infrared intensities as valid and useful parameters with which to interpret the formation of the homodimers of polar molecules.

Rotational spectra of isotopic species of silyl fluoride. Part II: Theoretical and semi-experimental equilibrium structure

The equilibrium structure of silyl fluoride, SiH 3F, has been reinvestigated using both theoretical and experimental data. With respect to the former, quantum-chemical calculations at the coupled-cluster level have been employed together with extrapolation to the basis set limit, consideration of higher excitations in the cluster operator, and inclusion of core correlation as well as relativistic corrections ( r(Si–F) = 1.5911 Å, r(Si–H) = 1.4695 Å, and ∠FSiH = 108.30°). A semi-experimental equilibrium structure has been determined based on the available rotational constants for the various isotopic species of silyl fluoride ( 28SiH 3F, 28SiD 3F, 29SiH 3F, 29SiD 3F, 30SiH 3F, 30SiD 3F, 28SiH 2DF, and 28SiHD 2F) together with computed vibrational corrections to the rotational constants ( r(Si–F) = 1.59048(6) Å, r(Si–H) = 1.46948(9) Å, and ∠FSiH = 108.304(9)°).

Rotational spectra of isotopic species of silyl fluoride. Part I: Lamb-dip measurements and quantum-chemical calculations

The Lamb-dip technique has been employed for recording the rotational spectra of three isotopic species of silyl fluoride, namely 28SiH 3F, 29SiH 3F, and 30SiH 3F, in order to improve the knowledge of their spectroscopic parameters as well as to try to resolve their hyperfine structure. High-level quantum-chemical computations using state-of-the-art coupled-cluster techniques together with core-polarized correlation-consistent basis sets have been employed to provide reliable reference values for the hyperfine parameters involved and have been used to guide the experimental investigation. Analysis of the experimental spectra allowed to improve the accuracy of the known spectroscopic parameters as well as to determine for the first time sextic and octic centrifugal-distortion constants.

Conformational Stability from Rare Gas Solutions, r0 Structural Parameters, Barriers to Internal Rotation, and Ab initio Calculations for Vinyl Silyl Fluoride

The Raman (3300-10 cm(-1)) and infrared (3300-40 cm(-1)) spectra of gaseous and solid vinyl silyl fluoride, CH(2)=CHSiH(2)F, have been recorded. Raman spectrum of the liquid has also been recorded and depolarization values obtained. Variable-temperature studies of the infrared spectra of the sample dissolved in liquid krypton (-110 to -150 degrees C) and liquid xenon (-60 to -100 degrees C) have been carried out. From these studies, the enthalpy difference has been determined to be 76 +/- 7 cm(-1) (0.91 +/- 0.08 kJ/mol) from the krypton solutions and 69 +/- 7 cm(-1) (0.82 +/- 0.08 kJ/mol) from the xenon solutions, with the gauche conformer the more stable form. From the far-infrared spectrum of the gas, the asymmetric torsional fundamentals for the cis and gauche conformers have been observed at 102.34 and 86.56 cm(-1), respectively, with each having several "hot bands" falling to lower frequencies. From these frequencies along with the experimentally determined conformational enthalpy difference, as well as the gauche skeletal dihedral angle, the potential function governing the conformational interchange has been determined with the following Fourier cosine potential coefficients: V(1) = -80 +/- 11, V(2) = -42 +/- 15, V(3) = 622 +/- 5, V(4) = 34 +/- 5, and V(6) = -31 +/- 2 cm(-1). The gauche-to-cis and gauche-to-gauche barriers are 664 cm(-1) (7.94 kJ/mol) and 608 cm(-1) (7.27 kJ/mol), respectively. Complete vibrational assignments are provided for both conformers. In addition, equilibrium geometries and electronic energies have been determined for both rotamers from ab initio calculations using restricted Hartree-Fock and Møller-Plesset perturbation method to the second order (MP2), as well as density functional theory by the B3LYP methods, employing a number of basis sets up to 6-311+G(2df,2pd). All levels of calculation predict the gauche conformer to be the more stable form. By systematically adjusting the ab initio predicted structural values to fit the previously reported microwave rotational constants, adjusted r(0) parameters have been obtained for both conformers. These values are compared to those for the corresponding chloride and methyl compounds. The spectroscopic and theoretical results are discussed and compared to the corresponding quantities for some similar molecules.

Facile Intermolecular Aryl−F Bond Cleavage in the Presence of Aryl C−H Bonds: Is the η2-Arene Intermediate Bypassed?

The complex TpW(NO)(PMe3)(η2-benzene) cleanly inserts into the C−F bond of fluorobenzene to form the seven-coordinate complex TpW(NO)(PMe3)(F)(Ph) (confirmed by X-ray diffraction), while no C−H insertion is detected. Treatment of this product with triethyl- or phenyldimethylsilane results in liberation of benzene and the corresponding silyl fluoride. DFT calculations suggest a low-energy reaction pathway for C−F activation involving a fluorine-bound σ-complex that does not require the presence of an η2-arene intermediate. As the fluorine content of the benzene increases, or the benzene is replaced by fluoronaphthalene, C−F addition is no longer observed, and either C−H addition or η2-coordination dominates. Two species thought to be η2-silanes are also reported.

Mechanistic studies on the catalytic cycle of metal fluoride-catalyzed allylation using allyltrimethoxysilane in protic solvents.

The catalytic cycles of CdF(2).1-catalyzed and AgF.BINAP-catalyzed allylation using allyltrimethoxysilane in protic solvents were investigated. The experimental and (19)F NMR studies strongly supported that metal fluorides were regenerated from silyl fluoride species, and that these reactions were truly fluoride-catalyzed reactions. It was revealed that these catalytic cycles were much different from that of TBAF-catalyzed allylation using allyltrimethylsilane in THF.

The Equilibrium Structure of Silyl Fluoride

The experimental equilibrium structure of silyl fluoride has been determined using new sets of accurate rotational constants that have recently been obtained by taking into account the most important interactions between the excited vibrational states. The equilibrium structure has also been calculated at the CCSD(T) level of theory with the cc-pVQZ+1 basis set (including corrections for the core correlation). The anharmonic force field up to semidiagonal quartic terms has been calculated at the MP2 level of theory and the equilibrium structure has been derived from the experimental rotational constants and the ab initio rovibrational interaction parameters. Finally, the average structure of both 28SiH 3F and 28SiD 3F has been reevaluated and used to derive the equilibrium structure. These structures are compared and the experimental structure is found to be in slight disagreement with the other ones. The preferred structure is obtained by calculating the median value of the different structures. The results are r e(SiF)=1.5907 (9) Å, r e(SiH)=1.4696 (13) Å, ∠ e(HSiF)=108.32(15)°, and ∠ e(HSiH)=110.60(14)°.

Transition states for inversion and retention of configuration channels in the reactions of alkyl and silyl fluorides with a water molecule

The potential energy surface of CH 3F+H 2O and SiH 3F+H 2O systems were scanned by B3LYP and MP2 methods. For each system two channels of reactions, i.e. with retention and inversion of configuration, were explored by modelling the front-side and the back-side attack of the water molecule. In each case the barrier heights for two channels were predicted. The inversion channels have similar and high energy barriers for both systems while the substantial difference was found for the retention channel barriers between methyl and silyl fluorides. The lower barrier for silyl fluoride is in keeping with experimental observations.

The anharmonic force fields of silyl fluoride and silyl chloride

The complete cubic and quartic force fields of H 3SiF and H 3SiCl are predicted from ab initio SCF calculations using the 6–31G ∗ basis set. The computed geometries, rotational constants, vibrational wavenumbers, anharmonicity constants, vibration-rotation interaction constants, l-doubling constants, Coriolis coupling constants, and centrifugal distortion constants are compared with the available experimental data. Many experimentally unknown spectroscopic constants are predicted, especially for D 3SiF and D 3SiCl.

Structure of silyl fluoride, SiH3F, at 96 K

Structure of silyl fluoride, SiH3F, at 96 K

Assignment of far infrared laser lines in silyl fluoride

Eleven far i.r. laser lines, generated by optical pumping with a CO 2 laser, have been assigned with the aid of available spectroscopic data and an accurate calculation of the vibration—rotation spectrum around 10 μm. The absorbing i.r. transitions coincident with the laser are in the ν 2 and ν 5 bands of 28SiH 3F which are strongly perturbed by Coriolis and l-type doubling effects. Predicted far i.r. transition wavenumbers are in close agreement with experiment and with predictions derived from a recent extensive FTIR and laser study in the 10 μm region.

The crystal structure of silyl fluoride at 96 K

The crystal structure of silyl fluoride at 96 K

Laser Stark spectroscopy of silyl fluoride in the 10-μm region: Analysis of the ν2 and ν5 bands

The v 2 = 1 and v 5 = 1 states of silyl fluoride are strongly mixed by Coriolis coupling. About 1100 Stark tuned resonances were measured in these bands using 12CO 2 and 13CO 2 lasers. These data were combined with 13 new millimeterwave measurements and 900 Fourier transform infrared measurements in a suitable model. Apart from the main Coriolis coupling ζ 25, it was necessary to include estimates of two further Coriolis terms to obtain a satisfactory interpretation of the data. Many vibration-rotation parameters and the dipole moments are determined.

New cw FIR laser lines from optically pumped silyl fluoride (SiH3F)

FIR laser action has been observed for the first time in a molecule containing silicon: silyl fluoride, SiH3F. Eleven new cw optically pumped lines between 187 and 1014μm were detected from both open resonator and waveguide structures. Although the chlorine analogue, SiH3Cl, showed strong absorption at every CO2 laser frequency no FIR laser emission was detected at the pump powers available.