Organofluorine compounds are becoming increasingly important in different fields, such as material science, agro chemistry, and the pharmaceutical industry. Nucleophilic trifluoromethylation is one of the widely used methods to incorporate a trifluoromethyl moiety into organic molecules. We have carried out extensive studies to develop varieties of easily accessible nucleophilic catalysts to promote such reactions. TMS-protected trifluoromethylated alcohols were prepared from both aldehydes and ketones in excellent yields using catalytic amount of amine N-oxide. Carbonate and phosphate salts also showed efficient catalytic activity toward this reaction. These reactions were highly solvent dependent, and DMF was found to be the most suitable one among the various solvents studied. All these reactions proceeded under very mild conditions, giving clean products and avoiding the use of any fluoride initiators or expensive catalysts, and extremely water-free conditions. The mechanism for the reaction is discussed in detail. DFT calculations were performed on the possible reaction intermediates using the Gaussian 03 program at B3LYP/6-311+G* level to support the proposed mechanism.

Abstractα,β-Difluoromethylene deoxynucleoside 5'-triphosphates (dNTPs, N = A or C) are advantageously obtained via phosphorylation of corresponding dNDP analogues using catalytic ATP, PEP, nucleoside diphosphate kinase (NDPK) and pyruvate kinase (PK). DNA pol β K d values for the α,β-CF 2 and unmodified dNTPs, α,β-NH dUTP, and the a,β-CH 2 analogues of dATP and dGTP are discussed in relation to the conformations of α,β-CF 2 dTTP v. α,β-NH dUTP bound into the enzyme active site.In an ongoing multidisciplinary study of structure and function of DNA polymerase β, a eukaryotic enzyme primarily involved in filling short DNA gaps 1 , we required a series of α,β-methylene-substituted analogues of deoxynucleoside 5'-triphosphates (dNTPs). When the *Email Address: mckenna@usc.edu. Supporting Information Available General methods used; detailed synthetic procedures and characterization data for 1 -9; analytical and preparative HPLC methods; HPLC studies of conversions of 1 to 2, 2 to 3, 7 to 4, 4 to 5, 5 to 6; 1 H NMR spectra of 1-7 and 9; 31 P and 19 F NMR spectra of 2, 3, 5, 6, 9; 13 C NMR spectrum of 9; analytical HPLC traces for 3, 6 and 9; HRMS spectra for 3 and 6, and LRMS spectrum for 9; DNA synthesis gel analysis of 9 before and after HPLC purification; protocol and inhibition plot for inhibition of pol β dCTP incorporation by 6; crystallographic methods and statistics for the ternary pol β complex with 9; and supplementary literature references are available online at http://pubs.acs.org. P α -O-P β bridging oxygen in a natural mononucleotide substrate is replaced by an imido (NH) 2-4 or methylene (CXY) 4,5 group, the P-N or P-C bond should resist cleavage in the nucleotidyl transfer reaction catalyzed by the enzyme. As a result, these analogues will remain intact in stable ternary DNA complexes with the polymerase and therefore should be useful to probe pre-chemistry enzyme-complex function and structure, as recently shown with in an X-ray crystallographic study of α,β-NH dUTP with DNA pol β. 6 Information about such complexes provides a reference point for theoretical analysis of the chemical mechanism 7 for the complete transfer of a monophosphate nucleoside donor to the sugar acceptor in the active site. As probes for the mechanism of polymerase catalysis and its relationship to polymerase fidelity, α,β-methylene dNTP analogues permit exploration of stereoelectronic effects on active site interactions, by making appropriate substitutions X,Y on the adjacent P α CXY bridging carbon. The largest obtainable electron-withdrawing effect with minimal steric perturbation can be achieved using X,Y = F, resulting in analogues in which the bisphosphonate group is expected to be less basic than the pyrophosphate moiety in the natural dNTPs. 8,9 In this article, we describe the first synthesis of α,β-CF 2 dCTP 6, using a modified chemicalenzymological approach that also can be applied to synthesis of α,β-CF 2 dATP 3, affording these compounds in sufficient purity to virtually eliminate detectable contaminating substrate ...

The potential of using organogermatranes in palladium-catalyzed cross-coupling with aryl iodides has been investigated. We have found that organogermatranes are less reactive in this analogue of Stille coupling than trialkylorganostannanes; nevertheless activation by fluoride promotes the reaction. The hypervalent germanium species produced from the germatranes provide a more efficient and more easily handled reagent than trialkoxygermanium analogues.