Synthesis of alpha-fluorosulfonamides by electrophilic fluorination

Alpha-fluorosulfonamides were prepared by electrophilic fluorination of tertiary sulfonamides using N-fluorobenzenesulfonimide as fluorinating agent and utilizing the dimethoxybenzyl group (DMB) as a new sulfonamide protecting group. Removal of the DMB group with TFA/CH(2)Cl(2) gave primary and secondary alpha-fluorosulfonamides.     

Mechanochemical electrophilic fluorination of liquid beta-ketoesters

An improved substrate scope for the mechanochemical electrophilic fluorination of dicarbonyls is reported. The applicable substrates have now been broadened to include liquid β-ketoesters. Key to this capability is the inclusion of a grinding auxiliary (NaCl) to improve mass transfer and prevent pasting or gumming of the reaction mixture. Notably, the use of a small amount of acetonitrile is critical to increasing the rate of reaction, ensuring complete consumption of starting materials during the short reaction times as well as improving the selectivity for the monofluorinated product in the mill.     

Selective anodic fluorination of electrophilic alkenes

Anodic fluorination of some electrophilic alkenes (conjugated with electron-withdrawn groups), ethyl cinnamates, RC₆H₄CHCHCO₂Et (R = H, CH₃, CH₃O, F and CF₃), cinnamonitrile, C₆H₄CHCHCN, phenyl stryryl ketone, and t-butyl styryl ketone using ammonium fluorides as the fluorine source and supporting electrolyte, in CH₂Cl₂ as electrolytic solvent yields the expected vicinal difluoro compounds, as mixture of erythro and threo isomers. The anodic fluorination of phenyl 3,5-di-t-butyl-4-hydroxystyryl ketone yields two monofluoro compounds. A possible reaction mechanism is discussed.     

Synthesis of difluorinated pyridinecarboxaldehyde via electrophilic fluorination

An efficient synthesis of novel 3,5-difluoropyridine-4-carboxaldehyde using N-fluoro-benzenesulfonimide (NSFi) is described. Difluorination was achieved through the reaction of 3,5-dihalo-1,3-dioxolane pyridine with n-butyllithium followed by N-fluorobenzenesulfonimide at −120 °C in good to high yields. Maintaining the low temperature during the transmetallation was found to be critical for the selective formation of the difluoro-susbstitution over the monofluoro one.     

Mechanism of electrophilic fluorination of aromatic compounds with NF-reagents

Kinetic isotope effects H/D in electrophilic fluorination of aromatic compounds with NF-reagents were investigated. The small values of k _H/k _D (0.86–1.00) are in agreement with the polar reaction mechanism where the Wheland complex decomposition is not the limiting stage. The fluorination of 1,3,5-trideuterobenzene was established by ¹H and ¹⁹F NMR spectroscopy to occur with a 1,2-migration of a hydrogen (deuterium) atom. The analysis of Brown-Stock relationship demonstrated that the activity of NF-reagents exceeded that of many known electrophilic systems including halogenation, but it was essentially less than the activity of elemental fluorine.     

Investigation of radical cation in electrophilic fluorination by ESI-MS

Reaction solutions of selectfluor (1) with triphenylethylene (4a) and tetraphenylethylene (4b) were monitored by ESI-MS and ESI-MS/MS. Detection and characterization of the key radical cationic intermediates 5a.+ and 5b.+) fully supports the SET mechanism in electrophilic fluorination as depicted above. [reaction: see text]     

Metal-free electrophilic fluorination of alkyl trifluoroborates and boronic acids

Secondary alkyl trifluoroborates undergo facile electrophilic fluorination under mild conditions to afford the corresponding benzylic fluorinated adducts in excellent yield.     

Microwave-assisted rapid electrophilic fluorination of 1,3-dicarbonyl derivatives with Selectfluor

A microwave-assisted fluorination method for 1,3-dicarbonyl compounds using Selectfluor^® has been developed. 2-Monofluorinated products can be obtained in high yield in neutral reaction conditions with addition of 1 eq. of Selectfluor^®. Treatment of 1,3-dicarbonyls with 3 eq. of Selectfluor^® in the presence of tetrabutylammonium hydroxide (TBAH) as the base results in the formation of 2,2-difluorinated derivatives only.     

Computational and experimental evidence for the structural preference of phenolic C-8 purine adducts

The structural and spectral properties of (ortho and para) C8-aryl-purine adducts formed from carbon attachment by phenolic toxins were investigated through DFT calculations and UV-vis absorbance and emission studies. The global minima of both the deoxyadenosine (dA) and deoxyguanosine (dG) adducts adopted a syn conformation about the glycosidic bond due to the presence of an O5'-H...N3 hydrogen bond, where the anti minima are 20-30 kJ mol-1 higher in energy. While the nucleobase adducts are planar, the presence of the deoxyribose sugar induces a twist about the carbon-carbon bond connecting the phenol and nucleobase rings. ortho-Phenolic adducts are less twisted than the corresponding para adducts due to stabilization provided by an intramolecular O-H...N7 bond. Solvation calculations, in combination with UV-vis studies, demonstrate that the structural preference is solvent dependent, where solvents with hydrogen-bonding abilities disrupt the intramolecular O-H...N7 hydrogen bond such that a greater degree of twist is observed, and less polar solvents stabilize the planar structure. Indeed, the ratio of twisted to planar conformers is estimated to be as large as 50:50 in some aprotic solvents. Thus, the combined experimental and computational approach has provided a greater understanding of the structure of the ortho- and para-dA and dG C-bonded phenoxyl adducts as the first step to understanding the biological consequences of this form of DNA damage.     

Enantioselective and diastereoselective synthesis of fluorinated dipeptides by late electrophilic fluorination

A series of optically enriched monofluorinated dipeptides incorporating an α-fluoro-α-amino acid were prepared by enantio- and diastereoselective electrophilic fluorination. This previously unsuccessful approach to fluorinated dipeptides can now be achieved with up to 73:27 enantiomeric ratio and high >98:2 diastereomeric ratio.     

Synthesis of aryl allylic fluorides by direct electrophilic fluorination of alkenes

Aryl allylic fluorides were synthesized in 47-83% yields by using Selectfluor as the electrophilic reagent in DMF. The outcome of this reaction may be explained by electronic effects while the reactivity was controlled by the stabilization effect of the aryl group on the benzylic cationic intermediates.     

Screening of chiral catalysts for enantioselective electrophilic fluorination of β-ketoesters

A variety of oxygen- and nitrogen-containing chiral ligands in combination with various metals have been screened in the enantioselective electrophilic fluorination of β-ketoesters. This study involved the use of readily available substrates, chiral ligands and electrophilic fluorinating agents. In particular, heterobimetallic Al-Li-BINOL complex allowed to obtain enantiomerically enriched α-fluoro-β-ketoesters in high yields and moderate enantioselectivities; up to 67% ee. A comparison with previously reported chiral ligands is provided.     

A cooperative allylic fluorination: combination of nucleophilic and electrophilic fluorine sources

A one step, regioselective allylic fluorination of alkenes is reported in which electrophilic and nucleophilic sources of fluorine act synergistically to afford rearranged allylic fluorides over alternative vicinal dihalides. The reaction occurs under exceptionally mild conditions and without need for prefunctionalization or transition metal catalysts. The fluorination of cyclic alkenes and monoterpenes is highlighted, and preliminary mechanistic experiments reveal that dual (radical and ionic) pathways operate simultaneously.     

Chemistry of pyrones related to dehydroacetic acid. Functionalization at C-5 and at the methyl group at C-6. An attempted synthesis of a thromboxane B2 analogue

New derivatives of dehydroacetic acid and triacetic acid lactone functionalized at both C-5 and at the methyl group at C-6 have been synthesized as intermediates for the preparation of thromboxane B₂ analogues. 6-Mercaptomethyl-4-methoxy-2-pyrone and some derived thioethers have been also prepared. New thioether derivatives of O-alkyloximes of dehydroacetic acid have been synthesized and tested for herbicidal activity.     

Bromination at C-5 of Pyrimidine and C-8 of Purine Nucleosides with 1,3-Dibromo-5,5-dimethylhydantoin

Treatment of the protected and unprotected nucleosides with 1,3-dibromo-5,5- dimethylhydantoin in aprotic solvents such as CH(2)Cl(2), CH(3)CN, or DMF effected smooth bromination of uridine and cytidine derivatives at C-5 of pyrimidine rings as well as adenosine and guanosine derivatives at C-8 of purine rings. Addition of Lewis acids such as trimethylsilyl trifluoromethanesulfonate enhanced efficiency of bromination.     

An unusual reaction at C-3 of 4-methoxy-6-methyl-2-pyrone

Triacetic acid lactone methyl ether, 4, can be lithiated at C-3 under kinetically controlled conditions. Further reaction with (E)-2-methyl-3-(4-nitrophenyl)propenal results in an unusual condensation at C-3.     

The effect of two electron-withdrawing groups on remote tertiary hydrogens susceptible to electrophilic fluorination using F2

The direct electrophilic fluorination of unactivated remote tertiary hydrogens is effected by the number, nature and distance of electron-withdrawing groups. The effect of these groups on reducing electron density of the tertiary CH bond seems to be additive. The more remote these groups are from the reaction center, the higher the yield of the fluorination.     

An Unusual Formation of Cyclic Sulfite at C-4 and C-5 Positions of Taxane

An unusual formation of cyclic sulfite at C-4 and C-5 positions of taxane was accomplished by treatment of compound 1 with excess MeSOEC1/Et3N and a possible mechanism was proposed.     

Intramolecular electrophilic displacement of acyl by nitro group during attempted synthesis of 3-nitrocoumarins

2-Hydroxyacetophenones undergo upon nitration in acetic acid a substitution of the acyl by nitro group followed by an intramolecular 1,3-acyl shift reminescent of a retro-Fries rearrangement to yield phenyl esters.