Neighboring group participation in the additions of iodonium and bromonium ions to N-alkoxycarbonyl-2-azabicyclo[2.2.n]alk-5-enes (n = 1,2).

Additions of iodonium-X reagents to N-alkoxycarbonyl-2-azabicyclo[2.2.1]hept-5-enes and the homologous 2-azabicyclo[2.2.2]oct-5-enes have been found to mirror the outcomes of additions of bromonium-X reagents. Only rearranged products were observed for reactions of either of these halonium ion reagents with the azabicylo[2.2.1]hept-5-enes. For the azabicyclo[2.2.2]oct-5-enes, nitrogen participation in addition of IOH or BrOH was dependent on the N-alkoxycarbonyl group. With larger N-Boc, N-Cbz, or N-Troc protecting groups, unrearranged 5-anti-hydroxy-6-syn-I(or Br)-2-azabicyclo[2.2.2]octanes were formed by nucleophilic attack at C(5) on syn-halonium ions. The structure of N-methyl-8-anti-bromo-4-anti-hydroxy-2-azabicyclo[3.2.1]octane has been reassigned by X-ray analysis.

Selectfluor as a nucleofuge in the reactions of azabicyclo[n.2.1]alkane beta-halocarbamic acid esters (n = 2,3).

The ability of Selectfluor to act as a nucleofuge for hydrolysis of beta-anti-halides was investigated with N-alkoxycarbonyl derivatives of 6-anti-Y-7-anti-X-2-azabicyclo[2.2.1]heptanes and 4-anti-Y-8-anti-X-6-azabicyclo[3.2.1]octanes. The azabicycles contained X = I or Br groups in the methano bridge and Y = F, Br, Cl, or OH substituents in the larger bridge. The relative reactivities of the halides were a function of the azabicycle, the halide, and its bridge and the addition of Selectfluor or HgF(2) as a nucleofuge. All halide displacements occurred with retention of stereochemistry. Selectfluor with sodium bromide or sodium chloride, but not sodium iodide, competitively oxidized some haloalcohols to haloketones. A significant 15.6 Hz F...HO NMR coupling was observed with 4-anti-fluoro-8-anti-hydroxy-6-azabicyclo[3.2.1]octane.

A novel coaxial electrospray ionization method for characterizing hexacosanoylceramides by Fourier transform ion cyclotron resonance mass spectrometry.

Because of poor aqueous solubility and lack of UV chromophores, the characterization of long-chain hydrocarbons and ceramides by conventional UV and mass spectrometric methods has not been successful. Therefore, a novel coaxial electrospray ionization method was developed for characterizing reaction products of phytosphingosine and hexacosanoic acid in toluene and tetrahydrofuran (THF), by high resolving power Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). Simultaneous spraying of a solution of apolar analytes and polar reagents into the gas phase readily enabled protonation and/or sodiation of analyte with enhanced signal-to-noise (S/N). Sample introduction was by direct infusion such that the sprayers were arranged either along the instrument line-of-sight (for monospray and coaxial spray modes) or in a 45 degrees configuration for dual-spray mode. For dual-spray and coaxial spraying, p-toluenesulphonic acid was used as a reagent and sprayed simultaneously with the analyte dissolved in toluene or THF. Compounds were characterized by accurate mass measurement of the protonated and/or sodiated molecules.

Acetonitrile/water gas-phase reaction products observed by use of atmospheric pressure chemical ionization: adducts formed with sulfonamides.

Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are the two most common mass spectrometric ionization methods used in the pharmaceutical industry. However, APCI analysis can sometimes lead to ambiguity in compound characterization and quantitation due to gas-phase reactions occurring between acetonitrile and water in the plasma, and between these plasma-generated compounds and the analyte. During the analysis of various sultams and sulfonamides we observed signals corresponding to m/z [M+44](+) and [M+60](+). Various solvent conditions and collisionally activated dissociation MS(n) experiments revealed that under the high-energy plasma conditions of APCI, the acetonitrile/water solvent mixture reacts undergoing acid-catalyzed hydrolysis producing acetamide, 59 Da. Further, the highly reactive 43 Da species ethanimine is also produced. These two compounds, normally not observed in APCI analysis, are stabilized by the sulfonamide and appear as adduct species in the mass spectra. The sulfone oxygens and the lone pair of electrons on the amide nitrogen play a role in stabilizing this adduct.

Novel selectfluor and deoxo-fluor-mediated rearrangements. New 5(6)-methyl and phenyl methanopyrrolidine alcohols and fluorides.

Stereoselective syntheses of novel 5,6-difunctionalized-2-azabicyclo[2.1.1]hexanes containing 5-anti-fluoro or hydroxyl in one methano bridge and a variety of syn- or anti-chloro, fluoro, hydroxy, methyl, or phenyl substituents in the other methano bridge have been effected. Rearrangements of iodides to alcohols were initiated using Selectfluor. Rearrangement of alcohols to fluorides was initiated using Deoxo-Fluor. Ring opening of 2-azabicyclo[2.2.0]hex-5-ene exo-epoxide with organocopper reagents is regioselective at C(5).