The preparation of stable aziridinium ions and their ring-openings

The reaction of enantiomerically pure 2-substituted 1-phenylethyl-aziridine with methyl trifluoromethanesulfonate generated a stable methylaziridinium ion, which was reacted with various external nucleophiles, including nitrile, to yield synthetically valuable and optically pure acyclic amine derivatives in a completely regio- and stereoselective manner.     

Stereoselective synthesis of β-functionalized α-aminophosphonates via aziridinium ions

1,2-Diamino-, 1-amino-2-hydroxy- and 1-amino-2-chloro-2-phenylethylphosphonates were obtained in a stereo- and regioselective manner from 2-amino-1-hydroxy-2-phenylethylphosphonate through the intermediacy of an aziridinium ion.     

Ketalization of gaseous acylium ions

A novel reaction of gaseous acylium ions: ketalization with diols and analogs, has been systematically studied via pentaquadrupole MS2 and MS3 experiments and ab initio calculations. A variety of alpha,beta-diols and their amino, thiol, ether, and thioether analogs have been tested for reactivity, mechanism evaluation, site selectivity, and for the effects of alpha- and beta-interfunctional separation. As for condensed-phase ketalization of neutral carbonyl compounds followed by hydrolysis, gaseous acylium ions are chemically deactivated in the form of cyclic ionic ketals by ketalization, and are efficiently released via on-line collision-induced dissociation. Ketalization of acylium ions is shown to identify and structurally characterize alpha,beta-diols and their analogs, and to distinguish regioisomers. Diastereomers can also be distinguished, as illustrated for cis and trans 1,2-diaminocyclohexane. The MS2 and MS3 data together with 18O-labeling and ab initio calculations establish for acylium ion ketalization a mechanism of anchimeric assistance with participation of the neighboring acyl group.     

Studies on the [2,3]-Stevens rearrangement of aziridinium ions

The aziridinium ylide generated by the intramolecular reaction of a metal carbenoid tethered to a vinylaziridine undergoes [2,3]-Stevens rearrangement to furnish the indolizidine skeleton. It is essential that the correct nitrogen invertomer is used or a competing [1,5]-hydrogen shift predominates. During the preparation of a second system a `one-pot' acylation-[3,3]-Claisen rearrangement was observed, delivering a seven-membered lactam.     

Applications of aziridinium ions. Selective syntheses of beta-aryl-alpha,beta-diamino esters

[formula: see text] alpha,beta-Diamino esters are readily prepared through stereospecific and regioselective opening of an aziridinium ion intermediate with a variety of amines. The aziridinium ion is generated from the epoxide in two steps.     

N-Cyanomethyl-β-chloroamines: a convenient source of aziridinium ions

N-Cyanomethyl-β-chloroamines smoothly react with a range of alcohols or amines to give regio- and stereoselectively 1,2-aminoethers or 1,2-diamines. The reaction proceeds through the formation of an intermediate aziridinium ion. The N-cyanomethyl group can then be cleaved easily.     

Formation and stability of gaseous tolyl ions

Collisional activation mass spectra confirm that tolyl ions can be produced from a variety of CH₃C₆H₄Y compounds. High purity o-, m- and p-tolyl ions are prepared by chemical ionization of the corresponding fluorides (Y=F) as proposed by Harrison. In electron ionization of CH₃C₆H₄Y formation of the more stable tropylium and benzyl ionic isomers usually accompanies that of the o-, m- and p-tolyl ions. Isomerization of low energy [CH₃C₆H₄Y]⁺? to [Y–methylenecyclohexadiene]⁺? is proposed to account for most [benzyl]⁺ formation, while the tropylium ion appears to arise from the isomerization of tolyl ions formed with higher internal energies, [o-, m-, p-tolyl]⁺→ [benzyl]⁺→ [tropylium]⁺, consistent with Dewar's predictions from MINDO/3 calculations.     

Transacetalization with gaseous carboxonium and carbosulfonium ions

Primary carboxonium (H2C=O+-R) and carbosulfonium (H2C=S+-R) ions (R = CH3, C2H5, Ph) and the prototype five-membered cyclic carboxonium ion are found to react in the gas phase with cyclic acetals and ketals by transacetalization to form the respective O-alkyl-1,3-dioxolanium and S-alkyl-1,3-oxathiolanium ions. The reaction, which competes mainly with proton transfer and hydride abstraction, initiates by O-alkylation and proceeds by ring opening and recyclization via intramolecular displacement of the carbonyl compound previously protected in its ketal form. As indicated by product ion mass spectra, and confirmed by competitive reactions, carbosulfonium ions are, by transacetalization, much more reactive than carboxonium ions. For acyclic secondary and tertiary carboxonium ions bearing acidic alpha-hydrogens, little or no transacetalization occurs and proton transfer dominates. This structurally related reactivity distinguishes primary from both secondary and tertiary ions, as exemplified for the two structural isomers H2C=O+-C2H5 and CH3C(H)=O+-CH3. The prototype five- and six-membered cyclic carboxonium ions react mainly by proton transfer and adduct formation, but the five-membered ring ion also reacts by transacetalization to a medium extent. Upon CID, the transacetalization products of the primary ions often dissociate by loss of formaldehyde, and a +44 u neutral gain/-30 u neutral loss MS3 scan is shown to efficiently detect reactive carboxonium and carbosulfonium ions. Transacetalization with either carboxonium or carbosulfonium ions provides a route to 1,3-oxathiolanes and analogs alkylated selectively either at the sulfur or oxygen atom.     

Covalent modification of gaseous peptide ions with N-hydroxysuccinimide ester reagent ions

Covalent modification of primary amine groups in multiply protonated or deprotonated polypeptides in the gas phase via ion/ion reactions is demonstrated using N-hydroxysuccinimide (NHS) esters as the modifying reagents. During the ion/ion reaction, the peptide analyte ions and the NHS or sulfo-NHS based reagent form a long-lived complex, which is a prerequisite for the covalent modification chemistry to occur. Ion activation of the peptide-reagent complex results in a neutral NHS or sulfo-NHS molecule loss, which is a characteristic signature of covalent modification. As the NHS or sulfo-NHS group leaves, an amide bond is formed between a free, unprotonated, primary amine group of a lysine side chain in the peptide and the carboxyl group in the reagent. Subsequent activation of the NHS or sulfo-NHS loss product ions results in sequence informative fragment ions containing the modification. The N-terminus primary amine group does not make a significant contribution to the modification process; this behavior has also been observed in solution phase reactions. The ability to covalently modify primary amine groups in the gas phase with N-hydroxysuccinimide reagents opens up the possibility of attaching a wide range of chemical groups to gaseous peptides and proteins and also for selectively modifying other analytes containing free primary amine groups.     

Stable aziridinium salts of oxalic and 2,5-dihydro-4,5,5-trimethyl-2-oxo-5-furancarboxylic acids

Conclusions Stable salts of aziridine, 2-methylaziridine, and 2,2-dimethylaziridine with the oxalic and 2,5-dihydro-4,5,5~trimethyl-2-oxo-5-furancarboxylic acids were obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 192–194, January, 1983.     

Alkylation of benzyl chloride by gaseous carbenium ions

The alkylation of benzyl chloride has been studied in the gas phase using radiolytically formed carbenium ions as the charged reagents. The intramolecular selectivity of the electrophilic attack, deduced from the composition of the neutral products, is characterized by the comparable reactivity of the aromatic ring and of the halogen atom of the substrate toward the gaseous cations. As to ring alkylation, the reactivity of the ortho positions of benzyl chloride is considerably lower than those of chlorobenzene. The results are compared with pertinent mass-spectrometric data, and discussed in connection with existing models of gas phase aromatic substitution by charged electrophiles.     

Stereochemical preferences in 4-center syn-eliminations from gaseous ions

Concerted unimolecular eliminations from ionized sec-alkyl aryl ethers (ROAr (+*)) display a preference for producing double bonds with trans geometry. This preference can be assessed quantitatively, provided that a regioselective variant can be found. Expulsion of neutral alkenes via syn-elimination to give ionized ArOH does not exhibit a pronounced preference with regard to the direction of elimination. By contrast, ionized 2-hexyl p-trifluoromethylphenyl ether eliminates neutral ArOH regioselectively, giving ionized 2-hexenes rather than ionized 1-hexene. Vicinally monodeuterated 2-hexyl and 3-hexyl ethers were prepared as pure diastereomers. Metastable ion decompositions of their gaseous radical cations are compared over two different time windows. The regioselectivity for the 2-hexyl ether allows the geometric preference for the double bonds to be estimated based on the difference between the erythro and threo monodeuterated diastereomers ( trans/ cis = 2.0 for producing ionized 2-hexene from parent ions with the lowest internal energies). The 3-hexyl ethers and ionized 2- and 3-phenoxyoctanes also undergo stereoselective elimination but give experimental values that reflect their lack of regioselectivity. Examination of erythro/ threo combinations shows that GC/MS/MS has the ability to quantitate stereochemistry in mixtures containing both positional and stereoisomers.     

An iterative approach to novel polyamines via nucleophilic ring-opening of aziridinium ions with beta-amino alcohols

An iterative procedure for the synthesis of a novel class of synthetic polyamines has been developed, utilising the regioselective ring-opening of aziridinium ion intermediates; facile N-allyl deprotection of intermediate polyamines allows the rapid construction of high molecular weight, stereochemically defined compounds in a convergent manner.     

Assessing the rates of ring-opening of aziridinium and azetidinium ions: a dramatic ring size effect

Rates for the ring-opening of aziridinium and azetidinium ions by DMAP were measured. The four-membered ring appears to be ca. 17,000 times less reactive compared to the three-membered ring but is still highly relevant from a synthetic viewpoint. The electrophilicity of these strained ammonium ions is measured for the first time.     

Reactivity and infrared spectroscopy of gaseous hydrated trivalent metal ions

Hydrated trivalent rare earth metal ions containing yttrium and all naturally abundant lanthanide metals are formed using electrospray ionization, and the structures and reactivities of these ions containing 17-21 water molecules are probed using blackbody infrared radiative dissociation (BIRD) and infrared action spectroscopy. With the low-energy activation conditions of BIRD, there is an abrupt transition in the dissociation pathway from the exclusive loss of a single neutral water molecule to the exclusive loss of a small protonated water cluster via a charge-separation process. This transition occurs over a narrow range of cluster sizes that differs by only a few water molecules for each metal ion. The effective turnover size at which these two dissociation rates become equal depends on metal ion identity and is poorly correlated with the third ionization energies of the isolated metals but is well correlated with the hydrolysis constants of the trivalent metal ions in bulk aqueous solution. Infrared action spectra of these ions at cluster sizes near the turnover size are largely independent of the specific identity of the trivalent metal ion, suggesting that any differences in the structures of the ions present in our experiment are subtle.     

Reactions of gaseous ions. I. Methane and ethylene

At elevated pressures in a mass spectrometer ion source reactions occur between certain ions and the neutral species present. We have studied the various secondary ions formed in methane and ethylene at elevated pressures and have determined the reactions by which they are formed and the rates of these reactions. The rates are all extremely fast. The reaction rates have been treated by classical collision theory and it has been shown that to a fair approximation the cross-sections and reaction rate constants can be predicted from a simple balance of rotational and polarization forces. [Reprinted from J. Am. Chem. Soc. 1957; 79: 2419.] Copyright 1957 by the American Chemical Society and reprinted by permission of the copyright owner.