Polar [4+2+] diels-alder cycloaddition to nitrilium and immonium ions in the gas phase: Applications of multiple stage mass spectrometry in a pentaquadrupole instrument

Multiple stage MS² and MS³ mass spectrometric experiments, performed using a pentaquadrupole instrument, are employed to explore the gas-phase ion-molecule chemistry of several nitrilium [R-C≡N⁺-H (1), R-C≡N⁺-CH₃ (2), and H-C≡N⁺-C₂H₅ (3)] as well as immonium ions RR¹C=N⁺R²R³ (4) with the neutral diene isoprene. Polar [4+2⁺] Diels-Alder cycloaddition is observed for nitrilium ions when the energy gap between the lowest unoccupied molecular orbital (LUMO) of the ion and the highest occupied molecular orbital (HOMO) of the isoprene is small and the competing proton transfer reaction is endothermic. Thus, C-protonated methyl isonitrile H-C≡N⁺-CH₃ (2a) and its higher homolog H-C≡N⁺-C₂H₅ (3a) form abundant [4+2⁺] cycloadducts with isoprene, but several protonated nitriles 1 do not; instead they show exothermic proton transfer as the main ion-molecule reaction. Replacement of the methyne hydrogen in 2a by a methyl, ethyl, or phenyl group (2b–d) raises the LUMO-HOMO gap, which greatly decreases the total yield of ion-molecule products and precludes cycloaddition. On the other hand, the electron-withdrawing acetyl and bromine substituents in 2e and 2f substantially lower the LUMO energy of the ions and cycloaddition reaction occurs readily. The simplest member of the immonium ion series, CH₂=NH ₂ ⁺ (4a), reacts readily by cycloaddition, whereas alkyl substitution on either the carbon or nitrogen (4b–f) dramatically lowers the overall reactivity, which substantially decreases or even precludes cycloaddition. In strong contrast, the N-phenyl (4g) and N-acetyl (4h) ions and the N-vinyl-substituted immonium ion, N-protonated 2-aza-butadiene (4i), react extensively with isoprene, mainly by [4+2⁺] cycloaddition. However, the isomeric C-vinyl-substituted ion (4j) displays only modest reactivity in both the proton-transfer and the cycloaddition channels. Collision-induced dissociation (CID) of the cycloadducts performed by on-line MS³ experiments demonstrates that they are covalently bound and supports their assignments as cycloaddition products. Retro Diels-Alder fragmentation is a major process for cycloadducts of both the immonium and the nitrilium ions, but other fragmentation processes also are observed. The cycloadduct of 4a with butadiene displays CID fragmentation identical to that of the authentic ion produced by protonation of 1,2,3,6-tetrahydropyridine, which thus strengthens the [4+2⁺] cycloaddition proposal. AM1 calculations also support the formation of the [4+2⁺] cycloadducts, which are shown in several cases to be much more stable than the products of simple addition, that is, the ring-open isomers.     

Gas phase ion chemistry of charged silver(I) adenine ions via multistage mass spectrometry experiments and DFT calculations

Electrospray ionization (ESI) of solutions containing adenine and AgNO(3) yields polymeric [Ad(x)+ Ag(y)-zH]((y-z)+) species. Density functional theory (DFT) calculations have been used to examine potential structures for several of the smaller ions while multistage mass spectrometry experiments have been used to probe their unimolecular reactivity (via collision-induced dissociation (CID)) and bimolecular reactivity (via ion-molecule reactions with the neutral reagents acetonitrile, methanol, butylamine and pyridine). DFT calculations of neutral adenine tautomers and their silver ion adducts provide insights into the binding modes of adenine. We find that the most stable [Ad + Ag](+) ion does not correspond to the most stable neutral adenine tautomer, consistent with previous studies that have shown that transition metal ions can stabilize rare tautomeric forms of nucleobases. Both the charge and the stoichiometry of the [Ad(x)+ Ag(y)-zH]((y-z)+) complexes play pivotal roles in directing the types of fragmentation and ion-molecule reactions observed. Thus, [Ad(2)+ Ag(2)](2+) is observed to dissociate to [Ad + Ag](+) and to react with butylamine via proton transfer, while [Ad(2)+ Ag(2)- H](+) fragments via loss of neutral adenine to form the [Ad + Ag(2)- H](+) ion and does not undergo proton transfer to butylamine. DFT calculations on several isomeric [Ad(2)+ Ag(2)](2+) ions suggest that planar centrosymmetric cations, in which two adjacent silver atoms are bridged by two N7H adenine tautomers via N(3),N(9)-bidentate interactions, are the most stable. The [Ad + Ag(2)-H](+) ion adds two neutral reagents in ion-molecule reactions, consistent with the presence of two vacant coordination sites. It undergoes a silver atom loss to form the [Ad + Ag - H](+) radical cation, which in turn fragments quite differently to the even electron [Ad + Ag](+) ion. Several other pairs of radical cation/even electron adenine-silver complexes were also found to undergo different fragmentation reactions.     

Gas-phase polar [4+ + 2] cycloaddition with ethyl vinyl ether: a structurally diagnostic ion-molecule reaction for 2-azabutadienyl cations

The intrinsic reactivity of eight gaseous, mass-selected 2-azabutadienyl cations toward polar [4(+) + 2] cycloaddition with ethyl vinyl ether has been investigated by pentaquadrupole mass spectrometric experiments. Cycloaddition occurs readily for all the ions and, with the only exception of those from the N-acyl 2-azabutadienyl cations (N-acyliminium ions), the cycloadducts are found to dissociate readily upon collision activation (CID) both by retro-Diels-Alder reaction and by a characteristic loss of an ethanol (46u) neutral molecule. Ethanol loss from the intact polar [4(+) + 2] cycloadduct functions therefore as a structurally diagnostic test: 72 u neutral gain followed by 46 u neutral loss, i.e., as a combined ion-molecule reaction plus CID 'signature' for N-H, N-alkyl and N-aryl 2-azabutadienyl cations. The two N-acyliminium ions tested are exceptional as they form intact cycloadducts with ethyl vinyl ether which dissociate exclusively by the retro-Diels-Alder pathway.     

Ion-molecule reactions and collision-activated dissociation of C4H 4 +. isomers: A case study in the use of the MS3 capabilities of a pentaquadrupole mass spectrometer

Isomeric C₄H ₄ ^+. radical cations vinylacetylene (a), butatriene (b), methylene cyclopropene (c), and the nonaromatic cyclobutadiene (d), generated, respectively, from the neutral precursors 3-butyn-1-ol (1), 1,4-dichloro-2-butyne (2), benzene (3), and 7,8-benzotricyclo [4.2.2.0^2,5]deca-3,7,9-triene (4), undergo diagnostically different ion-molecule reactions with allene, isoprene, furan, and thiophene. It is speculated that adducts are generated by [2 + 2] cycloadditions with the first reagent and [4 + 2] Dials-Alder cycloadditions with isoprene, furan, and thiophene. The initially formed cycloaddition adducts fragment rapidly, isomerize, or undergo further addition of neutral reagent to yield a complex set of products. With a pentaquadrupole mass spectrometer, MS³ experiments that employ three stages of ion mass analysis are used to help elucidate the ion-molecule reactions and to distinguish the isomeric C⁴H ₄ ^+. ions. Among these experiments, the reaction intermediate spectrum reveals the nature of the intermediates connecting the reactant to a selected product while the sequential product spectrum provides mechanistic and structural information on the adducts and other ion-molecule products. The unique combination of ion-molecule reactions with collision-activated dissociation employed here provides valuable information on the chemistry of ionized cyclobutadiene, including its proclivity to undergo [2 + 2] and [4 + 2] cyc1oadditions.     

Generation of alkoxide anions from a series of aliphatic diols and alcohols and their ion-molecule reactions with carbon dioxide in the gas phase

Alkoxide anions, [M-H](-) from a series of aliphatic diols and alcohols are generated in the source under negative ion electrospray ionisation conditions by cone-voltage fragmentation of the corresponding [M + F](-) ions. The collision-induced dissociation (CID) spectra of [M-H](-) ions consist of [M-H-2H](-) ions, in addition to the other characteristic fragment ions, and the relative abundance of [M-H-2H(-) ions among the series of diols varies as a function of chain length that could be explained based on their stabilities through intramolecular hydrogen bonding. The reactivity of alkoxide anions is studied through ion-molecule reactions with CO(2) in the collision cell of a triple quadrupole mass spectrometer. All the alkoxide anions reacted with CO(2) and formed corresponding carbonate anions, [M-H + CO(2)](-) ions. The reactivity of alkoxide anions within the series of diols also reflected the stability of their [M-H](-) ions.     

Formal fusion of a pyrrole ring onto 2-pyridyl and 2-pyrimidyl cations: one-step gas-phase synthesis of indolizine and its derivatives

Two ortho-hetarynium ions, the 2-pyridyl and 2-pyrimidyl cations, react promptly with 1,3-dienes in the gas phase by annulation, formally by fusion, onto the ions of a pyrrole ring. This novel reaction proceeds through an initial polar [4 + 2+] cycloaddition across the C[triple bond]N+ bond, followed by fast ring opening, a [1,4-H] shift, and finally a recyclization that results in a contraction of a six- to a five-membered ring and dissociation by the loss of a methyl radical. For the 2-pyridyl cation, this reaction yields ionized indolizines (pyrrolo[1,2-a]pyridines), while for the 2-pyrimidyl cation, it gives ionized pyrrolo[1,2-a]pyrimidines. The annulation reaction, performed in the rf-only collision quadrupole of a pentaquadrupole (QqQqQ) mass spectrometer, occurs readily with both 1,3-butadiene and isoprene, and is thermodynamically and kinetically favored as predicted by ab initio calculations. Ortho-hetarynium ions and 1,3-dienes provide, therefore, the two building blocks for the efficient one-step gas-phase synthesis of ionized bicyclic pyrrolo[1,2-a]pyridine (indolizine) and pyrrolo[1,2-a]pyrimidine, as well as their analogues and derivatives.     

An investigation of site-selective gas-phase reactions of amino alcohols with dimethyl ether ions

The reactions of dimethyl ether ions with neutral amino alcohols were examined in both a quadrupole ion trap mass spectrometer and a triple quadrupole mass spectrometer. These ion-molecule reactions produced two types of ions: the protonated species [M+l]⁺ and a more complex product at [M+13]⁺. The abundance of the [M+13]⁺ ions relative to that of the [M+1]⁺ ions decreases with increasing formal interfunctional distance. Multistage collision-activated dissociation techniques were used to characterize the [M+13]⁺ product ions, their reactivities, and the mechanisms for their formation and dissociation. In addition, molecular semiempirical calculation methods were used to probe the thermochemistry of these reactions. Reaction at the amino alcohol nitrogen site is favored, and the resulting [M+13]⁺ addition products may cyclize for additional stabilization. Comparisons were made among the behavior of related compounds, such as alcohols, diols, amines, and diamines. The alcohols reacted only to form the protonated species, but the diols, amines, and diamines all formed significant amounts of [M+13]⁺ ions or related dissociation products.     

Dissociation of disulfide‐intact somatostatin ions: the roles of ion type and dissociation method

The dissociation chemistry of somatostatin‐14 was examined using various tandem mass spectrometry techniques including low‐energy beam‐type and ion trap collision‐induced dissociation (CID) of protonated and deprotonated forms of the peptide, CID of peptide‐gold complexes, and electron transfer dissociation (ETD) of cations. Most of the sequence of somatostatin‐14 is present within a loop defined by the disulfide linkage between Cys‐3 and Cys‐14. The generation of readily interpretable sequence‐related ions from within the loop requires the cleavage of at least one of the bonds of the disulfide linkage and the cleavage of one polypeptide backbone bond. CID of the protonated forms of somatostatin did not appear to give rise to an appreciable degree of dissociation of the disulfide linkage. Sequential fragmentation via multiple alternative pathways tended to generate very complex spectra. CID of the anions proceeded through CH₂? S cleavages extensively but relatively few structurally diagnostic ions were generated. The incorporation of Au(I) into the molecule via ion/ion reactions followed by CID gave rise to many structurally relevant dissociation products, particularly for the [M+Au+H]²⁺ species. The products were generated by a combination of S? S bond cleavage and amide bond cleavage. ETD of the [M+3H]³⁺ ion generated rich sequence information, as did CID of the electron transfer products that did not fragment directly upon electron transfer. The electron transfer results suggest that both the S? S bond and an N? C_α bond can be cleaved following a single electron transfer reaction. Copyright © 2009 John Wiley & Sons, Ltd.     

Formal gas-phase polar [4 + 1+] cycloaddition of ionized methylene to alpha-dicarbonyl compounds: synthesis of 2-unsubstituted 1,3-dioxoles

Ion/molecule reactions of +CH2OCH2. with alpha-dicarbonyl compounds were performed via pentaquadrupole mass spectrometry. Besides the previously known [3+ + 2] 1,3-cycloaddition reaction that forms cyclic 1,3-dioxonium ions, an unprecedented reaction proceeding formally by [4 + 1+] cycloaddition of ionized methylene (CH2+.) to the alpha-dicarbonyl compounds occurs competitively, leading to the gas-phase synthesis of several ionized 2-unsubstituted 1,3-dioxoles. This novel cycloaddition reaction may therefore be added to the set of methods available for the synthesis of 1,3-dioxoles.     

Exploring the intrinsic polar [4 + 2+] cycloaddition reactivity of gaseous carbosulfonium and carboxonium ions

Gas‐phase reactions of model carbosulfonium ions (CH₃‐S⁺ = CH_2; CH₃CH₂‐S⁺ = CH₂ and Ph‐S⁺ = CH₂) and an O‐analogue carboxonium ion (CH₃‐O⁺ = CH₂) with acyclic (isoprene, 1,3‐butadiene, methyl vinyl ketone) and cyclic (1,3‐cyclohexadiene, thiophene, furan) conjugated dienes were systematically investigated by pentaquadrupole mass spectrometry. As corroborated by B3LYP/6‐311 G(d,p) calculations, the carbosulfonium ions first react at large extents with the dienes forming adducts via simple addition. The nascent adducts, depending on their stability and internal energy, react further via two competitive channels: (1) in reactions with acyclic dienes via cyclization that yields formally [4 + 2⁺] cycloadducts, or (2) in reactions with the cyclic dienes via dissociation by HSR loss that yields methylenation (net CH⁺ transfer) products. In great contrast to its S‐analogues, CH₃‐O⁺ = CH₂ (as well as C₂H₅‐O⁺ = CH₂ and Ph‐O⁺ = CH₂ in reactions with isoprene) forms little or no adduct and proton transfer is the dominant reaction channel. Isomerization to more acidic protonated aldehydes in the course of reaction seems to be the most plausible cause of the contrasting reactivity of carboxonium ions. The CH₂ = CH‐O⁺ = CH₂ ion forms an abundant [4 + 2⁺] cycloadduct with isoprene, but similar to the behavior of such α,β‐unsaturated carboxonium ions in solution, seems to occur across the C = C bond. Copyright © 2012 John Wiley & Sons, Ltd.     

Mass spectrometric investigation of noncovalent complexation between a tetratosylated resorcarene and alkyl ammonium ions

Noncovalent complexation between tetratosylated tetraethyl resorcarene (1) and primary, secondary, and tertiary alkyl ammonium ions (mMe, dMe, tMe, mEt, dEt, tEt, dBu, and dHex) was studied by electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. Interactions of the noncovalent complexes were investigated by means of competition experiments, collision-induced dissociation (CID) experiments, ion-molecule reactions with tripropylamine and gas phase H/D-exchange reactions with deuteroammonia. Gas phase ion-molecule reactions gave especially valuable information about the structure and properties of the complexes. Resorcarene 1 formed relatively stable 1:1 complexes with all aliphatic alkyl ammonium ions. Steric properties of the alkyl ammonium ions and proton affinities of the conjugate amines noticeably affected the complexation properties, indicating the importance of hydrogen bonding in these complexes. According to the competition experiments, the thermodynamically most stable host-guest complexes were formed with alkyl ammonium ions that were most substituted and had the longest alkyl chains. In CID experiments, release of an intact free guest ion or dissociation of the host was observed to depend on the proton affinity of the amine and the strength of the hydrogen bond that was formed. In ion-molecule reactions with tripropylamine, a guest exchange reaction occurred with all alkyl ammonium ion complexes with reaction rates mostly dependent on the steric properties of the original guest ion. In H/D-exchange reactions the N-H hydrogen atoms of the guest ion were exchanged with deuterium, whereas the resorcinol hydrogen atoms remained unchanged.     

Meerwein reaction of phosphonium ions with epoxides and thioepoxides in the gas phase

Phosphonium ions are shown to undergo a gas-phase Meerwein reaction in which epoxides (or thioepoxides) undergo three-to-five-membered ring expansion to yield dioxaphospholanium (or oxathiophospholanium) ion products. When the association reaction is followed by collision-induced dissociation (CID), the oxirane (or thiirane) is eliminated, making this ion molecule reaction/CID sequence a good method of net oxygen-by-sulfur replacement in the phosphonium ions. This replacement results in a characteristic mass shift of 16 units and provides evidence for the cyclic nature of the gas-phase Meerwein product ions, while improving selectivity for phosphonium ion detection. This reaction sequence also constitutes a gas-phase route to convert phosphonium ions into their sulfur analogs. Phosphonium and related ions are important targets since they are commonly and readily formed in mass spectrometric analysis upon dissociative electron ionization of organophosphorous esters. The Meerwein reaction should provide a new and very useful method of recognizing compounds that yield these ions, which includes a number of chemical warfare agents. The Meerwein reaction proceeds by phosphonium ion addition to the sulfur or oxygen center, followed by intramolecular nucleophilic attack with ring expansion to yield the 1,3,2-dioxaphospholanium or 1,3,2-oxathiophospholanium ion. Product ion structures were investigated by CID tandem mass spectrometry (MS(2)) experiments and corroborated by DFT/HF calculations.     

Measurement of collision-induced dissociation rates for tantalum oxide ions in a quadrupole ion trap

A study of factors influencing the collision-induced dissociation (CID) rate of strongly bound diatomic ions effected via resonance excitation in a quadrupole ion trap is presented. From these studies, an approach to measuring the CID rates is described wherein product ion recovery is optimized and the effect of competitive processes (e.g., parent ion ejection and product ion reactions) on rate measurements are prevented from influencing rate measurements. Tantalum oxide ions (dissociation ENERGY = 8.2 eV), used as a model system, were formed via reactions of glow discharge generated Ta⁺ ions with residual gases in the ion trap. Neon (0.5 mtorr) was found to be a more favorable target gas for the dissociation of TaO⁺ than He and Ar, but collisional activation of TaO⁺ ions in neon during ion isolation by mass selective instability necessitated ion cooling prior to dissociation. A 25 ms delay time at q_z = 0.2 allowed for kinetic cooling of stored TaO⁺ ions and enabled precise dissociation rate measurements to be made. CID of TaO⁺ was determined to be most efficient at q_z = 0.67 (226 kHz for m/z 197). Suitable resonance excitation voltages and times ranged from 0.56 to 1.2 V_p-p and 1 to 68 ms, respectively. Under these conditions, measurement of rates approaching 80 s⁻¹ for the dissociation of TaO⁺ could be made without significant complications associated with competing processes, such as ion ejection.     

Mass spectral study of alkali-cationized Boc-carbo-beta3-peptides by electrospray tandem mass spectrometry

Electrospray tandem mass spectrometry was used to study the dissociation reactions of [M+Cat]+ (Cat = Na+ and Li+) of Boc-carbo-beta3-peptides. The collision-induced dissociation (CID) spectra of [M+Cat-Boc]+ of these peptides are found to be significantly different from those of [M+H-Boc]+ ions. The spectra are more informative and display both C- and N-terminus metallated ions in addition to characteristic fragment ions of the carbohydrate moiety. Based on the fragmentations observed in the CID spectra of the [M+Cat-Boc]+ ions, it is suggested that the dissociation involves complexes in which the metal ion is coordinated in a multidentate arrangement involving the carbonyl oxygen atoms. The CID spectra of [M+Cat-Boc]+ ions of the peptide acids show an abundant N-terminal rearrangement ion [b(n)+17+Cat]+ which is absent for esters. Further, two pairs of positionally isomeric Boc-carbo-beta3-peptide acids, Boc-NH-Caa(S)-beta-hGly-OH (11) and Boc-NH-beta-hGly-Caa(S)-OH (12), and [Boc-NH-Caa(S)-beta-hGly-Caa(S)-beta-hGly-OH] (13) and [Boc-NH-beta-hGly-Caa(S)-beta-hGly-Caa(S)-OH] (14), were differentiated by the CID of [M+Cat-Boc]+ ions. The CID spectra of compounds 11 and 13 are significantly different from those of 12 and 14, respectively. The abundance of [b(n)+17+Cat]+ ions is higher for peptide acids 12 and 14 with a sugar group at the C-terminus when compared to 11 and 13 which contain a sugar moiety at the N-terminus. The observed differences between the CID spectra of these isomeric peptides are attributed to the difference in the preferential site of metal ion binding and also on the structure of the cyclic intermediate involved in the formation of the rearrangement ion.     

Transformation of Phosphaalkynes into 1H- and 2H-Phosphirenes1

Abstract

The 2H-phosphirene 4 is synthesized from the spirocyclic 3H-1,2,4-diazaphosphole 1 by low temperature photolysis. The isomeric 1H-phosphirenes 7 are formed by a [2+1]-cycloaddition process of chlorocarbenes, generated from diazirines. onto the triple bond of phosphaalkynes. When the 1-chlon-1H-phosphirenes 7 are allowed to react with a series of nucleophiles substitution occurs yielding the 1H-phosphirenes 9, 11 and 12. The existance of a phosphirenium cations, for instance 13 is discussed.     

Selective ion-molecule reactions of lactams with dimethyl ether ions

The ion-molecule reactions of dimethyl ether ions CH₃OCH₃ ⁺ and (CH₃OCH₃)H⁺, and four- to seven-membered ring lactams with methyl substituents in various positions were characterized by using a quadrupole ion trap mass spectrometer and a triple-quadrupole mass spectrometer. In both instruments, the lactams were protonated by dimethyl ether ions and formed various combinations of [M + 13] ⁺, [M + 15] ⁺, and [M + 45] ⁺ adduct ions, as well as unusual [M + 3] ⁺ and [M + 16] ⁺ adduct ions. An additional [M + 47] ⁺ adduct ion was formed in the conventional chemical ionization source of the triple-quadrupole mass spectrometer. The product ions were isolated and collisionally activated in the quadrupole ion trap to understand formation pathways, structures, and characteristic dissociation pathways. Sequential activation experiments were performed to elucidate fragment ion structures and stepwise dissociation sequences. Protonated lactams dissociate by loss of water, ammonia, or methylamine; ammonia and carbon monoxide; and water and ammonia or methylamine. The [M + 16] ⁺ products, which are identified as protonated lactone structures, are only formed by those lactams that do not have an N-methyl substituent. The ion-molecule reactions of dimethyl ether ions with lactams were compared with those of analogous amides and lactones.     

Discrimination Between Peptide O-Sulfo- and O-Phosphotyrosine Residues by Negative Ion Mode Electrospray Tandem Mass Spectrometry

Unambiguous differentiation between isobaric sulfated and phosphorylated tyrosine residues (sTyr and pTyr) of proteins by mass spectrometry is challenging, even using high resolution mass spectrometers. Here we show that upon negative ion mode collision-induced dissociation (CID), pTyr- and sTyr-containing peptides exhibit entirely different modification-specific fragmentation patterns leading to a rapid discrimination between the isobaric covalent modifications using the tandem mass spectral data. This study reveals that the ratio between the relative abundances of [M-H-80](-) and [M-H-98](-) fragment ions in ion-trap CID and higher energy collision dissociation (HCD) spectra of singly deprotonated +80 Da Tyr-peptides can be used as a reliable indication of the Tyr modification group nature. For multiply deprotonated +80 Da Tyr-peptides, CID spectra of sTyr- and pTyr-containing sequences can be readily distinguished based on the presence/absence of the [M-nH-79]((n-1)-) and [M-nH-79-NL]((n-1)-) (n=2, 3) fragment ions (NL=neutral loss).     

气相中卤代苯离子-分子反应产物的串联质谱研究

应用碰撞诱导解离技术研究了氯代苯、溴代苯和碘代苯离子-分子反应产物的碎裂反应特性,与联苯的分子离子和质子化溴代联苯的碰撞诱导解离谱比较获得了产物离子的结构信息.     

Mono and double polar [4 + 2(+)] Diels-Alder cycloaddition of acylium ions with O-heterodienes

Gas-phase reactions of acylium ions with alpha,beta-unsaturated carbonyl compounds were investigated using pentaquadrupole multiple-stage mass spectrometry. With acrolein and metacrolein, CH(3)-C(+)(double bond)O, CH(2)(double bond)CH-C(+)(double bond)O, C(6)H(5)-C(+)(double bond)O, and (CH(3))(2)N-C(+)(double bond)O react to variable extents by mono and double polar [4 + 2(+)] Diels-Alder cycloaddition. With ethyl vinyl ketone, CH(3)-C(+)(double bond)O reacts exclusively by proton transfer and C(6)H(5)-C(+)(double bond)O forms only the mono cycloadduct whereas CH(2)(double bond)CH-C(+)(double bond)O and (CH(3))(2)N-C(+)(double bond)O reacts to great extents by mono and double cycloaddition. The positively charged acylium ions are activated O-heterodienophiles, and mono cycloaddition occurs readily across their C(+)(double bond)O bonds to form resonance-stabilized 1,3-dioxinylium ions which, upon collisional activation, dissociate predominantly by retro-addition. The mono cycloadducts are also dienophiles activated by resonance-stabilized and chemically inert 1,3-dioxonium ion groups, hence they undergo a second cycloaddition across their polarized C(double bond)C ring double bonds. (18)O labeling and characteristic dissociations displayed by the double cycloadducts indicate the site and regioselectivity of double cycloaddition, which are corroborated by Becke3LYP/6-311++G(d,p) calculations. Most double cycloadducts dissociate by the loss of a RCO(2)COR(1) molecule and by a pathway that reforms the acylium ion directly. The double cycloadduct of the thioacylium ion (CH(3))(2)N-C(+)(double bond)S with acrolein dissociates to (CH(3))(2)N-C(+)(double bond)O in a sulfur-by-oxygen replacement process intermediated by the cyclic monoadduct. The double cycloaddition can be viewed as a charge-remote type of polar [4 + 2(+)] Diels-Alder cycloaddition reaction.     

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.