Diastereoselective Synthesis of Rotationally Restricted Chiral Phenylpyridines via Intramolecular Cascade Cyclization of N-Acyliminium Ions Containing α-Amino Acid Residues

A series of chiral phenylpyridines possessing a fused chiral bridge were synthesized diastereoselectively via cascade cyclizations, where N-acyliminium ions including an enantiopure α-amino acid residue were involved. The absolute configuration of the synthesized phenylpyridines was identified unambiguously by using nuclear Overhauser effect difference and circular dichroism (CD) measurements on the basis of literature methods.

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endo-Mode cyclizations of vinylogous N-acyliminium ions as a route to the synthesis of condensed thiazolidines

endo-Mode cyclizations of vinylogous N-acyliminium ions incorporating heteroatom-based nucleophiles have been examined as a route to the synthesis of condensed thiazolidines. The scope of these reactions and stereochemical outcome are discussed and explained using quantum chemical calculations.     

Fragmentation of negative ions from N‐linked carbohydrates,Part 4. Fragmentation of complex glycans lacking substitution on the 6‐antenna

Negative ion CID spectra of N‐linked glycans released from glycoproteins contain many ions that are diagnostic for specific structural features such as the detailed arrangement of antennae and the location of fucose residues. Identification of such ions requires reference glycans that are often difficult to acquire in a pure state. The recent acquisition of a sample of N‐glycans from a patient lacking the enzyme N‐acetylglucosaminyltransferase‐2 provided an opportunity to investigate fragmentation of glycans lacking a 6‐antenna. These glycans contained one or two galactose‐N‐acetylglucosamine‐chains attached to the 3‐linked mannose residue of the trimannosyl‐chitobiose core with and without fucose substitution. The spectra from the patient sample clearly defined the antenna distribution and showed striking differences from the spectra of isomeric compounds obtained from normal subjects. Furthermore, they provided additional information on previously identified antenna‐specific fragment ions and indicated the presence of additional ions that were diagnostic of fucose substitution. Glycans obtained from such enzyme‐deficient patients can, thus, be a valuable way of obtaining spectra of specific isomers in a relatively pure state for interpretation of mass spectra. Copyright © 2010 John Wiley & Sons, Ltd.     

Combining α-amidoalkylation reactions of N-acyliminium ions with ring-closing metathesis: access to versatile novel isoindolones spirocyclic compounds

A novel approach to diversely spirocyclic isoindoles has been developed by using N-acyliminium/ring-closing metathesis strategy. Spirocyclization precursors, diolefinic, and enyne spiro-fused-isoindole derivatives have been obtained by a regioselective reduction of the spiro-imide compounds, followed by the allylation of the N-acyliminium intermediates (generated from the acetoxylactam compounds). Ruthenium catalyzed ring-closing metathesis of the above unsaturated derivatives provided novel spiroisoindoles.     

TiCl4-promoted addition of nucleophiles to open chain α-amidoalkylphenyl sulfones

Linear α-amidoalkylphenyl sulfones are converted into the corresponding N-acyliminium ions by treatment with TiCl₄ at low temperature and then made to react with different nucleophiles such as allyltrimethylsilane, silyl ketene acetal, anisole and thiophene.     

Negative-ion mass spectra of some N-mesyl derivatives of o-(cycloalk-2-enyl)-, o-(cycloalk-1-enyl)-, o-(pent-2-enyl)-, o-dibromopentylanilines and (α-bromoalkyl)indolines

The formation and fragmentation of negative ions of some N-(methylsulfonyl)anilines upon resonance electron capture have been studied. The formation of long-living molecular ions is due to the presence of the mesyl groups in the molecules. The difference in negative-ion mass spectra of isomeric N-(methylsulfonyl)anilines has been revealed.     

Immobilization of Two Azacrown Ethers on Chitosan: Evaluation of Selective Extraction Ability Toward Cu(II) and Ni(II)

Two Schiff base-type chitosan-azacrown ethers were prepared by a reaction of chitosan (CTS) with N-(4′-formylphenyl)aza-crown ethers, and they were converted to secondary-amino derivatives by the reduction of CTS-azacrown ethers with sodium borohydride. Their structures were confirmed by elemental analysis, infrared spectra and thermogravimetric analysis. The ability of these adsorbents to extract Cu(II) and Ni(II) ions from water by a solid-liquid extraction process was studied. The effects of adsorbent amount, contact time and pH on the adsorption of CTS-azacrown ethers were investigated. The extraction results showed that CTS-azacrown ethers had good sorption capacities for Cu(II) ions in the coexistence of Ni(II) ions.     

Sonogashira/N-acyliminium ion aromatic π-cyclisation processes: access to tetra- and pentacyclic lactams

Application of the Sonogashira reaction of N-alkynylimides with 2-iodophenol or 2-iodo-N-tosylaniline affords 2-(N-alkylimino)-benzofurans and indoles in good yield. Selective partial reduction of the latter followed by treatment with TsOH generates N-acyliminium ions, which cyclise to afford tetra- and pentacyclic lactams in good yield. The latter are reduced to the analogous cyclic amines by BH₃.     

The synthetic versatility of alkoxycarbonyl- and hydroxymethyl-piperazine-2,5-diones

Alkoxycarbonylpiperazine-2,5-diones are versatile precursors for the α-functionalisation of piperazine-2,5-diones. The alkoxycarbonyl group activates the α-carbon position to alkylation reactions and this provides a mild and selective method for the extension of the carbon framework of piperazine-2,5-diones. In addition, the alkoxycarbonyl group can be converted to the carboxy group, which in turn can be ‘deleted’ or manipulated for the installation of carbon and/or heteroatom substituents where desired, the latter via N-acyliminium chemistry. We also demonstrate that hydroxymethylpiperazine-2,5-diones complement carboxypiperazinediones as precursors for the generation of N-acyliminium ions.     

Travelling‐wave ion mobility and negative ion fragmentation of high‐mannose N‐glycans

The isomeric structure of high‐mannose N‐glycans can significantly impact biological recognition events. Here, the utility of travelling‐wave ion mobility mass spectrometry for isomer separation of high‐mannose N‐glycans is investigated. Negative ion fragmentation using collision‐induced dissociation gave more informative spectra than positive ion spectra with mass‐different fragment ions characterizing many of the isomers. Isomer separation by ion mobility in both ionization modes was generally limited, with the arrival time distributions (ATD) often showing little sign of isomers. However, isomers could be partially resolved by plotting extracted fragment ATDs of the diagnostic fragment ions from the negative ion spectra, and the fragmentation spectra of the isomers could be extracted by using ions from limited areas of the ATD peak. In some cases, asymmetric ATDs were observed, but no isomers could be detected by fragmentation. In these cases, it was assumed that conformers or anomers were being separated. Collision cross sections of the isomers in positive and negative fragmentation mode were estimated from travelling‐wave ion mobility mass spectrometry data using dextran glycans as calibrant. More complete collision cross section data were achieved in negative ion mode by utilizing the diagnostic fragment ions. Examples of isomer separations are shown for N‐glycans released from the well‐characterized glycoproteins chicken ovalbumin, porcine thyroglobulin and gp120 from the human immunodeficiency virus. In addition to the cross‐sectional data, details of the negative ion collision‐induced dissociation spectra of all resolved isomers are discussed. Copyright © 2016 John Wiley & Sons, Ltd.     

Spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile

Spiro 2-pyrrolidin-5-ones were obtained from N-substituted succinimides by a two-step procedure, involving 5- or 6-endo-trig cyclisation of N-acyliminium ion intermediates with a tethered aromatic π-nucleophile.     

Addition of carbon nucleophiles to cyclic N-acyliminium and oxocarbenium ions under solvent-free conditions

The InCl₃-catalyzed addition of carbon nucleophiles to cyclic N-acyliminium and oxocarbenium ions under solvent-free conditions at room temperature is described. The corresponding α-substituted heterocycles were obtained in moderate to excellent yields.     

Stereoselective synthesis of trans-2,3-disubstituted pyrrolidines via addition to N-acyliminium ions

An efficient and stereoselective synthesis of trans-2,3-disubstituted pyrrolidines is described. The intermolecular alkylation of racemic N-acyliminium ions generated in situ from the corresponding 3-substituted lactams proceeds stereoselectively and in high yield.     

Novel Approach to Isoindolo[2,1-a]quinolines

An N-acyliminium ion approach towards the synthesis of isoindolo [2,1-a]quinolines by an intramolecular process is described.     

Zum Mechanismus massenspektrometrischer Fragmentierungsreaktionen: XI—Einfluß von Substituenten auf die Bildung cyclischer Fragment-Ionen in den Massenspektren von N,N-Dimethyl-N′-2-chlorphenylformatmidinen und 2-Chlorformaniliden

Molecular ions of N,N-dimethyl-N′-2-chlorophenylformamidines (III) and 2-chloroformanilides (IV) lose a chlorine atom to give benzimidazolium and benzoxazolium ions, respectively. As with N,N-dimethyl-N′-phenylformamidines (I), a linear relationship exists between the Hammett σ-constants and the effect of substituents on the ionisation potentials of substituted III and IV. In contrast to this, the appearance potentials of the cyclic fragment ions of III and IV cannot be easily related to polar effects of substituents; these effects are similar for the cyclic fragment ions of I, III and IV however. Furthermore, the intensities of these ions are influenced in the same direction by substituents in the mass spectra of I, III and IV, and are strongly reduced by electron donating substituents in the para position. The formation of cyclic fragment ions in the mass spectra of I, III and IV therefore occurs by the same mechanism.     

Diastereoselective borono-Mannich reactions on cyclic N-acyliminium ions

The addition of boronic acids to five- and six-membered ring N-acyliminium ions has been employed to prepare 5- and 6-substituted 4-hydroxypyrrolidin-2-ones and 5-hydroxypiperidin-2-ones, respectively, in a diastereoselective fashion.     

Spectral and thermal studies on new hydrazinium metal sulfite dihydrates

Some new hydrazinium transition metal sulfite dihydrate complexes of the formula (N₂H₅)₂M(SO₃)₂(H₂O)₂ where M=Fe, Co, Ni, Cu and Zn have been prepared and characterized by hydrazine and metal analyses, magnetic studies, electronic and infrared spectra and thermal analysis. The magnetic studies coupled with electronic spectra of iron, cobalt, nickel and copper complexes indicate their high spin octahedral nature. However the zinc complex is diamagnetic and show only the charge transfer transition. The infrared spectra shows that both the hydrazinium ions are coordinated to the metal ions, the sulfite ions are present as bidentate ligand. The simultaneous TG-DTA of these complexes were investigated in air and nitrogen atmospheres. In air, cobalt, nickel and zinc complexes give respective metal sulfate as the final residue while iron and copper complexes give the mixture of respective metal oxide and sulfate as the decomposition product. In nitrogen atmosphere respective metal sulfites are formed as the end residue.     

Synthesis of substituted pyrrolidines and piperidines from endocyclic enamine derivatives. Synthesis of (±)-laburnamine

Functionalization of the α- and β-positions of readily available endocyclic enamine derivatives provides a convenient method for the formation of substituted pyrrolidines and piperidines. α-Alkoxy-β-iodopyrrolidines are formed by the electrophilic addition of iodine to the endocyclic enamine double bond of an N-substituted 2-pyrroline, and nucleophillic attack by an alcohol on the intermediate iodonium ion. The resultant α-alkoxy-β-iodopyrrolidines can be used in radical cyclization reactions to give bicyclic hemiaminal compounds, which can be further elaborated using N-acyliminium chemistry to form α,β-cis-dialkylsubstituted pyrrolidines. A strategy for the incorporation of amino functionality at the β-position was also established by using iodoamination of the enamine double bond, followed by migration of the amine functionality through an aziridination/methanolysis protocol. An alternative method uses an azidomethoxylation protocol using ceric ammonium nitrate (CAN) in the presence of NaN₃ and methanol. Formation and trapping of the N-acyliminium ions derived from these substrates, afforded the 3-carbamate and 3-azido-2-substituted products with good diastereoselectivity, with the preferential formation of the trans and cis stereoisomers, respectively. Using the sequential iodoamination, aziridination in methanol and N-acyliminium transformation, trans-3-NHCO₂Me-2-allyl-pyrrolidine was prepared, which was used as the key precursor in a synthesis of the natural 1-amidopyrrolizidine alkaloid, (±)-laburnamine.     

A practical method for the synthesis of pyrrolizidine, indolizidine and pyrroloazepinolizidine nucleus

The alkylation of α,ω-dibromoalkanes, with the sodium salt of succinimide, followed by the reduction with sodium borohydride gives the respective N-ω-bromoalkyl-5-hydroxy-2-pyrrolidinones. These substrates are precursors of N-acyliminium ions under acidic conditions. The condensation of these intermediates with ethyl malonate in the presence of TiCl₄ and diisopropylethylamine following the intramolecular cyclization provides a convenient route to substituted pyrrolizidinone, indolizidinone and pyrroloazepinolizidinone nucleus in a good yield.     

Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

In the presence of catalytic amount of bismuth bromide (5 mol %) the α-amido p-tolylsulfones are converted into N-acyliminium ions, which undergo the nucleophilic addition of trimethylsilyl cyanide (TMSCN) to provide the N-protected α-amino nitriles in very good yield. A variety of α-amido p-tolylsulfones were prepared from aromatic as well as aliphatic aldehydes for the synthesis of α-amino nitriles.