From nitrilium ions

The tetrachloroferrate or tetralluoroborate salts of alkylated alkyl- or aryl-nitriles (nitrilium ions) are reduced to imines with triethylsilane. Subsequent hydrolysis of the intermediate imines leads to aldehydes in good yields, thus providing an excellent overall route to aldehydes from nitriles (Eq. 338).28,562... 

With one exception, naphthalen-l,4-imines with a double bond between C-2 and C-3 are not known to dissociate thermally by either possible retro-Diels-Alder pathway (the reverse of reactions described in Section III, A, 1 and 2), and the enthalpy requirements for the formation of a benzyne or an acylic acetylene are doubtless unfavorable. However, the mass spectra of compounds 93-99 reveal one important fragmentation of the molecular ions to be loss of dimethyl acetylene-dicarboxylate, and another fragmentation pathway involves the formation of nitrilium ions MeC=NR and PhC=NR from 93-95 and 96-99, respectively. ... 

In the Beckmann reaction alternative ionic intermediates, two nitrilium ions (225, via route a or b and 237, via route c) or one iminium ion (235, via route b or c), may be formed from the activated oximes (Scheme 7). 

The formation of a very electrophilic intermediate 258 from 256 and 257 is proposed (equation 78). The hydroxyl group of the oxime adds to 259, giving a reactive cationic species 260 that rearranges and affords the nitrile 261 (in the case of aldoxime, equation 79), or the amide 262 upon hydrolytic workup (equation 80). The conversion of 260 to the nitrilium ion should occur through a concerted [1,2]-intramolecular shift. This procedure can be applied in the conversion of aldoximes to nitriles. It was observed that the stereochemistry of the ketoximes has little effect on the reaction, this fact being explained by the E-Z isomerization of the oxime isomers under the reaction conditions. 

Pyridyne (98) is the most stable of the three isomers, and, in contrast to 100 and 102, has a higher preference for the singlet ground state than 13. This change suggests the participation of nitrilium ion structure 98B and possibly 98C in the resonance hybrid, which is also evident from the shortening of the N—C2 bond compared to the N—C6 bond. 

On the other hand, it has been demonstrated that the a-D-glucopyranosyl aceto-nitrilium ions are stereospecifically generated from the corresponding oxocarbenium ions in dry acetonitrile [43-45]. These results indicate that the acetonjtrilium ions are axially oriented by an anomeric effect. Recently, it has been concluded from the conformational analyses of glucopyranosyl-ammonium and glucopyranosyl-imidazolium derivatives that the reverse anomeric effect does not exist [46,47]. 

Therefore, it seems most plausible that the stereospecific generation of the p-aceto-nitrilium ion (d) of Neu5Ac from the oxocarbenium ion (c) holds the key of the re-preponderant formation of sialyl glycosides in acetonitrile. Thus, the reactive nucleophiles, such as OH-6 of 17 have a chance to attack on other intermediates (a) (c) before the complete... 

A simple two-step synthesis of 4-arylthieno[3,2-c]pyridine-6-carboxylic acids has recently been presented by Eweiss (Scheme 74) (B-81MI31703). The condensation of thiophene-2-carbaldehyde with an N -aroylated a-amino acid yields a thienylidene azlactone (281) which on treatment with AICI3 is converted to a thieno[3,2-c]pyridine (283). A nitrilium ion (282) resulting from a vinyl-oxygen fission is probably involved as an intermediate. Sandberg s method already mentioned in the previous section has also been applied to the synthesis of thieno[3,2-c]pyridines (Scheme 75). 

More recently, Hegarty has investigated the reactivity of nitrilium ion 30 and found that in the product formed under kinetically controlled conditions, the nitrogen electron pair is always trans to the incoming nucleophile, i.e. 31. In an excellent review (10), Hegarty states that in spite of careful searching, they have unable to observe any detectable quantity of the cis product 32 (or of a product which would be derived from 32 by further chemical transformation). 

The earliest reports of constrained Ugi adducts derived from bi-functional precursors appeared in the 1960s with the preparation of penicillin derivatives such as 68, involving sequential Asinger and Ugi four-component reactions (Scheme 11.13). As such, the synthesis represents the shortest preparation of a known penicillin derivative [65], The /Mactam ring is formed after isocyanide addition to the cyclic Schiff base, followed by carboxylate nitrilium ion trapping and acyl transfer to give the final penicillin core. In this example, the amine and carboxylic acid inputs may be considered tethered. 

It is assumed137 that the reaction proceeds by path a so long as the carboxonium ions 284 are sufficiently reactive for reaction with weak nucleophilic nitriles (e.g. as is the case when the ions 284 are acyloxycarbocations 225, E = acyl). Otherwise (284, E = H, Aik), path b is followed because in this case the highly reactive nitrilium ions 287 can be generated from weak nucleophilic nitriles. Both paths lead to the same A-acyliminium intermediate 28949 (equation 77). 

In a similar context Amdtsen developed a new pyrrole synthesis from alkynes, acid chlorides either imines or isoquinolines, based on the reactivity of isocyanides (Scheme 35a) [197]. Although all atoms from the isocyanide are excluded from the final structure, its role in the reaction mechanism is crucial. The process takes place through the activation of the imine (isoquinoline) by the acid chloride to generate the reactive M-acyliminium salt, which is then attacked by the isocyanide to furnish a nitrilium ion. This cationic intermediate coordinates with the neighboring carbonyl group to form a miinchnone derivative, which undergoes a [3+2] cycloaddition followed by subsequent cycloelimination of the isocyanate unit, to afford the pentasubstituted pyrrole adducts 243 and 244 (Scheme 35a, b). 

Although isolated in small amounts, the pyridinium salts 282 (arising from the iodine-mediated oxidation of DHPs 281) do not afford benzimidazolium salts 279 in the presence of isocyanides. A likely pathway may start with the iodo-dihy-dropyridinium intermediate 280, which can be formed by interaction of iodine with the reactive double bond of the DHPs (Scheme 44). The isocyanide may subsequently attack these species to generate the nitrilium ion T, which interacts with a second equivalent of isocyanide to form cation U. This intermediate undergoes an intramolecular trapping by the enamine unit to close the bicyclic system V... 

A number of nitriles added to bicyclic alkenes after conversion into a nitrilium ion intermediate, generated by treatment with sulfuric acid. Thus, derivatives of 3-azatricyclo[5.3.1.04,9]undecene 30 were obtained starting from 2,6-dimethylenebicyclo[3.3.1]nonane 29 with total diastereose-lectivity187. 

If the rearrangement of oxime sulfonates is induced by organoaluminum reagents,the nitrilium ion intermediate 82 is captured by the nucleophile originally attached to the Al. By this means an oxime can be converted to an imine, an imino thioether (R-N=C-SR), or an imino nitrile (R-N=C-CN). " In the last case, the nucleophile comes from added trimethylsilyl cyanide. The imine-producing reaction can also be accomplished with a Grignard reagent in benzene or toluene. " ... 

---