A-Acyliminium salts

The authors138 suggest that an initial stepwise (via intermediate 292) or concerted [2 + 2]cycloaddition of the nitrilium ion to the carbonyl group takes place forming intermediates 292 or 295 and 299, respectively. Ring-opening of the oxazetium cycle forms either 292 or 296 (as well as 300). The open-chain A-acyliminium salts 300 are... 

Moreover, it has been shownthat under conditions of electrophilic catalysis by acetyl cations the addition of ketones to nitriles proceeds more rapidly than the self-condensation of ketones shown in equations 34-36, Thus, cyclohexanone reacts with both benzonitrile and acetonitrile in the presence of perchloric acid/acetic anhydride mixture to form A -acyliminium salts 186 which are then converted to the JV-acylimines 187. The -acylaminoketones 97" did not form the salts 186 in a control experiment... 

It is well known that nitriles react with j8-chlorocarbonyl compounds in the presence of a Lewis acid to yield 4//-l,3-oxazinium salts, but now it has been shown that nitrilium salts combine with enones to give similar products. Thus enones and nitrilium hexachloroantimonates (150) combine to produce 4/f-l,3-oxazinium salts (152), but in some cases 6//-l,3-oxazinium salts (154) are formed instead and, while tautomerism between the 4H- and 6//-forms cannot be ruled out, oxetenium salts may participate in the reactions as common intermediates. One type of bond cleavage may give the carbocations (151) (especially when R = Ar), which cyclize to the 4//-tautomers and another may lead to A-acyliminium salts (153) (Scheme 41). The latter then ring close to 6//-l,3-oxazines. Evidence that such reactions do occur is provided, since A-acyliminium salts can be isolated in some cases <90S763>. 

Furthermore, a cycloreversion has been observed in the case of the thermally labile azoniaallene salts (61) (Z = O, S). When Z = S, this proceeds within an hour at room temperature to yield the aryl isothiocyanate and the charged cumulene (66) which is isolated as the acyliminium salt (67) <9ICB2537>. When Z = O and R = Ph, cycloreversion occurs at 83°C (refluxing 1,2-dichloroethane) to give the aryl isocyanate and (66), which is further cyclized to the quinazolinium salt (68) (Scheme 4) <89T5825>. 

When the A-ethylnitrilium salt 35 reacts with pinacolone 117, it gives the N-acyliminium intermediate 302 (equation 83) which can undergo a retropinacol rearrangement to yield the 2-oxazolinium salt 30386. 

As indicated by the experimental and theoretical results described above, both pathways a and b of reaction of carbonyl compounds with nitriles (equation 77) include two variants of the rearrangement of nitrilium salts having an oxygen function at a-position (285) and a-iminoalkyloxycarbenium ions 288. Both rearrangements lead to A-acyliminium cations 289 see equation 94. 

Jochims and coworkers48 138 139 cf equations 79, 80 and 84) as well as Lukyanov and colleagues49 cf equation 15) suggested that oxazetium salts like 344 and 346 are intermediates (or transition states) in these rearrangements. However, at the same time the opinion was advanced137 that the conversions of both nitrilium ions 285 and carboxonium ones 288 into A-acyliminium cations 289 are a second type of acid-catalyzed rearrangement of carbonyl compounds. 

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). 

A comprehensive kinetic study examining the reactivity of N-acylimines/N-acyliminium salts versus imines/iminium salts has not, to date, been published. Spectral data ( C NMR), however, would suggest... 

Other oxidative methods have been mendoned, such as the transformation of enamides (63) to a-hydroxylated acyliminium salts (70), via the hemiaminals (69). ... 

Compared with the simple iminium ions, the enhanced reactivity of acyliminium salts opens up a greatly enlarged spectrum of counter-nucleophiles, which now includes alkenes and aromatic compounds possessing no donor substituents (see Section 4.2.2.2.2). 

In addition analogous p-carboline syntheses with tryptamine and a,p-unsaturated aldehydes, hitherto impossible even under acid catalysis, were found to proceed very smoothly via acyliminium salts (78), induced by in situ acylation of the intermediate imine (77) with methyl chloroformate, allowing a first directed total synthesis of the indole alkaloid bonerine (79 Scheme 38). 

Instead of being cq>tured by external or internal heteroatom nucleophiles as in the preceding examples, the cationic intermediate resulting from the initial ring closure can eventually undergo a further cy-clization reaction with additional C-nucleophiles present in the same molecule. Such a tandem-type reaction cascade from (90) to (92), via the intermediate acyliminium salt (91), is presented in Scheme 43.9 ... 

The a-amidoalkylation reaction, which involves the addition of carbon nucleophiles (primarily aromatic rings, alkenes, cyanides, isocyanides, alkynes, organometallic and active methylene-containing compounds) to substituted amides (89) where X is a leaving group (Scheme 17), has been extensively re-viewed. A variety of organometallic condensations have since been reported which extend the scope of this reaction. The reactive intermediates in these reactions are considered to be N-acylimines (88) or N-acyliminium salts (SKI). Direct displacement of the a-haloalkylamide precursors (89 X = halogen) cannot in certain cases be discounted. 

During the total synthesis of the marine alkaloid (+)-lepadiformine by S.M. Weinreb et al., one of the key bicyclic N-acyliminium salt intermediates was subjected to a nucleophilic attack by an organocuprate. ° The resulting allyidimethylsilyl derivative was then treated under the Fieming-Tamao oxidation conditions to afford the corresponding hydroxymethyl compound in excellent yield. 

However, a considerable difference should be noted between a-hydroxyalkyl nitrilium ions 24 which contain an intramolecular nucleophilic center (OH group), and N-alkylnitrilium ions 26 which are the intermediates of a Ritter reaction. The transformation of ions 24 into the A -acyliminium ions 25 (equation 11) is evidently an intramolecular rearrangement (see Sections V.B and V.C), while the nitrilium salts 26 can be converted into ions 25 only by an oxidative dehydrogenation of amides 27 (equation 12). 

It should be emphasized that this method of synthesis of 5,6-dihydro-4/f-l,3-oxazines 40 gives heterocycles which are isomeric to that obtained by participation of N-acyliminium ions, i.e. the products 40 have inverted location of the heteroatoms relative to the three-carbon fragment of the cycle. Indeed, if the A -acyliminium ions participate in the formation of the heterocycle, the carbon atom (Cj) of starting aldehyde occupies position 4 of the heterocycle 45 (Figure 1) while Af -/erf-butylnitrilium salt 41 gives the heterocycles 46 with aldehyde fragment Cj at position 6, i.e. near the oxygen atom. 

The structures of the 2-oxazolinium, 1,3,5-oxadiazinium and 3-azapyrylium salts obtained by means of electrophilic catalysis by acylium ions ° point to the fact that their formation proceeds not via JV,7V-bis-acyliminium ions 332 and 333, but via the A -acyli mini urn ions 322 (i.e. those protonated at the nitrogen atom). In our opinion, the acetoxy azaallenium ions 335 can be transformed to the A -acyliminium cations 337 by a deacylation to the iV-acylimines 336, followed by protonation of the latter (equation 91). Such a process is quite possible under the conditions used for... 

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