Iminium cations, formation

The reaction has been applied to more complex enamines 13) and to dienamines 19). The reduction may be rationalized by initial protonation at the enamine carbon and subsequent decarboxylation of formate ion and addition of the hydride ion to the iminium cation. This mechanism has been given support by the reaction of the enamine (205) with deuterated formic acid 143) to give the corresponding amines. The formation of 206 on reaction with DCOOH clearly indicates that protonation at the enamine carbon is the initial step. 

Treatment of the protected aldehyde 342 with a TFA/water/chloroform mixture results in the formation of a 10-membered intermediate iminium cation intramolecular attack of this electrophile at C-2 of the indole (an intramolecular Pictet-Spengler reaction) gives the isolated tetracyclic product 343 in good yield (Equation 124) <1995T4841>. 

If the substituent R4 is not conjugated with the carbonyl group (compounds (377) in Scheme 3.215), silylation proceeds in a different fashion (153, 292, 470). After the formation of the initial SENAs (378), the latter undergo reversible cyclization to give cyclic iminium cations B, which are stabilized by deprotonation of the C-4 atom to form the cyclic intermediates 2// -5,6-dihydrooxazines C. 

The minor metabolite 11.167 in Fig. 11.20 can be viewed as a cyclic Schiff base formed by reaction of the NH2 and C=0 groups. In contrast, the major and unexpected metabolite 11.166 is also a Schiff base, but, more precisely, it is a permanent iminium cation formed between a secondary amino and a keto group. Presumably, formation of 11.166 is facilitated sterically by the spatial proximity of the two reacting groups. Another factor might well be the stability of the iminium cation, which is expected to be high in acidic media (proton repulsion by the positive charge) and in alkaline media (ab-... 

This behaviour results from initial formation of an intermediate with two potential leaving groups, an amide anion R2N and the aluminate anion (OAlHs). Aluminate is the better leaving group, and its loss produces an iminium cation that is also subject to further reduction. This gives us the amine product. 

The Mannich reaction is best discussed via an example. A mixture of dimethylamine, formaldehyde and acetone under mild acidic conditions gives N,N-dimethyl-4-aminobutan-2-one. This is a two-stage process, beginning with the formation of an iminium cation from the amine and the more reactive of the two carbonyl compounds, in this case the aldehyde. This iminium cation then acts as the electrophile for addition of the nucleophile acetone. Now it would be nice if we could use the enolate anion as the nucleophile, as in the other reactions we have looked at, but under the mild acidic conditions we cannot have an anion, and the nucleophile must be portrayed as the enol tautomer of acetone. The addition is then unspectacular, and, after loss of a proton from the carbonyl, we are left with the product. 

We thus have standard imine formation in this case, the secondary amine leads to an iminium cation. This is attacked by the ketone nncleophile. This cannot be an enolate anion because of the mild acidic conditions under which the reaction proceeds, so we formnlate it as involving the enol tantomer. Accordingly, we need to include an acid-catalysed enolization step. 

The mechanism of imine formation is standard, as seen in the other examples. The cyclization reaction is then like the Mannich reaction, attack of an enol on to the iminium cation. This time though, the nucleophile is provided by the resonance effect from the phenol system. 

A-Dialkylaminomethylbenzotriazoles usually exist in the crystalline state solely as the N(l) isomers, but in solution they form equilibrium mixtures of the N(l) (209, 210) and N(2) (211) isomers <75JCS(Pl)l 181, 87JCS(Pi)2673). The N(l) and N(2) isomers are of nearly equal stability in nonpolar solvents and in the gas phase (2 1 ratio on statistical grounds). Polar solvents favor the 1- and 3-substituted forms over the 2-substituted, and conversely substituents at positions four and seven favor the 2-substituted form. The interconversion of these N(l) and N(2) isomers proceeds intermolecularly, as demonstrated by cross-over experiments, by a dissociation-recombination mechanism involving the formation of intermediate iminium cations and the benzotriazole anion. 

On standing, LXXIXb undergoes a rearrangement, apparently with the formation of an iminium cation (LXXX)—a reaction analogous to the formation of an ethyleneiminium cation from V-alkyl-V,./V -bis(2-chloroethyl)-amine.184 The di-O-mesyl ester (LXXXI) of LXXVIII is remarkably resistant to catalytic de-O-acetylation. 

Activation of enones by formation of an iminium cation is an interesting strategy that has been highlighted for organocatalysis in recent publications. A similar concept has been investigated for the enantioselective Michael reaction of malo-... 

Enamines are classical bidentate reagents that interact with electrophilic species via both their nitrogen and their / carbon atoms. The simplest instance of such reaction (equation 2) is a proton attack which results in the formation of an iminium cation (5) and an... 

The resulting achiral iminium cations, with chiral phosphate counteranion, were then enantioselectively reduced using an achiral Hantzsch ester (dihydropyridine) providing enantioenriched amines. During this imine reduction study, one example was shown in which acetophenone and p anisidine [16] were prestirred in the presence of toluene and 4 A molecular sieves [17] for 9h (imine formation), after which the temperature was raised to 35 °C, and the Hantzsch ester (1.4 equiv) and phosphoric acid (TRIP, 5 mol%) were added to give the amine product in 88% ee over an additional 45 h. This is an exciting observation and while not a reductive amination, it is an operational improvement over simple imine reduction which requires imine isolation. 

The formaldiminium ion formed from the reaction of 4-hexynylamine (90 R = R = Me) with paraformaldehyde and camphorsulfonic acid is reported not to cyclize when heated for 1 h at 1(X) C in the weakly nucleophilic solvent acetonitrile. However, when nucleophilic salts are added the 3-alkylidene-piperidines (91) are formed in good yields (Scheme 32). Attempted cyclizations of (90) in the presence of weaker nucleophiles such as benzenethiol or methanol were less effective, the former yielding <15% of the expected alkylidenepiperidine product, while the latter provided no products of cyclization. If the strong nucleophile iodide is employed, even a weakly nucleophilic terminal alkyne can be successfully cyclized. In all of these cyclizations of 4-alkynylamines only formation of a six-membered ring product was observed. The (2)-stereochemistry of the alkylidene side chain evolves from antarafacial addition of the internal iminium cation and the external nucleophile to the alkyne. 

Santamaria et al [42] for synthesizing a-amino nitriles in the alkaloid field and also for preparing 6-cyano-l,2,3,6-tetrahydropyridine from corresponding pyridine nucleus. A similar approach has also been used by Sundberg et al. [43a,43b] for the cyanation of Catharanthine alkaloids. In situ trapping of the iminium cation (37) by allyltrimethylsilanes or silyl enol ethers is also shown [44] recently as a direct —C-C— bond formation methodology at the a-posi-tion of tertiary amines (Scheme 8). The success of this reaction is based on the comparative correlation of ion-pair yield with the AGg, values from amines and enol ethers. 

Starting from 1,3,5-trithiane, three novel mono- to trifulvathianes 163-165 have been prepared by (1) formation of the 1,3,5-trithiane anion and (2) reaction with either 4,5-dimethyl-l,3-dithia-2-iminium cation 166a or the 4,5-dimethyl-l,3-dithia-2-methylthiolium cation 166b (Figure 9). Spontaneous loss of amine or mercaptan provides... 

Crucial to the course of the hydrogenation reaction is the formation of the iminium cation, which competes with the formation of ammonium salts. The hydrogenation of aniline derivatives could be readily accomplished, which copes most probably with the fact that aryl-substituted imines are more basic than aryl-substituted amines. The iminium cations are therefore always accessible in kinetically relevant... 

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