Cations iminium

Enamines of A" -3-ketones (45) are stable to lithium aluminum hydride, but lithium borohydride reduces the 3,4-double bond of the enamine system." In the presence of acetic acid the enamine (45) is reduced by sodium borohydride to the A -3-amine (47) via the iminium cation (46). ... 

In 1954 Stork et al. (i) reported that the alkylation of the pyrrolidine enamine of cyclohexanone (5) with methyl iodide followed by acid hydro-I ysis led to the monoalkylated ketone. It was thus obvious that the enamine (7) derived by the loss of proton from the intermediate methylated iminium cation (6) failed to undergo any further alkylation. 

For purposes of characterization of enamines the perchlorate salts are preferred, as they crystallize well, and the perchlorate anion has no tendency to add to the iminium cation. Other salts, including hexachlorostannates (13), hexachloroantimonates (13), chlorides, bromides, tetraphenylborates, and nitrates, have also been used. Recently a method for the preparation of iminium salts directly from aldehydes or ketones and the amine perchlorate has been reported (16). 

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. 

Trichloroacetic acid behaves somewhat similarly in that protonation of the enamine occurs l7J7d). Subsequent decarboxylation of the trichloro-acetate gives trichloromethyl anion, which adds to the iminium cation to give the trichloromethyl amine derivative. Thus the enamine (113) undergoes reaction with trichloroacetic acid to give N-[l-(trichloromethyl)cyclo-hexyl]-morpholine (8). The latter compound undergoes rearrangement on... 

The mechanism was then reexamined 25 years later in 1997 by Kappe. Kappe used H and C spectroscopy to support the argument that the key intermediate in the Biginelli reaction was iminium species 16. In the event, 5 reacted with 3a to form an intermediate hemiaminal 17 which subsequently dehydrated to deliver 16. Iminium cation 16 then reacted with 6 to give 14, which underwent facile cyclodehydration to give 15. Kappe also noted that in the absence of 6, bisureide 8 was afforded as a consequence of nueleophilic attack of 16 by urea (3a). This discovery confirmed the conclusion of Folkers and Johnson in 1933. As far as the proposal from 25 years earlier by Sweet and Fissekis, Kappe saw no evidenee by H and NMR spectroscopy that a carbenium ion was a required species in the Biginelli reaetion. When benzaldehyde (5) and ethyl... 

Keywords imine, iminium cations, nitriles, nitroso compounds, azo compounds, azadienes, nitroso alkenes... 

Eq. 25) [295]. A similar mechanism has also been proposed for the electrolysis of isobutyric and pivalib acid in acetonitrile [296]. As the intermediate alkyl cation can rearrange and the intermediate iminium cation can furthermore react with the starting carboxylic acid three different amides can be isolated (Eq. 26) [295 a]. The portion of the diacylamide can be considerably increased if the electrolyte consists of acetonitrile/ acetic acid [295 b]. 

Another approach to the generation of an iminium cation suitable for cyclization is the protonation of dihydropyridine derivatives. One example can be found in Scheme 48, where treatment of compound 243 with acid induced its cyclization to indoloquinolizine 244, a precursor in the first total synthesis of (i)-tangutorine 245, an alkaloid isolated from a traditional Chinese medicinal plant <2001TL6593>. 

Intramolecular cyclizations could also be achieved by oxidation of 57 with PCC to 65 regioselective addition of an organometallic onto the 7(2)-carbonyl carbon of 65 was followed by treatment with acid to generate the iminium cation, and intramolecular trapping of the cation by an appropriate N-2 substituent (e.g., phenylethyl substituent) <2001TA2883> or C-4 substituent (e.g., benzyl group) <2002T6163>. 

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>. 

In solution, l-(ot-aminoalkyl)benzotriazoles 562 are in equilibrium with iminium cation 563 and hence with their benzotriazole-2-yl isomers 564 (Scheme 89). Protonation or complexation of the benzotriazolyl moiety (e.g., Mg, Zn, B, A1 reagents) facilitates the transformation. Intermediate iminium cations 563 can be trapped by nucleophiles providing synthetic pathways to various amines. Many such reactions are described in CHEC-II(1996) <1996CHEC-11(4)1 >, and some newer results are compiled in reviews <2005T2555>. 

Ring-chain Tautomerism of Nitronates and Derived Iminium Cations... 

The attack of a cation on the oxygen atom of SENA should give rise to iminium cations, which can be stabilized by deprotonation or desilylation. (These possibilities will be considered in detail in Section 3.5.)... 

Actually, the reactions of AN with bases produce reversibly carbanions A, which are the major intermediates in the classical reactions of AN (Henry, Michael, and Mannich reactions). The reactions of AN with acids afford iminium cations B (also reversibly), which are the key intermediates in the Nef reaction... 

Chart 3.22 New approach to the generation of iminium cations from AN. 

For this purpose, the reactions of various types of nitronates (348) with trialkylsi-lyl triflates in CD2CI2 were studied by low-temperature NMR spectroscopy. More than 10 iminium cationic intermediates (349) were detected (Scheme 3.204) (478). 

These data show that the iminium cations exist in dichloromethane as ion pairs. Apparently, this is the reason why the ring inversion in cation (349a) is hindered, taking into account that the ring inversion requires the energy-consuming cleavage of the ion pair. 

As can be seen from Table 3.23, the electrophilicities E, which were determined according to Mayr s scheme (482), vary in a wide range and depend mostly on the substituents at the C-3 atom (see the last entry in Table 3.23). On the whole, the electrophilicities E for bis-oxyiminium cations are in the same range as those for classical iminium cations (482) (e.g., see Ref. 483 for [C=NMe2]+, E = —6.69). 

Table 3.22 The C,C-coupling of iminium cations 349 with reference nucleophiles...

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. 

Intramolecular C,C-Coupling Reactions of Bis-N,N-(trimethylsiloxy) Iminium Cations Here we consider one of the mechanistic schemes of intramolecular C,C-coupling reactions of bis-/V,/V-(siloxy)iminium cations generated by silylation of P-nitroalkylated derivatives of malonic ester (382) (Scheme 3.216). 

Selected Features of the Chemistry of N,N-Bis-Trimethylsiloxy-Substi-tuted Cyclopropanes and Dihydrofurans Scheme 3.217 shows selected features of the chemistry of compounds prepared by intramolecular trapping of bis-N,N-(trimethylsiloxy)iminium cations. 

These enoximes can be prepared through available annelated six-membered cyclic nitronates (391) by their silylation giving rise to the iminium cations A, whose deprotonation affords annelated 2H-5,6-dihydrooxazines (392). After the known retro-fragmentation (490), the latter compounds are transformed into the target conjugated en oximes (395). 

But BENAs could be active in reactions with electrophiles due to stabilization of the resulting carbo-iminium cations (Scheme 3.230, see also Section 3.5.2.6)... 

Norton and coworkers found that catalytic enantioselective hydrogenation of the C=N bond of iminium cations can be accomplished using a series of Ru complexes with chiral diphosphine ligands such as Chiraphos and Norphos [68], Even tetra-alkyl-substituted iminium cations can be hydrogenated by this method. These reactions were carried out with 2 mol.% Ru catalyst and 3.4—3.8 bar H2 at room temperature in CH2C12 solvent (Eq. (39)). 

After some mechanistic studies showing that the reduction of N,0-acetals proceeds via a prochiral iminium cation, Bomer et al. aimed at finding an enantioselective catalyst for this transformation by preparing a library of 144 catalysts... 

Overman et al. <1996JA9062> and Kibayashi et al. <2002JOC5517> have utilized the same alkynyl intermediate 222 as a substrate in their chemistry (Scheme 47). While the first group uses a nucleophilic attack of the triple bond on the iminium cation 223, the second group performs a regioselective hydrostannylation, followed by Pd-catalyzed carbonylation, to provide the precursor 224 to the cyclization step. 

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-... 

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