Trapped intermediate iminium ions

The mechanism for 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)-mediated oxidative C—C bond formation has been supported by characterization of a trapped intermediate iminium ion (using X-ray crystallography, elemental analysis, and solid-state NMR spectroscopy), which has been shown to react with a range of nucleophiles including a malonate ion ... 

Perhydrooxazolo[3,2- ]pyridines 338 are excellent precursors of iminium ions 339 obtained after treatment of the oxazolidine with either a Bronsted or Lewis acid. Trapping of these intermediate iminium ions with nucleophiles then allows for substitution at the C-8a position together with ring opening, yielding functionalized piperidines 340 (Scheme 93). 

Argoti, D. et al. (2005) Cyanide trapping of iminium ion reactive intermediates followed by detection and structure... 

The Ru(II)/ROOH system can also be used to oxidize tertiary amines. The intermediate iminium ion is formed, as described earlier for secondary amines, and can be trapped by nucleophiles. Thus, the ruthenium-catalysed oxidation of tertiary amines with hydrogen peroxide in methanol can be performed to give the corresponding a-methoxyamines with high efficiency as illustrated in Fig. 24 [ 137]. Another example is the selective demethylation of tertiary amines in methanol with a combination of Ru(II) and H202, followed by hydrolysis of the intermediate a-methoxylated amines. For example, the methoxylation of N,N-dimethyl-p-toluidine followed by treatment with 2 N HC1 solution gave N-methyl-p-toluidine in 75% yield (Eq. 35) [137]. 

Reductive cleavage of imidazolidines 641 was implicated in the one-pot synthesis of N,N,N -trisubstituted ethylenediamines 643 from V,V -disubstituted ethylene diamines and an aldehyde R CHO. Presumably the intermediate iminium ion 642 is reduced by NaBH4 (Scheme 154) <2003SC3193>. Naphthalene-catalyzed lithiation of l,3-dimethyl-2-phenylimidazoline 644 leads to benzylic C-N bond cleavage. The intermediate dianion can be trapped with electrophiles (HjO, alkyl halides, ketones, and aldehydes) to afford diamines 645 <2005T3177>. 

The reported synthesis of the Amarylidaceae alkaloid ( )-epielwesine (50) also employed an iminium ion-vinylsilane in the key cyclization step (Scheme 23). Reaction of the (Z)-vinyltrimethylsilane (48) with TFA generated an intermediate iminium ion, which was trapped by the vinylsilane nucleophile to yield the cis fused heterocycle (49). 

Argoti D, Liang L, Conteh A, et al. Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chem Res Toxicol. 2005 18(10) 1537-1544. 

It seemed interesting to trap the iminium ion intermediate by performing an intramolecular aSH, so we plarmed a CHC/aSH/hydroformylation domino reaction (Scheme 10). This reaction involves an allylsilane present on the amine moiety which, in an acidic medium, reacts with an acyliminium ion derived from the CHC to form a vinyl group. The resulting vinyl double bond must be hydroformylated regioselectively by the rhodium complex present in the reaction medium to lead to a functionalized polycyclic structure. 

In some reactions regular ketones are used as pronucleophiles, raising the question of how, under the conditions of the reaction, the nucleophile is actually formed. In one CUI/O2 CDC reaction it was suggested that the beneficial effect of adding several equivalents of acetic acid to the reaction arose from the acid promoting enolization of the ketone and hence a faster trapping of the intermediate iminium ion. ... 

In the presence of alcohols, the corresponding ethers are formed and added nucleophiles such as chloride ion40 or azide ion41 lead to the chloro- and azido-amine products, respectively. Rate constants are independent of the concentration of added nucleophile. Labelled 180 from the solvent is incorporated in the product42. All the evidence points to a reaction mechanism where water is lost from the O-protonated reactant to give a nitrenium ion-iminium ion intermediate which is rapidly trapped by a nucleophile (H2O in this case) to give the final product. This is shown in Scheme 7. Protonation at N- is likely to be more extensive, but there is no pathway to products from the N-protonated intermediate. 

Although the anodic generation of a cation in a-position to nigrogen in aliphatic amines is not difficult, this type of reaction is not always useful to the synthesis of alkaloidal compounds, since the cation is not stable and a simple dealkylation is the usual follow-up reaction. N-monomethyl and N,N-dimethylanilines are, however, useful starting materials for the synthesis of the skeleton of tetrahydroquinoline. The anodic methoxylation of N,N-dimethylaniline 20 takes place at the methyl group, and an iminium ion intermediate 22 is easily generated by treatment of the methoxylat-ed product 21 with Lewis add. This intermediate can be trapped in situ with a variety of nucleophiles such as electron-rich olefins yielding tetrahydroquinolines 23 16). 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

As an extension, the same laboratory demonstrated the possibility of performing one-pot oxidative decarboxylations with concomitant iodina-tion when excess iodine was used (Scheme 16) [23]. As illustrated with the pipecolinic carbonate 26, this sequence can be performed followed by trapping of the iminium ion intermediate with 2-hexen-l-ol leading to the functionalized piperidine 27 in 71% yield. Subsequently, a 5-exo cyclization can be performed to give the bicyclic M,0-acetal 28, thus illustrating the potential of preparing complex systems in few steps. 

Trapping the carbonyl compound 1 in Scheme 3.3 with various nucleophiles provides various catalytic oxidative transformations of alcohols. When a primary or secondary amine is employed as a nucleophile, intermediate 13 undergoes nucleophilic reaction with amine to give iminium ion complex 14 along with water. Intramolecular hydride transfer of 14 gives the corresponding N-alkylated amine 15 with regen-... 

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