Iminium ions highly electrophilic

You will again meet the highly electrophilic iminium ions produced by reaction of formaldehyde with amines in Chapter 27, where we introduce you to the Mannich reaction. 

In the presence of an enolizable aldehyde or a ketone, the resultant electrophilic iminium ion reacts in situ with the enol to produce, after neutralization, the corresponding (3-amino ketone, also called a Mannich base. Unsymmetrically substituted ketones are aminomethylated preferentially at the more highly substituted carbon of the enol. 

As mentioned previously, acyliminium ions are electrophilic enough to react intramolecularly even with nonactivated alkenic ir-systems. These cyclization reactions have been recognized and elaborated as valuable tools in the stereoselective total synthesis of quinolizidine, indolizidine and pyrrolizidine alkaloids. A typical example from Speckamp s laboratory is the highly stereospecific acid-catalyzed cyclization of (81) to (83 Scheme 40), presumably via the corresponding acyliminium ion (82). Analogously, other more complex natural products, such as the antiulcerogenically active alkaloid ma-trine (85), can be built up with high stereocontrol (Scheme 41), with an enol ether function as a more electron-rich nucleophile for the intermediate iminium ion (84). ... 

Under neutral conditions and at low temperature indole reacts with a mixture of formaldehyde and dimethylamine by substitution at the indole nitrogen it seems likely that this reaction involves a low equilibrium concentration of the indolyl anion. In neutral solution at higher temperature or in acetic acid, conversion into the thermodynamically more stable, 3-substituted product, gramine, takes place. Gramine is formed directly, smoothly and in high yield, by reaction in acetic acid. The Mannich reaction is very useful in synthesis because not only can the electrophilic iminium ion be varied widely, but the product gramines are themselves intermediates for further manipulation (section 17.12). 

Reaction of phenylethyl amine with aldehyde or ketone forms intermediate imine, which under the acidic conditions is protonated to give the highly reactive iminium ion. Electrophilic substitution on the aromatic ring provides 1,2,3,4-tetrahydro isoquinoline after rapid loss of a proton and... 

The role of the imidazolidinone catalyst 100 employed is depicted in Scheme 6.13. In the proposed cycle, the nucleophile (Nu) is added over the first formed a,p-unsaturated iminium ion 102. After a fast hydrolysis, adduct 104 and catalyst 100 are released. The adduct 104 would then enter in the second catalytic cycle to form the active enamine 105, which could trap the electrophile (E) present in the reaction in a highly diastereoselective addition. 

However, when an imine is protonated, the resulting iminium ion is highly electrophilic ... 

Two highly efficient and very practical alternatives have emerged in recent years (Scheme 1.2). One of these approaches consists of activating the acceptors by reversible conversion into a chiral iminium ion. Thus, the reversible condensation of an a,p-unsaturated carbonyl compound with a chiral secondary amine provides a chiral a,p-unsaturated iminium ion. A face-selective reaction with the nucleophile provides an enamine, which can be either reacted with an electrophile and then hydrolysed, or just hydrolysed to a p-chiral carbonyl compound. The second approach is the enamine pathway. If the nucleophile is... 

Diamination was first reported in 2007 by Jprgensen and coworkers with a combination of enamine and iminium-ion activation modes catalyzed by the diaryl prolinol silyl ether 3 (10 mol%) [18]. The sequential addition of succinimide as the nucleophile and diethyl azodicarboxylate as the electrophile afforded the syn-diaminated products 32 and 33 in promising overall yield (40%) with high levels of stereoselectivities (dr up to 8/2, ee 99%) (Scheme 12.14). 

---