Nitrogen Stabilized Carbocations

A Mannich/Michael reaction sequence was used by Waldman for the formation of several piperidone derivatives. The reaction of 285 with 286 in the presence of a 

Using diene 288 and imine 289, the tandem Mannich/Michael reaction sequence afforded the vinylogous amide 290 in 66% yield (97TL2829). Imines derived from other aldehydes were also studied, providing derivatives of 290 in moderate yields 

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Step 4 The oxygen protonated carbmolamme loses water to give a nitrogen stabilized carbocation CeHs H... 

Step 5 The nitrogen stabilized carbocation is the conjugate acid of the imine Proton transfer to water gives the imine... 

For reactions of A-acyliminium ions with alkenes and alkynes one has to distinguish between A-acyliminium ions locked in an s-trans conformation and those which (can) adopt an s-cis conformation. The former type reacts as a (nitrogen stabilized) carbocation with a C —C multiple bond. Although there are some exceptions, the intramolecular reaction of this type is regarded as an anti addition to the 7t-nucleophile, with (nearly) synchronous bond formation, the conformation of the transition state determining the product configuration. 

Water Nitrogen-stabilized carbocation Hydronium ion IV-Benzylidenemethylamine... 

This section deals with addition reactions to cyclic N-acyliminium ions of type (69), locked in the s-trans conformation. Being unable to participate as a 47r-system in a Diels-Alder type reaction, (69) simply reacts as a nitrogen-stabilized carbocation with carbon-carbon multiple bonds. The products can be either the result of addition (70) or substitution (71 and 72), mainly dependent on the substitution pattern of the nucleophilic multiple bond (equation 37). 

Tertiary electrophiles alkylate bydroxylamines through the SatI mechanism. These reactions (e.g. equation 10) are practically feasible only for compounds forming highly stabilized carbocations such as trityl , or 2-(p-alkoxyphenyl)propyl. All these reactions proceed exclusively on the nitrogen atom and have been used for A-protection of the amino groups in bydroxylamines. 

When a stabilized carbocation cannot form, the geometry of the double bond can direct the regiochemistry. Due to steric interactions during the attack of the nucleophilic nitrogen, starting from (Z)- or ( )-allylic imidates, 4,5-dihydrooxazoles 2 or 5,6-dihydro-4//-l,3-oxa-zines 3 were respectively obtained by halocyclization (Table 8, entries 6-11)145- 148. 

Line structure can be deceptive in eliminations because the important C-H bond is not explicitly drawn out, in this example, when there is a lone pair stabilized carbocation intermediate in the El. The loss of a formal charge may be difficult to notice in reactions that drop off a proton because the proton is commonly not drawn as one of the products. Since the proton lost was not drawn in the line structure on the left, it was simply forgotten. The arrow made a double bond in the right place but flowed the electrons the wrong way away from the positive center and not toward it. Besides the loss of the formal charge, the lone pair on nitrogen was lost it was assumed in the product, but the incorrect arrow did not form it. The right side shows the correct electron flow path Dg, deprotonation of a carbocation to form a pi bond. 

Using curved arrows, write a mechanism to show how each of the glycosyl donors produces the oxygen-stabilized carbocation. For part (a) consult Section 16.17 on sulfides and 8.12 on triflates for part (b) examine step 2 in Mechanism 19.8, and assume that silylation occurs at nitrogen in the glycosyl imidate ester. 

Another structural feature that increases carbocation stability is the presence, adjacent to the cationic center, of a heteroatom bearing an unshared pair," for example, oxygen," nitrogen," or halogen. Such ions are stabilized by resonance ... 

Pyrrolidine itself is not sufficiently activated to allow direct C—C bond formation at positions 2 or 3. However, under certain conditions the nitrogen atom may stabilize a reactive carbanion or carbocation (iminium ion). Both approaches have been fruitful. 

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