Aza-Cope reaction

There is no unity of opinion in the literature concerning a classification, i.e, whether to call these transformations aza-Claisen or aza-Cope rearrangements. It is accepted that the term aza-Claisen should be reserved only for those processes in which a carbon atom in the allyl vinyl ether system has been replaced by nitrogen357. Three different types of aliphatic 3-aza-Cope reactions which were studied theoretically are the rearrangements of 3-aza-l,5-hexadienes (610, equation 262), 3-azonia-l,5-hexadienes (611, equation 263) and 3-aza-l,2,5-hexatrienes (612, equation 264) (the latter is a ketenimine rearrangement )357. 

Figure 1.12 Schematic representation of the M4L6 cage and molecular structure of an enammonium substrate for the 3-aza Cope reaction. CAChe model of the M4L6 supramolecular assembly, encapsulating the enammonium substrate.

Metal-catalyzed Allylic Transpositions, Oxy-Cope and Aza-Cope Reactions 563... 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

In a recent study of the 3-aza-Cope reaction, Murahashi and coworkershave found that Af- 2-butenylJ-enamine 90 undergo [l,3]-sigmatropic rearrangement rather than [3,3]-rearrangement in the presence of Pd(0) and CFjCOjH. Thus, y,<5-unsaturated aldehyde 92 is formed in 60% yield from 90 (R = Me, Ph) through rearrangement and hydrolysis reactions (equation 17). 

The stable enaminone 168 undergoes an aza-Cope reaction 170 at nearly 200 °C in nitrobenzene. It may seem odd that a linear alkyne should take part in such a reaction but in fact this is not unusual. The product is an allene 171 that undergoes tautomerism to the more stable enaminone 172 then a [1,5] sigmatropic H shift before cyclising to a dihydropyridine 174. The cyclisation is formally a six electron disrotatory electrocyclic reaction 173. The solvent PhN02 oxidises 174 to the pyridine 169. 

Such efficient transmission of stereochemical information suggest that asymmetric versions of this reaction should be possible. Using a single enantiomer of 1-phenylethylamine, a single enantiomer of the aminoketone 186 was prepared and converted into the starting material 187 for the aza-Cope reaction.28 The tandem reaction sequence is the same as that for 178 to 182 but gives a single enantiomer of 188 in 94% yield and >99% ee. 

The total synthesis of (-)-strychnine 120 was accomplished using a tandem aza-Cope-Mannich reaction sequence. Amine 115 was exposed to paraformaldehyde to generate 116. This intermediate initiated the aza-Cope reaction to produce 117 and directly underwent the Mannich reaction to ultimately afford 118. Redrawing 118 gives 119 and advanced compound on the way to 120. 

Another example of a catalytic asymmetric [3,31-sigma-tropic rearrangement is the catalytic asymmetric amino allylation of aldehydes developed by Rueping and Anton-chick and recently explored by Ren and Wulff (see Scheme 17.23). In this reaction, the homoallyhc amine 96 first condenses with the aldehyde 97 giving imine 98. With the help of an acid catalyst, the i minium ion of imine 98 is formed and the cationic aza-Cope reaction can then ensue giving protected homoallylic amine 99. After treatment... 

The zwitterionic amino-Claisen rearrangement (41-44), a variant of the aza-Cope reaction (103-105), is another sigmatropic process which has been successfully employed in the synthesis of yohimbines. Mariano and his coworkers have presented designs for the synthesis of reserpine (2) and/or deserpidine (3) in which the target was envisioned as arising from jS-enaminoester 189 by... 

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