Cope rearrangements 2-azonia

The 2,4-ct.v relation of the hydroxy and the ester function in both isomers is explained by a cyclization reaction with simultaneous formation of a dioxycarbocation, presumably via a preceding 2-azonia-Cope rearrangement. Treatment with water then provides the observed... 

The 2-azonia analog of the Cope rearrangement is estimated to be accelerated by 106, relative to the unsubstituted system.270 The product of the rearrangement is an isomeric iminium ion, which is a mild electrophile. In synthetic applications, the reaction is often designed to generate this electrophilic site in a position that can lead to a cyclization by reaction with a nucleophilic site. For example, the presence of a 4-hydroxy substituent generates an enol that can react with the iminiun ion intermediate to form a five-membered ring.271... 

Entry 6 is analogous to a silyl ketene acetal rearrangement. The reactant in this case is an imide. Entry 7 is an example of PdCl2-catalyzed imidate rearrangement. Entry 8 is an example of an azonia-Cope rearrangement, with the monocylic intermediate then undergoing an intramolecular Mannich condensation. (See Section 2.2.1 for a discussion of the Mannich reaction). Entry 9 shows a thioimidate rearrangement. 

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term aza-Claisen should be reserved only for those processes in which a carbon atom in the allyl vinyl ether system has been replaced by nitrogen357.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. 

Azonia-Cope rearrangement in N-acylimi-nium cyclizations. J. Org. Chem. 1986, 51, 1687-1691. 

Iminium ions (16) and (17) were shown to be interconverted by a 2-azonia-Cope rearrangement. The position of equilibrium was found to favour (16) strongly, but the... 

Azomethinium ylids, N-metalated -, syntheses with - 43, 904 Azonia-Cope rearrangement-Mannich cyclization 41, 938, 982 lif-Azonine ring, 2,3,4,5,8,9-hexa-hydro-, 5-aryl-, N-protected 44, 579 Azoxy compds. 44, 18 Azulen-2-ones, hydro- 43, 640 Azulen-4-ones, perhydro-l-methylene-43, 955... 

A process that has been popularized and utilized extensively by Overman and coworkers involves a tandem 2-aza-Cope rearrangement followed by trapping of the resultant isomer by a Mannich reaction. First demonstrated in 1979, this has become a powerful methodology that has found substantial utility in alkaloid synthesis. " The reaction between 215 and benzaldehyde results in formation of iminium ion 217, which undergoes the 2-azonia-Cope rearrangement to give iminium ion 218. Trapping of 218 by the enol functionality results in pyrrolidine 219. 

Azepine 8 was formed by an aminoprenylation, which involves a 2-azonia-Cope rearrangement of an iminium ion, followed by reductive amina-tion of intermediate 7 to form the seven-membered ring (13OBC7507). 

Rueping and Antonchick [51] have examined the phosphoric acid diester-catalyzed 2-aza-Cope rearrangement [52], a transformation that provides an efficient entry to chiral homoallylic amines. They assumed that a phosphoric acid diester would both promote the in situ formation of an allyl iminium cation from an aldehyde and an achiral homoallylic amine, and the subsequent 2-azonia-Cope rearrangement. In a separate hydrolysis step, the rearranged homoallylic amine would furnish the target chiral amine (Scheme 40.42). 

In the presence of a Lewis acid, / ,y-unsaturated ketones and oximes or imines undergo nucleophilic addition to give zwitterionic intermediates, and subsequent oxy-2-azonia-Cope rearrangements give homoallylic amides (Scheme 23). ... 

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