Tandem reactions Overman pyrrolidine synthesis

The Overman pyrrolidine synthesis is a tandem reaction, or cascade, used to generate acylpyrrolidine derivatives. This process begins with condensation of an allylic alcohol/ether-containing secondary homoallylic amine with an aldehyde, followed by an aza-Cope rearrangement and subsequent Mannich reaction. Commonly, this reaction is run in refluxing benzene with an acidic additive, such as c/-10-camphorsulfonic acid (CSA). 

Overman, L. E. Kakimoto, M. Okazaki, M. E. Meier, G. P. C-C Bond formation under mild conditions via tandem cationic aza-Cope rear-rangement-Mannich reactions. A convenient synthesis of poly substituted pyrrolidines. 

Kotlyarevskii, 1.1.., Myasnikova, R. N and Bardamova, M. I., Aminoacctylene derivatives of ben/ofuian, Izv. Akad. Nauk SSSR, 202, 1971 Chem. Ahstr.. 75,. 5.594, 1971. Overman, I.. F-., Kakimoto, M., Okazaki, M. E., and Meier, G. P., Carbon-carbon bond formation under mild conditions via tandem cationic aza-Copc rcarrangcmcnt-Mannich reactions. A convenient synthesis of polysub-stiluted Pyrrolidines, J. Am Chem Soc., 105, 6622, 1983. 

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. 

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