OVERMAN Pyrrolidine synthesis

ORTON Haloaniline rearrangement 282 OSTROMISLENSKY Butadiene synthesis 282 OVERMAN Pyrrolidine synthesis 263... 

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). 

The Overman pyrrolidine synthesis, or aza-Cope-Mannich reaction, was developed while troubleshooting a stereochemical challenge encountered by the Overman group as they pursued the amphibian alkaloid. 

In a recent expansion of the Overman pyrrolidine synthesis, Carballo, et al. were successful in the iron(IIl)-promoted formation of 3-... 

The synthetic utility of the Overman pyrrolidine synthesis has been demonstrated in various approaches to a range of alkaloids the Amaryllidaceae alkaloids, Aspidosperma alkaloids, Strychnos alkaloids, and Melodinus alkaloids are several types. 

Other academic groups have used the Overman pyrrolidine synthesis en route to complex alkaloids and other medicinally relevant compounds. The Brummond group at the University of Pittsburgh has reported the formal synthesis of (-)-FR901483 (48), an immunosuppressant isolated by researchers at Fujisawa Pharmaceuticals. In this report, Brummond incorporated a tandem cationic aza-Cope rearrangement/Mannich cyclization that proceeds via a bridgehead iminium ion. Treatment of intermediate 44... 

Overman Pyrrolidine Synthesis l-(5-Phenyl-l-propylpyrrolidin-3-yl)ethanone (58) ... 

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