Controlling Diastereoselectivity in the Tandem Microwave-Assisted Aza-Cope Rearrangement-Mannich Cyclization

Abstract

The first microwave-assisted version of the tandem aza-Cope rearrangement-Mannich cyclization was developed. This sequence provides acylpyrrolidines in a single synthetic step while significantly reducing reaction times as compared to analogous reactions using conventional heating. Diastereoselectivity in these reactions may be improved by increasing the size of the amine-protecting group, an observation which has not been reported previously for aza-Cope-Mannich reactions leading to monosubstituted acylpyrrolidines. Finally, in some cases, diastereoselectivity could be improved by lowering the reaction temperature.

tandem reactions - diastereoselectivity - rearrangements - cyclizations - amino alcohols

References and Notes

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