Intermolecular Regio- and Stereoselective Hetero-[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines
Changgui Zhao1, Daniel A Glazier2, Daoshan Yang1,3
1School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Abstract:
We have developed the first intermolecular hetero-[5+2] cycloaddition reaction between oxidopyrylium ylides and cyclic imines with excellent control of regio- and stereoselectivity. Surprisingly, divergent stereochemistry was observed depending on the substitution pattern of the oxidopyrylium ylide. This new reaction provides quick access to highly substituted nitrogen-containing seven-membered rings-azepanes. Notably, a broad range of oxidopyrylium ylides and cyclic imines participate in this novel hetero-[5+2] cycloaddition reaction and the cycloadducts can be readily transformed into the core skeletons of bioactive natural products. DFT calculations revealed that the cycloaddition proceeds through a stepwise pathway and the imine nitrogen atom serves as the nucleophile to initiate the cycloaddition.
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