Cationic cascade cyclizations terminated by MOM ether derivatives of β-keto esters

Abstract

It has been known for some time that cationic cascade cyclizations initiated by Lewis acid mediated opening of an epoxide can be trapped by reaction with a β-keto ester. The studies reported here show that the efficiency of these cyclizations can be improved through preparation of a MOM enol ether from the β-keto ester. Furthermore, in both geranyl and farnesyl derivatives the stereochemistry of the enol ether controls formation of the major product. In both series, the E-enol ether leads to a cyclic vinylogous carbonate incorporating the oxygen originating in the ketone in the ring system, while the Z-enol ether leads to a cyclic enone incorporating the oxygen originating in the ester carbonyl group. Upon treatment with catalytic HCl, a facile rearrangement converts the enone product to the vinylogous carbonate. Because these cyclizations faithfully extend the stereochemistry of the original epoxide into multiple stereocenters, they have the potential to afford significantly more complex structures from relatively simple starting materials.