A New Methodology for Ring Enlargements by the Oxy-Cope Rearrangement: Ready Access to Highly Functionalized Medium-Size Rings

Highly functionalized cyclononenones, -decenones and -undecenones 14-19 were prepared via a sequence of twofold Heck reaction on 1,2-dibromocycloalkenes 1-3 to yield (E,Z,E)-1,3,5-hexatrienes 4-6, subsequent epoxidation of the central double bond leading to the formation of epoxides 7-9, reductive ring opening of the epoxides and oxyanion-accelerated Cope rearrangement. The stereochemical outcome of the rearrangements was highly dependent on the ring size and, particularly in the case of the cyclodecenones, on the reaction conditions. Moreover, these transformations proved to be the first examples of reversible anionic oxy-Cope rearrangements. Conversions in the presence of benzyl halides led to formation of benzylated cycloalkenones 28-31 via a domino process of rearrangement and alkylation on an intermediate enolate.

benzylation - hydrogenolysis of epoxides - oxyanionic Cope rearrangements - ring expansion - medium-size rings