Synthetic studies on halichlorine and pinnaic acid. Stereospecific preparation of the azaspiro core structure

Halichlorine and pinnaic acid are two novel marine natural products isolate d from a Japanese sponge and an Okinawan bivalve, respectively. The unique azaspiro[4,5]decane core structure present in both compounds provides a syn thetic challenge. Herein, we describe a synthetic approach to the azaspiro[ 4,5]decane core structure through an intramolecular [3 + 2] cycloaddition f ollowed by an intramolecular Michael addition and in situ isomerization to afford the azaspirocyclic core structures stereospecifically in 10 steps wi th 40% overall yield.