Total Synthesis of (–)-Salsolene Oxide

Key words

(–)-salsolene oxide - Finkelstein reaction - [2+2] cycloaddition - oxy-Cope rearrangement - bridge-head olefin

Significance

In 1997, Paquette and co-workers demonstrated a [2+2] cycloaddition in a complex setting. The phenyl thioether plays a crucial role in controlling reactivity and stereoselectivity of the [2+2] cycloaddition. Blocking of the endo face during vinyllithium addition enables an anionic oxy-Cope rearrangement. Moreover, the bridge-head olefin is isomerized to the desired geometry during reductive cleavage.

Comment

The synthesis exploits a ketene–olefin [2+2] cycloaddition to yield a bicyclo[3.1.1]heptane skeleton. A stereoselective addition of vinyl lithium to ketone F triggers an anionic oxy-Cope rearrangement furnishing eight-membered ring enolate H which was smoothly trapped with methyl iodide. Late-stage Prilezhaev reaction installs the bridge head epoxide. Final deprotection and elimination yields (–)-salsolene oxide in a total of 13 steps.

Publication History

Article published online:
20 September 2022