Paquette LA,
*,
Sun L.-Q,
Watson TJ. N,
Friedrich D,
Freeman BT.
The Ohio State University, Columbus, USA
Bridgehead Oxiranyl Sesquiterpenoids. Asymmetric Total Synthesis of (–)-Salsolene Oxide.
J. Am. Chem. Soc. 1997;
119: 2767-2768
DOI:
10.1021/ja964221
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.
