Cyclobutenone-Based Syntheses of Polyquinanes and Bicyclo[6.3.0]undecanes by Tandem Anionic Oxy-Cope Reactions. Total Synthesis of (+/-)-Precapnelladiene.

ABSTRACT

The addition of ethenyllithium derivatives to the carbonyl of dialkyl squarate-derived bicycloheptenones, e.g., 1a and 6a, initiates a low-temperature anion-accelerated oxy-Cope rearrangement to provide polyquinanes by a transannular aldol reaction of the intermediate bicyclo[6.3.0]undecadienone 4. Additional functionality is introduced by alkylation of the enolate 3 resulting from the oxy-Cope rearrangement. Phosphorylation or triflation of enolate 3 provides an entry into the bicyclo[6.3.0]undecane ring system. An application of this new methodology is demonstrated by the total synthesis of the sesquiterpene natural product (+/-)-precapnelladiene from diisopropyl squarate (10 steps, 12%).