Part 2: Efficient strategies for the construction of variably substituted bicyclo[5.3.1]undecenones (AB-taxane ring systems) and their conversion to tricyclo[9.3.1.0~(3'8)]pentadecenones (ABC taxane ring systems) and bicyclo[2.2.2]octanones

摘要

The extension of our strategies for the construction of cyclic molecules containing variably substituted bicyclo[5.3.l]undecenones (AB taxane ring systems) for the synthesis of the tricyclo[9.3.l.0~(3-8)]pentadecenone (ABC taxane ring system) and bicyclo[2.2.2]octanones are described.These routes employ a multi-component coupling protocol that employs sequential magnesium-mediated carbometallation of allyl-substituted propargyl alcohols followed by diastereoselective Lewis acid catalyzed intramolecular Diels-Alder reactions (IMDA).Subsequent ring-closing metathesis (RCM) afforded the ABC taxane core structure.Enone accelerated [3,3] sigmatropic rearrangements (Cope rearrangements) generated the bicyclo[2.2.2]octanone nucleus.In the presence of a Lewis acid,the dienophile precursor underwent a tandem reaction via the adduct directly to the bicyclo[2.2.2]octanones.This is the first example of a novel enone accelerated carbocycle Cope rearrangement and provides direct access to bicyclo[2.2.2]octanones by a new route that compliments the traditional cyclohexadiene cycloaddition approach.