Stereoselective Synthesis of the Taxane Ring System via the Tandem Diels-Alder Cycloaddition.

Abstract

The application of the tandem Diels-Alder cycloaddition to the stereoselective synthesis of the tricyclic ring system of the taxane diterpenes is described. The exceedingly direct, two-step synthesis of the B/C cis-fused taxane nucleus in 50% overall yield from the reaction of two readily available acyclic precursors underscores the efficiency of this approach. A critical feature of the second, intramolecular Diels-Alder cyclcoaddition is the transmission of stereochemical information across the taxane framework, i.e., from the C ring to the A ring. The cycloaddition of both cis- and trans-disubstituted C ring constructs leads to the establishment of the requisite C-1/C-3 relative stereochemistry for the synthesis of taxanes. A computational model is presented to account for the high levels of asymmetric induction observed in these reactions.