Stereoselective Synthesis of the Taxane Ring System via the Tandem Diels-Alder Cycloaddition.
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.
Winkler
Jeffrey D.
JD
Department of Chemistry, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095.
Kim
Hak Sung
HS
Kim
Sanghee
S
Ando
Kaori
K
Houk
Kendall N.
KN