Development of a catalytic enantioselective synthesis of the guanacastepene and heptemerone tricyclic core
For nearly two decades, synthetic chemists have been fascinated by the structural complexity and synthetic challenges afforded by the guanacastepene and heptemerone diterpenoids. Numerous synthetic approaches to these compounds have been reported, but to date the application of enantioselective catalysis to this problem has not been realized. Herein we report an enantioselective synthesis of an advanced intermediate corresponding to the tricyclic core common to the guanacastepenes and heptemerones. Highlights of this work include sequential Pd-catalyzed decarboxylative allylic alkylation reactions to generate the two all carbon quaternary stereocenters, the use of ring-closing metathesis to close the A ring in the presence of a distal allyl sidechain, and a regio- and diastereoselective oxidation of a trienol ether to introduce oxygenation on the A ring.
Additional Information© 2019 Published by Elsevier Ltd. Received 12 January 2019, Revised 20 February 2019, Accepted 22 February 2019, Available online 27 February 2019. This paper is dedicated to Professor Ryan A. Shenvi on receipt of the Tetrahedron Young Investigator Award. We thank the NIH-NIGMS (R01GM080269 and postdoctoral fellowship F32GM073332 to A.M.H.), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support.
Accepted Version - nihms-1524440.pdf
Supplemental Material - 1-s2.0-S0040402019302133-mmc1.pdf