Total Syntheses of Scaparvins B, C, and D Enabled by a Key C–H Functionalization

The
clerodane diterpene family possesses an impressive range of
bioactivities and high synthetic challenge due to their unique amalgamation
of rings, stereocenters, and oxygenation. Herein, we disclose the
first total syntheses of three members, scaparvins B, C, and D, through
a route fueled by several chemoselective and carefully orchestrated
steps. One such operation is a tailored late-stage C–H functionalization
converting a carboxylic acid into a lactone through the oxidation
of a tertiary C–H bond under conditions that minimize epoxidation
of an alkene. This step, among others, afforded critical functionality
to complete the targets. In addition, use of an appropriate chiral
catalyst with a Rawal diene renders the sequence enantioselective.