Asymmetric Total Synthesis of Clionastatins A and B.

Herein we report the first total synthesis of polychlorinated steroids clionastatins A and B, which was accomplished asymmetrically by means of a convergent, radical fragment coupling approach. Key features of the synthesis include an Ireland-Claisen rearrangement to introduce the C5 stereocenter (which was ultimately transferred to the C10 quaternary stereocenter of the clionastatins via a traceless stereochemical relay), a regioselective acyl radical conjugate addition to join the two fragments, an intramolecular Heck reaction to install the C10 quaternary stereocenter, and a diastereoselective olefin dichlorination to establish the synthetically challenging pseudoequatorial dichlorides. This work also enabled us to determine that the true structures of clionastatins A and B are in fact C14 epimers of the originally proposed structures.