Asymmetric Total Synthesis of (−)-Pavidolide B via a Thiyl-Radical-Mediated [3 + 2] Annulation Reaction

The development of an efficient strategy for the asymmetric
total
synthesis of the bioactive marine natural product (−)-pavidolide
B is described in detail. The development process and detours leading
to the key thiyl-radical-mediated [3 + 2] annulation reaction, which
constructed the central C ring with four contiguous stereogenic centers
in one step, are depicted. Subsequently, the seven-membered D ring
is constructed via a ring-closing metathesis reaction followed by
a Rh­(III)-catalyzed isomerization. This strategy enables the total
synthesis of (−)-pavidolide B in the longest linear sequence
of 10 steps.