Total Synthesis of (−)-Chromodorolide B By a Computationally-Guided Radical Addition/Cyclization/Fragmentation Cascade

The first total synthesis
of a chromodorolide marine diterpenoid
is described. The core of the diterpenoid is constructed by a bimolecular
radical addition/cyclization/fragmentation cascade that unites two
complex fragments and forms two C–C bonds and four contiguous
stereogenic centers of (−)-chromodorolide B in a single step.
This coupling step is initiated by visible-light photocatalytic fragmentation
of a redox-active ester, which can be accomplished in the presence
of an iridium or a less-precious electron-rich dicyanobenzene photocatalyst,
and employs equimolar amounts of the two addends. Computational studies
guided the development of this central step of the synthesis and provide
insight into the origin of the observed stereoselectivity.