An Approach to a Bislactone Skeleton: A Scalable Total Synthesis of (±)-Penifulvin A

An efficient and
scalable total synthesis of the architecturally
challenging sesquiterpenoid (±)-penifulvin A has been accomplished
via a 12-step sequence with an overall yield of 16%. For the construction
of this structurally complex tetracyclic molecule, the key steps used
included 1,4-conjugate addition, a Pd(0) catalyzed cross-coupling
reaction between an enol phosphate and trimethyl aluminum, Claisen
rearrangement using the Johnson orthoester protocol, Ti­(III)-mediated
reductive epoxide opening–cyclization, Lewis acid catalyzed
epoxy-aldehyde rearrangement, and finally a substrate controlled oxidative
cascade lactonization process.