The asymmetric synthesis of the cladiellin diterpene natural
product (+)-polyanthellin A is described. The core tetrahydrofuran
was constructed using a stereospecific and stereoselective (3+2)-annulation
of a donor-acceptor cyclopropane and a labile β-silyloxy
aldehyde. These particular reactants necessitated the application
of a new Lewis acid, MADNTf2 [(ArO)2AlNTf2],
to avoid competitive elimination. Ring-closing metathesis was employed
to form the oxonane ring at C3-C4 and give a functional
group handle that could be elaborated to the natural product.
annulation - total synthesis - heterocycles - Lewis acids - ring opening
