Cationic Cascade for Building Complex Polycyclic Molecules from Simple Precursors: Diastereoselective Installation of Three Contiguous Stereogenic Centers in a One-Pot Process

An expedient strategy
for the synthesis of polycyclic small molecules
is described. The method first joins together two achiral building
blocks (an enyne and an aldehyde or a ketone) using an alkynyl halo-Prins protocol. Then, in the same reaction vessel,
acidic conditions initiate a cationic cascade that includes a stereospecific halo-Nazarov electrocyclization and a diastereoselective
Friedel–Crafts allylation. The entire sequence forms three
carbon–carbon bonds and a carbon–halogen bond, generating
halocyclopentene adducts in one pot from simple precursors. The process
occurs with excellent diastereocontrol, providing highly functionalized
polycycles containing three tertiary or quaternary stereogenic centers
in a linear array. It is even possible to install three contiguous
all-carbon quaternary centers using this method.