Model Studies Toward the Enantioselective Synthesis of Perhydrohistrionicotoxin: A Free-Radical Approach to the Azaspirocycle Core

Abstract A free-radical-based protocol for the construction of the azaspirocyclic core of the natural product perhydrohistrionicotoxin is described. The adopted strategy is based on the use of an enantiomerically pure allylamine bearing a properly substituted cyclohexane at the allylic position as a radical acceptor. An unexpected reductive atom transfer radical addition reaction, followed by lactamization and removal of the chiral auxiliary is achieved in a single manipulation.