Stereoselective Synthesis of Spiro-2-oxabicyclo[2.2.2]octane Enabled by Ag(I)/ Brønsted Acid Relay Catalysis.

A highly stereoselective synthesis of a spiro-cineole scaffold that contains four stereogenic centers from readily accessible 2-alkynylbenzaldehydes and styrenes under very mild reaction conditions was reported. This cascade reaction involves a Ag(I)-catalyzed alkyne cycloisomerization and oxa-[4 + 2]-cycloaddition to give an oxonium intermediate which subsequently undergoes a previously unexplored 1,2-alkyl migration to access highly strained spiro-2-oxabicyclo[2.2.2]octanes in high yields with excellent stereoselectivities.