Modulating Prins Cyclization versus Tandem Prins Processes for the Synthesis of Hexahydro‐1H‐pyrano[3,4‐c]chromenes

We propose the synthesis of biologically relevant hexahydro‐1H‐pyrano[3,4‐c]chromenes, via a tandem Prins/Friedels‐Crafts process, catalyzed by BF3.Et2O, starting from (E)‐ and (Z)‐5‐phenoxypent‐3‐en‐1‐ol. The diastereoselectivity of the process is controlled by the geometry of the homoallylic alcohol. We also point out that the Prins product can be obtained in high yields and good diastereoselectivity when the reaction is promoted by AlCl3 as Lewis acid in the presence of an external nucleophile. By varying the conditions of the reaction between (E)‐ or (Z)‐5‐phenoxypent‐3‐en‐1‐ol and aldehydes, we can either access biologically relevant hexahydro‐1H‐pyrano[3,4‐c]chromenes via a tandem Prins/Friedel‐Crafts cascade or the tetrahydropyrane intermediate of the Prins process. In both cases, the products are obtained in high yields and good diastereoselectivities.