A Tandem Prins/Friedel‐Crafts Cyclization Strategy for the Stereoselective Synthesis of Hexahydro‐2H‐benzo[g]chromenes

Abstract A tandem Prins/Friedel‐Crafts cascade strategy has been developed for the synthesis of hexahydro‐2 H ‐benzo[ g ]chromene derivatives. Under action of equimolecular amount of BF 3 etherate, δ,ϵ‐unsaturated alcohols and arylacetaldehydes are coupled to form oxocarbenium ion intermediates, which are captured by the alkene moiety through a favored six‐membered transition state. The Prins‐cyclization resultant tertiary carbenium ions undergo consecutive intra molecular Friedel–Crafts cyclization to create the tricyclic products. This process enables a tandem formation of three new chemical bonds in one single operation with high yields and stereoselectivity in most cases. When cyclic substituents are involved, a variety of spiro derivatives could also be synthesized successfully, which further proved the robustness of this methodology.