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-2Hbenzo[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.

Synthesis of Thienyl Polycyclic Fused Indoles Based on the Indium Catalyzed Prins/Friedel‐Crafts Tandem Reaction

“…In 2022, Wang and co‐workers developed the synthesis of hexahydro‐2H‐benzo[g]chromenes from δ,ϵ‐unsaturated alcohols and aryl acetaldehyde promoted by 1.0 equiv. of BF 3 ⋅ Et 2 O [21] . So far, to the best of our knowledge, this type of reactions with catalytic amount of Lewis acid have not been realized yet.…”

“…of BF 3 • Et 2 O. [21] So far, to the best of our knowledge, this type of reactions with catalytic amount of Lewis acid have not been realized yet. Based on our continuous research interest in constructing heterocyclic compounds through tandem cyclization reactions and our recent interest in thiophene derivatives, we have constructed a series of thienyl-substituted hexahydrofurocyclopenta [1,2-b]indoles by catalytic modified Prins/Friedel-Crafts tandem cyclization between thienyl homoallylic alcohols and indole aldehydes using 10 mol% of indium triflate as catalyst.…”