Metal‐free Hydroalkoxylation‐Formal [4+2] Cycloaddition Cascade for the Synthesis of Ketals

A transition metal free, acid promoted cascade hydroalkoxylation–formal [4+2] cycloaddition of various alkynols with salicylaldehyde is demonstrated for the synthesis of tetrahydrofurano/pyrano‐chromenes and spiroketals. In general, alkynols underwent hydroalkoxylations in an endo‐dig manner when internal alkynes were used to furnish the heteroannular ketals, whereas terminal alkynes proceeded in an exo‐dig fashion leading to spiroketals. The study revealed that intramolecular hydroalkoxylation of alkynols is a preferred path over a generation of oxonium ions when coupling partner is salicylaldehyde. This metal‐free transformation provides a new avenue for the stereoselective synthesis of tetrahydrofurano‐ and pyrano‐chromenes in an expeditious manner. Cascading chromenes: Lewis/Brønsted acid mediated stereoselective synthesis of chromene ketals is demonstrated. The cascade reaction involved transition‐metal‐free hydroalkoxylation of alkyne and formal [4+2] cycloaddition with salicylaldehyde. Complex scaffolds like bis‐chromene, quinoline‐fused chromene, core of xyloketal and paecilospirone natural products could be assembled using this method. The study suggested that substituents on alkyne govern exo versus endo mode of hydroalkoxylation of alkynols to furnish polycyclic heteroannular or spirocyclic chromene ketals.