Photocatalytic Polyene Cyclization to Cyclopentyl Thioethers with Consecutive Quaternary Centers in Fluorinated Alcohols

The synthesis of carbocycles bearing consecutive all‐carbon quaternary centers remains a formidable challenge in organic chemistry due to their steric congestion and synthetic inaccessibility. Herein, an efficient and sustainable photocatalytic strategy for the cyclization of polyenes to cyclopentane thioethers using 2,4,6‐triphenylpyrylium tetrafluoroborate (TPT + ) as a photocatalyst in 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) is reported. The transformation proceeds via a thiyl radical‐initiated mechanism, forming multiple bonds and quaternary centers in a single step under mild conditions. The method tolerates a broad range of aliphatic and functionalized thiols and exhibits high yields and good diastereoselectivities, the latter strongly depending on the addressed mechanism of the transformation. Mechanistic investigations support a radical pathway initiated by thiol oxidation. This work highlights the potential of combining photocatalysis with microstructured solvent systems to facilitate polyene cyclizations. Overall, it provides a versatile platform for synthesizing sterically congested, biologically relevant carbocyclic frameworks.