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

Abstract

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 (TPTþ) 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 Csp3─Csp3 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.