Synergistic Catalysis for the Umpolung Trifluoromethylthiolation of Tertiary Ethers

The first transition-metal-free, site-specific umpolung trifluoromethylthiolation of tertiary alkyl ethers has been developed, achieving the challenging tertiary C(sp³ )-SCF₃ coupling under redox-neutral conditions. The synergism of organophotocatalyst 4CzIPN and BINOL-based phosphorothiols can site-selectively cleave tertiary sp³ C(sp³ )-O ether bonds in complex molecules initiated by a polarity-matching hydrogen-atom-transfer (HAT) event. The incorporation of several competing benzylic and methine C(sp³ )-H bonds in alkyl ethers has little influence on the regioselectivity. Selective difluoromethylthiolation of C-O bonds has also been achieved. This represents not only an important step forward in trifluoromethylthiolation but also a promising means for site-selective C-O bond functionalization of unsymmetrical tertiary alkyl ethers.