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.