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(sp 3 )–SCF 3 coupling under redox‐neutral conditions. The synergism of organophotocatalyst 4CzIPN and BINOL‐based phosphorothiols can site‐selectively cleave tertiary sp 3 C(sp 3 )–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(sp 3 )−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.