1,2-Oxygen Transposition on Arenes Enabled by Palladium/Norbornene Cooperative Catalysis

Phenols and their derivatives widely exist in bioactive molecules, and the position of phenolic oxygen can greatly influence their bioactivities. Thus, strategies that allow efficient relocation of oxygen substituents on arenes would be highly valuable for generating novel analogues, which would otherwise require laborious de novo synthesis. However, the current oxygen-1,2-transposition approach is limited to para -substituted phenols bearing electron-donating groups. Here we report a complementary approach for 1,2-oxygen migration on arenes, enabled by palladium/norbornene cooperative catalysis. This method shows complete regioselectivity and tolerates substrates with various electronic properties and substitution patterns. While ortho -substituted substrates work the best, preliminary success with ortho -unsubstituted phenols has been achieved, leading to an interesting “OH-scan” across three contiguous positions. Further, late-stage 1,2-transposition of phenolic oxygen in three pharmaceutically relevant compounds was successfully demonstrated.