Temporary Silicon Tether Strategy for Palladium-Catalyzed C-H Activation Reactions

A palladium-catalyzed intramolecular ortho C–H arylation of phenols has been developed. This methodology features the employment of a removable silicon tether strategy, allowing both TBDPS and a newly developed Br-TBDPS protecting groups to serve as efficient aryl group donors for arylation of phenols. Along this line, this removable silicon tether strategy was further applied to the intramolecular arylation of bisaryloxysilanes for the preparation of unsymmetrical ortho-biphenols, ortho-binaphthols, and mixed ortho-phenol-naphthols. We have also developed a silanol-directed, palladium-catalyzed C–H alkenylation of phenols. Thus, employment of silanol as a traceless directing group is very convenient as it can easily be installed and removed under mild conditions. This alkenylation method is general, as it tolerates a variety of differently substituted phenols and diverse electron-deficient alkenes. The synthetic usefulness of this novel transformation was demonstrated in the efficient synthesis of benzofuranone derivative. Furthermore, the application of this method to the olefination of estrone showcased the viability of this method for the late-stage modification of bioactive molecules for drug discovery. Mechanistic studies supported an electrophilic pathway for the C–H activation step. We have also shown that silanol can direct palladium-catalyzed C–H oxygenation of phenols en route to catechols. This protocol is highly site selective and general, as it allows for efficient oxygenation of phenols regardless of their electronic properties. Mechanistic studies indicated that this C–H oxygenation reaction undergoes ortho C–H acetoxylation first, the product of which is then converted into the cyclic silyl-protected catechol via a transesterification/cyclization sequence mediated by the in situ generated acetic acid.