Controlled meta-Selective C–H Mono- and Di-Olefination of Mandelic Acid Derivatives

Mandelic acids represent a key structural motif present in many drug molecules. Herein, we report the controlled meta-selective mono- and diolefination of mandelic acids by the careful design of the substrate and oxidant. Furthermore, free meta-functionalized mandelic acid was generated by selectively removing the template under mild basic conditions. The synthesis of functionalized homatropine and cyclandelate drug derivatives was demonstrated. Kinetic isotope effects revealed C–H activation as the rate-limiting step.