Intermolecular SpC─H Metalation of Non-Nucleophilic Brønsted Bases Using Simple Lewis Acids.

2,6-Di-tert-butyl substituted pyridines (Bu-py) are widely used non-nucleophilic Brønsted bases. Their ubiquity is due to their highly hindered basic site and chemically robust nature. Herein we report that simple MX Lewis acids (M═Al or Ga, X═Cl, Br or I) effect intermolecular spC─H metalation of Bu-py bases under mild conditions. The spC─H metalated products can be converted in situ into ─BPin, ─iodo, ─bromo and ─hydroxy derivatives for further elaboration. Mechanistic investigations indicate that: i) a frustrated Lewis pair effects spC─H heterolysis to form the C─M bond and a protonated pyridine; ii) C─H metalation requires singly halide-bridged super-electrophilic MX dimers for sufficiently low barriers. Finally, spC─H metalation using MX is not limited to Bu-py bases. Thus, it is important to be aware of this facile spC─H functionalisation when using a range of non-nucleophilic Brønsted bases.