Intermolecular sp3C-H Metalation of Non-Nucleophilic Brønsted Bases Using Simple Lewis Acids

2,6-Di-tert-butyl substituted pyridines (tBu2-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 M2X6 Lewis acids (M = Al or Ga, X = Cl, Br or I) effect intermolecular sp3C-H metalation of tBu2-py bases under mild conditions. The sp3C-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 sp3C-H heterolysis to form the C-M bond and a protonated pyridine; (ii) C-H metalation requires singly halide-bridged super-electrophilic M2X6 dimers for sufficiently low barriers. Finally, sp3C-H metalation using M2X6 is not limited to tBu2-py bases. Thus, it is important to be aware of this facile sp3C-H functionalisation when using a range of non-nucleophilic Brønsted bases.