Intermolecular Sp ³ C─H Metalation of Non‐Nucleophilic Brønsted Bases Using Simple Lewis Acids

Abstract

Abstract 2,6‐Di‐ tert ‐butyl substituted pyridines ( t Bu 2 ‐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 M 2 X 6 Lewis acids (M═Al or Ga, X═Cl, Br or I) effect intermolecular sp 3 C─H metalation of t Bu 2 ‐py bases under mild conditions. The sp 3 C─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 sp 3 C─H heterolysis to form the C─M bond and a protonated pyridine; ii) C─H metalation requires singly halide‐bridged super‐electrophilic M 2 X 6 dimers for sufficiently low barriers. Finally, sp 3 C─H metalation using M 2 X 6 is not limited to t Bu 2 ‐py bases. Thus, it is important to be aware of this facile sp 3 C─H functionalisation when using a range of non‐nucleophilic Brønsted bases.