Intermolecular Sp³C─H Metalation of Non-Nucleophilic Bronsted Bases Using Simple Lewis Acids.

ABSTRACT: 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.

SUBMITTER: Schellbach AV 

PROVIDER: S-EPMC12377440 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature