%0 Journal Article
%T Direct Benzylic C-H Etherification Enabled by Base-Promoted Halogen Transfer.
%A Bone KI
%A Puleo TR
%A Delost MD
%A Shimizu Y
%A Bandar J
%J Angew Chem Int Ed Engl
%V 0
%N 0
%D 2024 Jun 27
%M 38937258
%F 16.823
%R 10.1002/anie.202408750
%X We disclose a benzylic C-H oxidative coupling reaction with alcohols that proceeds through a synergistic deprotonation, halogenation and substitution sequence. The combination of tert-butoxide bases with 2-halothiophene halogen oxidants enables the first general protocol for generating and using benzyl halides through a deprotonative pathway. In contrast to existing radical-based pathways for C-H functionalization, this process is guided by C-H acidity trends. This gives rise to new synthetic capabilities, including the ability to functionalize diverse methyl(hetero)arenes, tolerance of oxidizable and nucleophilic functional groups, precision site-selectivity for polyalkylarenes and use of a double C-H etherification process to controllably oxidize methylarenes to benzaldehydes.