Dearomatization/rearomatization model for copper-mediated quinoline N-oxide C–H functionalization†

Transition metal-catalyzed direct heteroarene C–H functionalization is a powerful strategy to access heteroarene derivatives with improved atom and step economy. In addition to commonly proposed concerted metalation deprotonation (CMD) and electrophilic aromatic substitution (S_EAr) models, we herein establish a copper-catalyzed dearomatization/rearomatization strategy for the C–H functionalization of electron-deficient heteroarenes, exemplified by quinoline N-oxides. Computational studies suggest a distinct pathway involving a 1,3-dipolar addition between quinone N-oxide and benzyl Cu(i). Subsequent deprotonation or base-assisted δ-elimination gives a borylative alkylation or alkenylation product. Nucleus-independent chemical shift (NICS) analysis confirms that dearomatization occurs in the 1,3-dipolar addition step and the deprotonation/δ-elimination process involves rearomatization. This dearomatization/rearomatization pathway provides an alternative approach to achieve C2–H functionalization of electron-deficient heteroarenes under mild conditions.