Base-Promoted Benzylic C-H Amination Reactions Across a Wide pKa Spectrum Enabled by 2-Halobenzofuran and -Indole Oxidants.

We disclose a base-promoted method to directly couple benzylic C-H bonds of alkyl(hetero)arenes with aniline pronucleophiles using 2-halobenzofurans and -indoles as novel halogen oxidants. We also extend this reactivity to the dual use of hexamethyldisilazide (HMDS) reagents as bases and nucleophilic ammonia surrogates to access primary benzyl amines via a simple deprotection and isolation protocol. This methodology leverages halogen transfer (X-transfer) reactivity to merge deprotonation, halogenation, and nucleophilic substitution into one synergistic process that is critical for reaction success. Here, a thermodynamically uphill deprotonation event generates transient benzyl carbanionic and halide intermediates which circumvent well-known complications of dimerization in metalation-halogenation sequences and amine overalkylation from benzyl halide substitution. These features enable novel scope and selectivity opportunities over traditional C-H metalation chemistry and established radical- or nitrene-based C-H amination strategies. With reactivity guided by C-H acidity trends, this protocol is effective for polyalkylarenes, hard-to-oxidize alkyl(hetero)arenes, and substrates with oxidation-prone functional groups that are unsuitable or unselective in alternative mechanistic approaches. New benzofuran and indole X-transfer reagents (XTRs), which are compatible with amine nucleophiles and bases, allow the expansion of X-transfer oxidative coupling to a substantially wider pKa range than previously accessible. Structural studies of these easily-prepared reagents explain their enhanced productivity for C-H amination and provide guidelines for their continued application to other oxidative C-H coupling reactions.