Synthesis of o-benzyl benzamides via NaH-mediated aryne insertion into N-sulfonylacetimidates

Abstract

o-Benzylbenzoic acid derivatives are valuable synthetic intermediates, but conventional syntheses suffer from limited functional group tolerance and dependence on transition metals. Herein, we report a NaH-mediated strategy for preparing o-benzyl benzamides via regioselective aryne insertion into the C–C bond of N-sulfonylacetimidates. This pathway diverges from classical benzimidate-forming routes, directly affording valuable amide products in a single step. Readily available o-diiodoarenes generate arynes in situ under NaH/THF conditions. The reaction exhibits excellent functional group compatibility. This transition-metal-free protocol not only provides an efficient and practical access to o-benzylbenzoic acid derivatives through a proposed hydrolytic mechanism but also represents a significant advancement in aryne chemistry by enabling a previously elusive direct synthesis of amides via C–C bond insertion, offering a new disconnection strategy for arene functionalization.