Direct insertion into the C–C bond of unactivated ketones with NaH-mediated aryne chemistry

Here, we document the reinvention of aryne chemistry with "old" o-diiodoarenes as aryne progenitors. We have established a NaH-mediated activation strategy for the generation of highly reactive aryne species in a controlled manner. The resulting arynes can efficiently participate in a C–C σ-bond-insertion reaction with unactivated ketones, which is difficult to achieve by existing methods. Density functional theory (DFT) calculations reveal that the two adjacent iodines in o-diiodoarenes play critical roles in the formation of aryne. The nucleophilic attack of hydride to the electrophilic iodine requires that the adjacent iodine act as a directing group to accelerate this process, whereas mono-substituted iodobenzene lacking the neighboring-group participation makes it difficult. The in-situ-formed enolates from ketones are proposed to adopt tetrameric aggregates to react with arynes, which accounts for the high regiochemistry for substrates with bulky substituents.