Counterion Effect on the Mechanism of Gold(I)-Catalyzed Cycloisomerization of 3-Allenylmethylindoles to 4,9-Dihydro-1H-Carbazoles: A Computational Study

A detail computational investigation of the mechanism of the title reaction has been carried out with density functional theory (DFT) method to make clear the role of counterion and the regiochemistry of the initial nucleophilic attack of the indole core on the alkylating agent (i. e. C2 vs C3 position). The calculated results suggest that 6-endo-trig cyclization followed by bistriflimide counterion-assisted proton transfer could account for the formation of the final product. In other words, intramolecular nucleophilic attack by C2 of the indole group towards the terminal carbon atom of the allene moiety leads to the formation a 6-membered ring fused indolyl intermediate, which undergoes deprotonation and protodemetallation to give the final product. Of the three steps, the rate determining step of the whole catalytic cycle is the deprotonation step with an activation free energy of 14.4 kcal/mol. It is also found that the regiochemistry of the initial nucleophilic attack of the indole moiety on the cationic gold-activated allene moiety is dependent on the conformation of reactant complex, the nature of substituent in the allene moiety and the size of phosphine ligand.

Automated summary

A detailed computational investigation using density functional theory was conducted to elucidate the mechanism of the title reaction, highlighting the crucial role of counterion and regiochemistry. The study found that the rate determining step of the entire catalytic cycle is the deprotonation process, while the nucleophilic attack position of the indole moiety depends on the conformation of the reactant complex and the nature of substituent in the allene moiety.