DFT Insights into the mechanism of Ru(II) Catalyzed C7-selective amidation of N-pivaloylindole

The mechanism of regioselective functionalization is one of the research priorities in synthesis of indole derivatives. Density functional theory (DFT) calculations were employed to investigate the mechanism of Ru(II) chelate catalyzed selective functionalization of N-pivaloylindole investigated experimentally by Ackermann's group. Two possible mechanisms were carefully examined in the regioselective C - H ac-tivation, selectivity of direct functionalization at C2 and C7 site, the possibility of the coordination of tosylazide (TsN3). DFT results showed that favorable C7-H activation could undergo a thermodynamically stable prior competing intermediate and kinetically suitable transition state. Further mechanistic insights through distortion-interaction study and interaction region indicator (IRI) analysis were conducted to ex-plore the origin of the observed regioselectivity.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study employed DFT calculations to investigate the mechanism of Ru(II) chelate catalyzed selective functionalization of N-pivaloylindole. The results showed a favorable pathway for C7-H activation and provided mechanistic insights into the observed regioselectivity through distortion-interaction analysis and IRI analysis.