Density functional theory calculations are used to study the reaction mechanism and origins of C2-selectivity in a rhodium-catalyzed arylation of indole. It is shown that the reaction is catalyzed by an anionic Rh(III)-intermediate that activates the substrate through a concerted-metalation deprotonation. Dissociation of pivalic acid and subsequent reductive elimination generate the arylated indole product. Oxidative addition of the aryl iodide and a subsequent ligand exchange regenerates the active catalytic species. The origin of the regioselectivity is found to be the more favorable interaction between the 2-indolyl fragment and the metal center compared to the 3-indolyl fragment. Moreover, the better interaction of the pivalate ligands with the substrate in the transition state for the activation of C2-H compared to the transition state for the C3-H activation further favors the C2-selectivity.
Mechanism and selectivity of rhodium-catalyzed C-H bond arylation of indoles
Santoro, Stefano
;
2018
Abstract
Density functional theory calculations are used to study the reaction mechanism and origins of C2-selectivity in a rhodium-catalyzed arylation of indole. It is shown that the reaction is catalyzed by an anionic Rh(III)-intermediate that activates the substrate through a concerted-metalation deprotonation. Dissociation of pivalic acid and subsequent reductive elimination generate the arylated indole product. Oxidative addition of the aryl iodide and a subsequent ligand exchange regenerates the active catalytic species. The origin of the regioselectivity is found to be the more favorable interaction between the 2-indolyl fragment and the metal center compared to the 3-indolyl fragment. Moreover, the better interaction of the pivalate ligands with the substrate in the transition state for the activation of C2-H compared to the transition state for the C3-H activation further favors the C2-selectivity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
