Mechanistic insight into the rhodium-catalyzed, P-directed selective C7 arylation of indoles: a DFT study

A density functional theory (DFT) study has been carried out to provide insight into the reaction mechanism of the rhodium(I)-catalyzed, P-directed selective C7 arylation of indoles with aryl halides. Our calculations suggest that it is more favorable for Rh(PPh3)2OtBu, the real catalytical species for the reaction, to initially undergo C–H activation process with the indole to generate a five − membered rhodacycle intermediate than to proceed through oxidative addition with the aryl halide to yield a Rh(III) intermediate. Subsequently, the sequential C(aryl)−C(aryl) reductive elimination and catalyst regeneration progresses produce the final 7−arylindole product. The first C–H activation process is identified as rate- and regioselectivity-determining step with an energy barrier of 26.0 kcal/mol. The underlying origins and factors responsible for C7- vs C2-, C3-, and C6-regioselectivity is revealed by noncovalent interaction analysis. The results declare that the reaction characters weak interaction and chelate effect-controlled regioselectivity. Our study provides important mechanistic insights for the dehydrogenative cross-coupling reaction between indoles with aryl halides, and guides the design of efficient Rh-based catalyst for C–H functionalization of indoles.