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)(2) (OBu)-Bu-t, 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.