DFT investigation of mechanism, regioselectivity, and chemoselectivity in rhodium(iii)-catalyzed oxidative cyclization of chalcones with internal alkynes†

Abstract

Density functional theory (DFT) was used to examine the mechanism, regioselectivity, and chemoselectivity in the rhodium(iii)-catalyzed oxidative cyclization of chalcones with internal alkynes. The computational findings indicate that the entire reaction comprises two fundamental catalytic cycles. Initially, the reaction undergoes the C–H activation, followed by migratory insertion, reductive elimination, and hydrolysis to form an enol, thereby completing the first catalytic cycle. Subsequently, the enol undergoes O–H deprotonation, migratory insertion, reductive elimination, hydrolysis, and retro-aldol reaction to generate the final product. In the case of asymmetric alkynes, distortion–interaction analysis indicates that the regioselectivity is influenced by steric effects during the alkyne insertion step, while the chemoselectivity for the Rh–C or Rh–O bonds is predominantly governed by spatial hindrance and electronic influence of the substrate. A linear fitting of charges in NPA (natural population analysis) for various substituents on different chalcones reveals that the charge of the starting material plays an important role in its ability to undergo a successful (4 + 1) cyclization. This study contributes to a deeper understanding of the fundamental reaction mechanisms and offers significant insights for the rational design of related catalytic processes.