A density functional theory (DFT) study was performed to understand detailed mechanisms for the Rh(III)-catalyzed coupling reaction of phenylnitrone with diphenylacetylene in different reaction conditions. The reaction proceeds via five sequential steps, including arene C–H activation, alkyne insertion, oxygen atom transfer (OAT), protonolysis, and C–C bond coupling. Among the five steps, protonolysis is the rate- and diastereoselectivity-determining step. Furthermore, the effect of pivalic acid additive, solvent, and center metal of the catalyst on the diastereoselectivity and yields is investigated. The experimental observations in different conditions can be interpreted reasonably by our calculations.