ABSTRACT Hypervalent iodine(III) reagents are widely used in Pd‐catalyzed C─H functionalization, yet their efficacy varies dramatically with the acyloxy group. This DFT study elucidates the mechanistic origins of the reactivity differences among PhI(OAc) 2 , PhI(OCOCF 3 ) 2 , and PhI(OPiv) 2 in a C(sp 3 )–H alkoxylation. All three systems are found to follow a unified pathway involving the oxidative addition of an acyloxy radical to a Pd(II) center, followed by concerted metalation‐deprotonation (CMD) for C─H cleavage and a final S N 2‐type reductive elimination. PhI(OAc) 2 delivers the highest yield due to an optimal radical dissociation energy (17.9 kcal/mol) and the lowest CMD activation barrier (19.7 kcal/mol). In contrast, the strong electron‐withdrawing nature of the trifluoroacetoxy groups significantly elevates the radical dissociation energy of PhI(OCOCF 3 ) 2 to 38.1 kcal/mol, rendering oxidant activation the rate‐determining step. For PhI(OPiv) 2 , the pivalate group's weak trans effect destabilizes the CMD step (21.2 kcal/mol). These findings provide a mechanistically grounded electronic rationale for acyloxy‐group effects in this MIA (2‐ M ethoxy i mino a cyl)‐directed model alkoxylation system and may offer qualitative guidance for related Pd‐catalyzed C(sp 3 )–H alkoxylation reactions.
Liu et al. (Wed,) studied this question.