Factors Influencing the Chemoselectivity of Pd(OAc) 2 -Catalyzed Cyclization Reactions Involving 1,6-Enynes as a Substrate and PhI(OAc) 2 as a Reagent.

It is well documented in the literature that 1,6-enynes are cyclized using PhI(OAc) 2 (PIDA) in the presence of Pd(OAc) 2 as a catalyst to yield cyclopropyl ketones. In contrast, it has been reported that when 1,6-enynes are substituted by a hydroxy group at the α-position to the alkyne, the chemoselectivity of the cyclization reaction is altered, and polycyclic oxa-heterocycles are formed. This suggests that the hydroxy substituent plays a crucial role in changing the mechanism of the reaction. The aim of this study is to use density functional theory (DFT) calculations at the SMD/M06-D3/def2TZVP//SMD/M06/SDD,6-31G(d) level of theory to shed light on the reason for this change by investigating the detailed mechanistic aspects of these transformations. This study demonstrates that the electronic nature of the Pd catalyst changes from π-philicity to oxophilicity during the catalytic cycle, and this change plays an essential role in controlling the chemoselectivity of the cyclization reactions. In addition, it was found that (1) the hypervalent iodine reagent PIDA serves not only as an oxidant for the oxidation of Pd(II) to Pd(IV), but also as a nucleophile that drives the acetoxypalladation step of the reaction, (2) the oxidation of Pd(II) to Pd(IV) by the iodonium ion [PhIOAc] + occurs via an interesting mechanism involving coordination of [PhIOAc] + to the Pd(II) centre, followed by a twist in the hypervalent iodine, and (3) Pd π-complexes are not very susceptible to oxidation. (4) A Pd(II) complex can be six coordinate if the Pd centre is partially oxidized.