eCite Digital Repository

The role of hypervalent iodine(iii) reagents in promoting alkoxylation of unactivated C(sp3)-H bonds catalyzed by palladium(ii) complexes


Abdolalian, P and Tizhoush, SK and Farshadfar, K and Ariafard, A, The role of hypervalent iodine(iii) reagents in promoting alkoxylation of unactivated C(sp3)-H bonds catalyzed by palladium(ii) complexes, Chemical Science, 12, (20) pp. 7185-7195. ISSN 2041-6520 (2021) [Refereed Article]

PDF (Published version)

Copyright Statement

2021 The Author(s). Published by the Royal Society of Chemistry. This article is an open acceee article under the Creative Commons Attribution 3.0 Unported (CC BY 3.0) license (

DOI: doi:10.1039/d1sc01230d


Although Pd(OAc)2-catalysed alkoxylation of the C(sp3)H bonds mediated by hypervalent iodine(III) reagents (ArIX2) has been developed by several prominent researchers, there is no clear mechanism yet for such crucial transformations. In this study, we shed light on this important issue with the aid of the density functional theory (DFT) calculations for alkoxylation of butyramide derivatives. We found that the previously proposed mechanism in the literature is not consistent with the experimental observations and thus cannot be operating. The calculations allowed us to discover an unprecedented mechanism composed of four main steps as follows: (i) activation of the C(sp3)H bond, (ii) oxidative addition, (iii) reductive elimination and (iv) regeneration of the active catalyst. After completion of step (i) via the CMD mechanism, the oxidative addition commences with an X ligand transfer from the iodine(III) reagent (ArIX2) to Pd(II) to form a square pyramidal complex in which an iodonium occupies the apical position. Interestingly, a simple isomerization of the resultant five-coordinate complex triggers the Pd(II) oxidation. Accordingly, the movement of the ligand trans to the PdC(sp3) bond to the apical position promotes the electron transfer from Pd(II) to iodine(III), resulting in the reduction of iodine(III) concomitant with the ejection of the second X ligand as a free anion. The ensuing Pd(IV) complex then undergoes the CO reductive elimination by nucleophilic attack of the solvent (alcohol) on the sp3 carbon via an outer-sphere SN2 mechanism assisted by the X anion. Noteworthy, starting from the five coordinate complex, the oxidative addition and reductive elimination processes occur with a very low activation barrier (ΔG 06 kcal mol−1). The strong coordination of the alkoxylated product to the Pd(II) centre causes the regeneration of the active catalyst, i.e. step (iv), to be considerably endergonic, leading to subsequent catalytic cycles to proceed with a much higher activation barrier than the first cycle. We also found that although, in most cases, the alkoxylation reactions proceed via a Pd(II)Pd(IV)Pd(II) catalytic cycle, the other alternative in which the oxidation state of the Pd(II) centre remains unchanged during the catalysis could be operative, depending on the nature of the organic substrate.

Item Details

Item Type:Refereed Article
Keywords:palladium, DFT calculation, reaction mechanism, hypervalent iodine reagents
Research Division:Chemical Sciences
Research Group:Physical chemistry
Research Field:Catalysis and mechanisms of reactions
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the chemical sciences
UTAS Author:Ariafard, A (Associate Professor Alireza Ariafard)
ID Code:150051
Year Published:2021
Funding Support:Australian Research Council (DP180100904)
Web of Science® Times Cited:5
Deposited By:College Office - CoSE
Deposited On:2022-05-16
Last Modified:2022-08-18
Downloads:9 View Download Statistics

Repository Staff Only: item control page