Theoretical Investigation of the Mechanism of the Hock Rearrangement with InCl₃ as Catalyst**

Abstract

The Hock rearrangement is an acid catalyzed reaction involving organic hydroperoxides and resulting in an oxidative cleavage of adjacent CÀ C bonds. It has significant industrial applications, like the production of phenol (cumene process), but it remains scarcely used in organic synthesis. In addition, its detailed mechanism has never been studied. Thus, we report herein a theoretical study of the Hock rearrangement, using InCl 3 as a Lewis acid catalyst. The aim of this work was to fully understand the mechanism of this fundamental reaction, and to rationalize the influence of the substrate electronic properties on the reaction outcome. Furthermore, the structure of the active indium(III) catalyst interacting with the peroxide substrate was investigated, revealing the co-existence of several energetically close reaction pathways. The coordinated monomeric form of the Lewis acid emerges as the most active catalyst compared to dimeric species. However, we show that In 2 Cl 6 species coordinated to the substrate are central in this catalytic cycle, primarily serving as a reservoir of active monomeric species.

Tandem InCl3-Promoted Hydroperoxide Rearrangements and Nucleophilic Additions: A Straightforward Entry to Benzoxacycles

“…From a mechanistic point of view regarding the InCl 3 -promoted Hock rearrangement, this experimental study opens interesting questions on the influence of the substituents on the hydroperoxide rearrangement, the catalytic character of InCl 3 and the nature of the active metallic species, or the preferential migration of the sp 2 carbon compared to the sp 3 carbon. These questions, of a more fundamental nature, have been the subject of a theoretical investigation in a separate article . Based on this study and previous hypotheses concerning the Hosomi–Sakurai allylation, we propose a mechanism for the present tandem transformation (Scheme ).…”

“…The use of catalytic amounts of BF 3 ·OEt 2 (0.1 equiv) was inefficient (no reaction, entry 3). Although the Hock rearrangement was observed with pTsOH (entry 4) or TMSOTf (entry 5), only bis­(peroxyacetal) 4a was identified (see ref for a discussion of the structure determination), demonstrating the elimination and recombination of peroxide species during these reaction, while no reaction occurred with catalytic amounts of (PhO) 2 PO 2 H (entry 6). Catalytic amounts of Sn­(OTf) 2 , In­(OTf) 3 , Sc­(OTf) 3 , and AlCl 3 mostly led to complex mixtures of products (entries 7–10), but trace amounts of 2a (3%) could be detected with In­(OTf) 3 .…”

“… a Note that InCl 3 is always coordinated and does not exist in a free monomeric form (see ref for details). …”

“…Recently, we investigated the mechanism of the InCl 3 -catalyzed Hock rearrangement through theoretical chemistry, detailing the formation of the oxocarbenium intermediate through a Wheland intermediate . Considering the electrophilicity of hypothetical oxocarbenium intermediates, the Hock and Criegee rearrangements can be considered as potential candidates to design interrupted versions by tandem additions of various nucleophiles − (route C).…”

Tandem Hock and Friedel-Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

“…Recently, we applied this idea to the rearrangement of 1-indanyl hydroperoxides into 2-substituted chromane derivatives, involving the nucleophilic allylation of the rearranged oxocarbenium intermediate (Scheme 1b) [12,13]. Furthermore, it is interesting to mention that allylic hydroperoxides are conveniently produced by the photooxygenation of alkene substrates [14 -16].…”