Mechanistic Details of the Sharpless Epoxidation of Allylic Alcohols—A Combined URVA and Local Mode Study

Abstract

In this work, we investigated the catalytic effects of a Sharpless dimeric titanium (IV)–tartrate–diester catalyst on the epoxidation of allylalcohol with methyl–hydroperoxide considering four different orientations of the reacting species coordinated at the titanium atom (reactions R1–R4) as well as a model for the non-catalyzed reaction (reaction R0). As major analysis tools, we applied the URVA (Unified Reaction Valley Approach) and LMA (Local Mode Analysis), both being based on vibrational spectroscopy and complemented by a QTAIM analysis of the electron density calculated at the DFT level of theory. The energetics of each reaction were recalculated at the DLPNO-CCSD(T) level of theory. The URVA curvature profiles identified the important chemical events of all five reactions as peroxide OO bond cleavage taking place before the TS (i.e., accounting for the energy barrier) and epoxide CO bond formation together with rehybridization of the carbon atoms of the targeted CC double bond after the TS. The energy decomposition into reaction phase contribution phases showed that the major effect of the catalyst is the weakening of the OO bond to be broken and replacement of OH bond breakage in the non-catalyzed reaction by an energetically more favorable TiO bond breakage. LMA performed at all stationary points rounded up the investigation (i) quantifying OO bond weakening of the oxidizing peroxide upon coordination at the metal atom, (ii) showing that a more synchronous formation of the new CO epoxide bonds correlates with smaller bond strength differences between these bonds, and (iii) elucidating the different roles of the three TiO bonds formed between catalyst and reactants and their interplay as orchestrated by the Sharpless catalyst. We hope that this article will inspire the computational community to use URVA complemented with LMA in the future as an efficient mechanistic tool for the optimization and fine-tuning of current Sharpless catalysts and for the design new of catalysts for epoxidation reactions.

Systematic Development of Vanadium Catalysts for Sustainable Epoxidation of Small Alkenes and Allylic Alcohols

“…Backed by experimental and computational studies (Figure 13) it constitutes an interesting advantage when harnessing lability for overlapping chemical benefits from both strategies at a reduced cost. A recent study on mechanistic insights of this example is provided by Freindorf [109], claiming that after the activation of the vanadium(IV) complex, these two competitive processes may occur, corroborating previous theoretical explanations by Calhorda [29]. While one path is considered an "outer sphere path" with an external attack of the olefin at the coordinated peroxide, the other, an "inner sphere mechanism", is based on the vanadium catalyst complex with a coordinated substrate.…”

Reaction mechanism – explored with the unified reaction valley approach

“…Typically, only a few components at a given path position s contribute to the curving of the reaction path, which allows for the analysis of larger chemical reactions more feasible. 108,137,142–147…”

“…Typically, only a few components at a given path position s contribute to the curving of the reaction path, which allows for the analysis of larger chemical reactions more feasible. 108,137,[142][143][144][145][146][147] Originally, the decomposition of k(s) into B ms (s) coefficients was performed, following the MHA's RPH protocol. 109,122,130,133,148 However, it turned out that such a decomposition, while it gives important information for laser enhancement of reaction rates or energy decomposition into vibrational modes, 109 is of limited use for the decoding of the actual reaction mechanism, in particular in the case of larger systems, since the B ms (s) are based on normal vibrational modes (see eqn (8)).…”

Mechanism of the Sharpless Epoxidation Reaction: A DFT Study

“…A few years ago, we reported a series of TSs for the epoxidation of Ti-bound allyl alcohol where the Ti­(IV) catalyst is composed of the bidentate­(R,R)-(+)-diethyl tartrate chiral auxiliary and tert -butyl hydroperoxide that are the basic reactants in the Sharpless epoxidation . More recently, Freindorf and Kraka have reported the Ti­(IV)-catalyzed methyl hydroperoxide epoxidation of allyl alcohol employing an amide modification of the diethyl tartrate. This study used the unified reaction valley approach (URVA) and local mode analysis to describe the intricate motions and energetics of bond making of the oxygen transfer step.…”