Mechanistic Insight into the 2° Alcohol Oxidation Mediated by an Efficient CuI/L-Proline-TEMPO Catalyst—A Density Functional Theory Study

Abstract

Density functional theory (DFT) calculations have been performed to investigate the 2 • alcohol oxidation to acetophenone catalyzed by the Cu I /L-Proline-2,2,6,6-tetramethylpiperidinyloxy (TEMPO) catalyst system. Seven possible pathways (paths A→F) are presented. Our calculations show that two pathways (path A and path B) are the potential mechanisms. Furthermore, by comparing with experimental observation, it is found that path A-in which substrate alcohol provides the proton to − O t Bu to produce HO t Bu followed by the oxidation of substrate directly to product acetophenone by O 2-is favored in the absence of TEMPO. Correspondingly, path B is likely to be favored when TEMPO is involved. In path B, the O-O bond cleavage of Cu I-OOH to Cu II-OH species occurs, followed by acetophenone formation assisted by ligand (L) 2−. It is also found that the cooperation of ligand (L) 2− and TEMPO plays an important role in assisting the formation of the product acetophenone in path B.

Mechanism of Aerobic Alcohol Oxidation Mediated by Water‐Soluble CuII‐TEMPO Catalyst in Water: A Density Functional Theory Study

“…On the contrary, the H atom transfer from alcohol to the oxygen atom of TEMPO was supported by Wu et al ,. and our previous papers ,. As a consequence, both possibilities are considered in this work.…”

Unraveling the Mechanism of Aerobic Alcohol Oxidation by a Cu/pytl-β-Cyclodextrin/TEMPO Catalytic System under Air in Neat Water

“…Until now, the substrate oxidation process, catalyzed by the Cu II /TEMPO catalysts using organic solvents, is still controversial. (To the N atom: Baerends, , Stahl, and Szpilman groups; To the O atom: Wu , and our groups. , ) Then, the question is where does the H atom go when water is used as the solvent. Thus, we considered both possibilities.…”

“…The critical intermediate of the Brückner’s substrate oxidation process is the TEMPO...O 2 -Cu II -alkoxide intermediate due to the interaction between TEMPO and O 2 and the lack of an interaction between Cu and TEMPO . Moreover, the possibilities of the H atom migration from the C α –H bond of alkoxide to the nitrogen atom ,− or oxygen atom − of TEMPO were supported by different research groups. Then, the question is which mechanism is preferred for this Cu II /(pytl-β-CD) catalyst that uses water as the only solvent and how does water affect the mechanism?…”

“…(To the N atom: Baerends, 25,26 Stahl, 21 and Szpilman 27 groups; To the O atom: Wu 28,29 and our groups. 30,31 ) Then, the question is where does the H atom go when water is used as the solvent. Thus, we considered both possibilities.…”

Recent advances in computational studies on Cu-catalyzed aerobic reactions: cooperation of copper catalysts and dioxygen

“…7). 27 The initial RO-H activation is enabled by t BuO − via 1 TS9 with an energy barrier of 17.7 kcal mol −1 . Then, the endo-on coordi-nation of O 2 generates triplet Cu II complex 3 19.…”