A DFT study of hydride transfers to the carbonyl oxygen of DDQ

Abstract

Hydride‐transfer reactions between benzylic substrates and 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) were investigated by DFT (density functional theory) calculations. The lowest unoccupied molecular orbital of DDQ has the largest extension on two carbonyl oxygens, which comes from two‐step mixing of antisymmetric orbitals of fragment π MOs. Transition‐state (TS) geometries and activation energies of reactions of four benzylic substrates R2CH2‐para‐C6H4R1 (R1, R2 = H and/or OCH3) with DDQ were calculated. M06‐2X/6‐311(+*)G* was found to be a practical computational method, giving energies and geometries similar to those of M06‐2X/6‐311++G(3df,2pd) and wB97xD/6‐311++G(3df,2pd). For toluene (R1 = R2 = H), an initiation‐propagation model was suggested, and the calculated kinetic isotope effect k(H)/k(D) = 5.0 with the tunnel correction at the propagating step is in good agreement with the experimental value 5.2. A reaction of para‐MeOC6H4CH2(OMe) + DDQ + (H2O)14 → para‐MeOC6H4C(O)H + HOMe + DDQH2 + (H2O)13 was investigated by M06‐2X/6‐311(+*)G*. Four elementary processes were found and the hydride transfer (TS1) is the rate‐determining step. The hydride transfer was promoted by association with the water cluster. The size of the water cluster, (H2O)n, at TS1 was examined. Three models of n = 14, 20, and 26 were found to give similar activation energies. Metal‐free neutral hydride transfers from activated benzylic substrates to DDQ were proposed to be ready processes both kinetically and thermodynamically. © 2015 Wiley Periodicals, Inc.

N‐Aryl Groups Are Ubiquitous in Cross‐Dehydrogenative Couplings Because They Stabilize Reactive Intermediates

“…This suggests that the transition state has a substantial biradical character derived from the proposed radical ions RI , which in turn suggests that the single electron transfer step is in fact on the reaction pathway. The biradical nature of the transition state is consistent with the proposed mechanism and contrary to a recently published model for a similar oxidation, in which a hydride transfer was proposed ,…”

Empirical Valence Bond Simulations Suggest a Direct Hydride Transfer Mechanism for Human Diamine Oxidase

“… 36 − 41 We note that it has been recently shown, both experimentally and computationally, that C–H hydrogen bond donors directly transfer the hydride anion to the carbonyl oxygen of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, which is often used model quinone in mechanistic studies. 42 , 43 Moreover, copper-promoted hydride transfer to a carbonyl group was previously reported as well. 44 Therefore, we modeled the reaction where Cα–H hydride cleavage from the histamine substrate involves a direct transfer of the hydride anion (H – ) to the carbonyl O5-atom of the TPQ cofactor ( Figure 2 ).…”

“…We therefore examined other mechanistic possibilities. Our previous computational work on the related enzyme, MAO B, makes a one electron (radical) pathway highly unlikely; we therefore focused on the direct hydride transfer from the substrate Cα–H moiety to the DAO cofactor, which is analogous to the mechanism proposed for the MAO-catalyzed oxidative deamination of amine substrates. − We note that it has been recently shown, both experimentally and computationally, that C–H hydrogen bond donors directly transfer the hydride anion to the carbonyl oxygen of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, which is often used model quinone in mechanistic studies. , Moreover, copper-promoted hydride transfer to a carbonyl group was previously reported as well . Therefore, we modeled the reaction where Cα–H hydride cleavage from the histamine substrate involves a direct transfer of the hydride anion (H – ) to the carbonyl O5-atom of the TPQ cofactor (Figure ).…”

Experimental and Theoretical Studies on the Mechanism of DDQ-Mediated Oxidative Cyclization of N-Aroylhydrazones

“…Theoretical studies on the hydrogen abstraction processes by DDQ in various C–H bond activation reactions have recently been reported, , suggesting that hydrogen can form a bond to either C or O of DDQ depending on the reaction condition. , These reports indicate that DDQ plays a larger role in the oxidation reaction than the initial single-electron oxidant . Inspired by these reports, we thought that a detailed theoretical mechanistic study for the oxidative cyclization of N -aroylhydrazones by DDQ might be useful for an understanding of the traditional DDQ-promoted oxidation as well as recent C–H activation reactions.…”

“…Theoretical studies on the hydrogen abstraction processes by DDQ in various C−H bond activation reactions have recently been reported, 58,59 suggesting that hydrogen can form a bond to either C or O of DDQ depending on the reaction condition. 60,61 These reports indicate that DDQ plays a larger role in the oxidation reaction than the initial single-electron oxidant.…”