A unified mechanistic framework for DDQ-promoted transformation of electron-deficient alkenes: the addition-coupled electron transfer (ACET) perspective

Abstract

2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ) is a widely used oxidant in organic chemistry, but the mechanism of DDQ-promoted transformation of electron-deficient alkenes has remained unclear. We elucidate a unified mechanistic framework for the reactions of DDQ with a diverse range of alkene substrates utilizing high-level computations and various experiments, including kinetics measurements, linear free energy relationships, and isotopic effects. Contrary to the prevailing SET paradigm, we demonstrate that these transformations are initialized by addition of DDQ to alkenes. Critically, this addition operates on a mechanistic continuum between classical electrophilic addition (AdE2) and a newly recognized elementary step termed addition-coupled electron transfer (ACET). A zwitterionic intermediate is generated in the AdE2 regime, while a biradical intermediate is generated in the ACET one by concurrent nucleophilic addition and electron transfer. The position of a reaction on the ACET–AdE2 continuum is governed by the electronic properties of alkene substrates and the extent of acid catalysis. By integrating high-level DLPNO-CCSD(T) and NEVPT2 calculations with multiple experimental probes, we provide a computational–experimental dissection of these mechanisms with state-of-the-art accuracy. Although DDQ is the focus here, this unified framework is not restricted to DDQ: the ACET–AdE2 continuum is likely general for a broad class of oxidants. Most importantly, this study deepens our understanding of ACET as a new elementary step in organic reactivity, using DDQ as a representative case. This work not only resolves the long-standing mechanistic ambiguity in DDQ-involved reactions but also challenges the prevailing SET dogma and establishes ACET as a general principle of chemical reactivity.

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Introduction

2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ) is a versatile oxidant,^1,2 enabling diverse transformations, including C–H bond amination,^3,4 C–C coupling,^5,6 oxidation of alcohols,^7–9 and organic photo- or electrosynthesis.^10–13 Therefore, its utility extends across multiple chemical disciplines: it serves as a protecting/deprotecting reagent in organic methodology,¹⁴ a specialized catalyst for coupling reactions in total synthesis,¹⁵ a polymerization agent in biological chemistry,¹⁶ and an analytical tool in pharmaceutical product examinations.¹⁷ In most of these contexts, the oxidative mechanism has been simplified as either electron transfer to DDQ—producing radical cation intermediates—or hydrogen abstraction or hydride transfer. While direct oxidation is plausible for electron-rich substrates, it is far less likely for electron-deficient alkenes bearing electron-withdrawing groups. Despite the diversity of DDQ-promoted chemistry, comprehensive computational studies of these assumed electron transfer pathways remain scarce. The few existing works^4,18,19 rely exclusively on density functional theory (DFT), which may lack sufficient accuracy when multireference character is significant. Moreover, these studies have not explored alternatives beyond the conventional SET pathway, thereby limiting their scope to electron-rich systems or substrates with abstractable hydrogen atoms.

Since 2021, we have advanced the concept of a new elementary step—addition-coupled electron transfer (ACET).^20–22 In ACET, electron transfer from the alkene to an oxidant is coupled with nucleophilic addition to the alkene within a single elementary step. This synergistic interplay between addition and electron transfer enables reactions between inactivated alkenes and weak nucleophiles—a scenario where independent nucleophilic addition would be thermodynamically unfavorable. The oxidant facilitates SET, typically in the pre-transition state region, thereby opening a new pathway to the oxidized addition product.

While our previous works established ACET as a theoretical concept and identified its possible occurrence in specific systems, the generality, experimental observability, and quantitative features of ACET have remained unexplored. A key challenge has been to determine whether ACET represents merely an isolated mechanistic curiosity or a broadly applicable elementary step in the world of chemistry.

In the present work, we move beyond conceptual proposals and limited case studies by identifying an experimentally tractable platform—DDQ-promoted alkene transformations—as a general manifestation of the ACET mechanism. The present work is motivated not only by the need to clarify the long-debated mechanisms of DDQ-promoted reactions, but also by the broader goal of deepening our mechanistic understanding of ACET itself as a newly recognized elementary reaction step. To this end, we employ both high-level multireference computations and experimental validation (kinetics, LFER, and isotope effects), offering a combined perspective beyond standard DFT approaches. Thus, while we focus on DDQ as a representative case, the mechanistic framework and insights we propose are likely applicable to a wider family of oxidants and other reactions. Through this system, we demonstrate that ACET operates across multiple reactions, revealing its general mechanistic scope and its continuum with classical AdE2 pathways, and achieve the experimental measurement of the structure–reactivity relationship and linear free-energy behavior of an ACET process for the first time.

Our work examines three representative reactions from the literature to elucidate the distinctions between the AdE2 and ACET mechanisms. Jin (2020)²³ reported a tandem Friedel–Crafts/ring-expansion reaction of benzylidene fluorene derivatives (e.g., Jin1) with arenes in the presence of DDQ and trifluoroacetic acid (TFA) or a dichloroethane (DCE)/TFA mixture yielding 9,10-diarylphenanthrenes. The reaction temperatures ranged from room temperature to reflux, depending on arene reactivity. Kim (2014)²⁴ reported DDQ-promoted oxidative cyclization reactions of electron-deficient carbonyl-substituted alkenes (e.g., Kim1 or Kim2) in DCE at 60 °C with methanesulfonic acid (MsOH), affording substituted naphthalenes. The possible mechanisms of these reactions are thoroughly investigated using high-level domain-based local pair natural orbital coupled cluster theory (DLPNO-CCSD(T))^25–27 and N-electron valence state second-order perturbation theory (NEVPT2)²⁸ calculations, complemented by experimental data. We suggest that these reactions proceed not via SET but through the addition of DDQ to the substrate. Such addition reactions exhibit characteristics spanning a continuum from ACET to AdE2, depending on the electronic properties of substrates and the presence of acid molecules. We thus propose a unified framework for rationalizing otherwise compartmentalized DDQ-promoted transformations of electron-deficient alkenes. This dual emphasis—on resolving the mechanistic ambiguity of DDQ chemistry and on expanding the conceptual scope of ACET—allows us to propose a unified framework for rationalizing otherwise compartmentalized DDQ-promoted transformations, while highlighting ACET as a general principle of reactivity beyond DDQ. By framing ACET–AdE2 as a mechanistic continuum, we not only provide a new lens for DDQ chemistry but also challenge the entrenched SET paradigm that has dominated for decades (Fig. 1).

Fig. 1 (a) Typical DDQ-promoted oxidative transformations of deficient alkenes and their previously believed mechanisms. (b) Schematic concept of ACET and the key mechanism proposed in this work.

Computational methods

All density functional theory (DFT) calculations were performed using Gaussian 16.²⁹ Based on benchmark studies, the M06-2X functional³⁰ with the def2-SVP basis set³¹ was chosen for geometry optimization. Frequency calculations were performed at the same level and Gibbs free energy corrections at 298.15 K were obtained using Grimme's quasi-rigid-rotor harmonic oscillator (quasi-RRHO) method³² implemented in the GoodVibes program.³³ The concentration was set to be 13.1 M for TFA and 1.0 M for other species. For Kim's reactions, the SMD implicit solvation model³⁴ with DCE as the solvent was employed. For Jin's reaction, due to the lack of optimized solvation parameters for TFA, benchmarking (see the SI for details) indicated that the integral equation formalism variant of the polarizable continuum model (IEFPCM)³⁵ with Bondi radii³⁶ was optimal, and it was therefore used.

Single-point energy calculations were performed at the DLPNO-CCSD(T) and NEVPT2 levels of theory using the def2-TZVPPD basis set³⁷ in the ORCA 6 program.³⁷ This combined approach seeks to exploit the advantages of both single-reference coupled-cluster and multi-reference methods, since the DLPNO-CCSD(T) algorithm is unavailable for open-shell singlet systems. Most single-point calculations employed DLPNO-CCSD(T). For the DDQ-addition transition states and intermediates (Jin_TS2–Jin_TS4, Jin_TS2′–Jin_TS4′, Kim1_TS2, Kim1_TS3, Kim1_TS2′, Kim1_TS3′, Kim2_TS2, Kim2_TS3, Kim2_TS2′, Kim2_TS3′, and their corresponding reactants and products), NEVPT2 calculations were performed with a 12-electron, 12-orbital active space selected based on unrestricted Hartree–Fock (UHF) natural orbitals (UNOs). All post-Hartree–Fock calculations were performed in the gas phase. The final relative free energies for NEVPT2-calculated species were defined as follows:

G = E + thermal correction + G_solv

Here, the corresponding reactant complex possesses a closed-shell singlet ground state. The solvation free energies G_solv were calculated using the universal easy solvation energy evaluation (uESE) method³⁸ (at the B3LYP/def2-TZVP level³⁹) for Kim's reactions and the IEFPCM at the B3LYP/6-31G(d) level for Jin's reactions, following the recommendations for each solvation model.

Spin density analysis was performed with the Multiwfn 3.8 program.⁴⁰ The molecular geometries and isosurfaces were depicted with CYLView⁴¹ and VMD.⁴²

Results and discussion

We investigated three representative reactions: (1) the reaction of Jin1 with anisole in TFA; (2) the cyclization of Kim1 in DCE/MsOH; and (3) the cyclization of Kim2 in DCE/MsOH. We first assessed the feasibility of the previously proposed SET mechanism involving an alkene radical cation intermediate. Cyclic voltammetry (CV, Fig. 2) and differential pulse voltammetry (DPV, Fig. S5) revealed that DDQ undergoes single-electron reduction at 0.57 V and two-electron reduction at 0.97–0.98 V in the presence of 1.0 equivalent of MsOH or in TFA. Jin1 and Kim1 exhibited irreversible oxidation behavior with peak potentials of 1.56 V and 1.80 V, respectively (determined by DPV). Thus, the proposed two-electron transfer is thermodynamically uphill (ΔG = +26.8 and +37.8 kcal mol⁻¹ for Jin1 and Kim1, respectively). Our calculations further support the unfavorable nature of the SET mechanism (Fig. 2b–d). In addition to the endergonic electron transfer, the subsequent steps in the proposed SET mechanism involve prohibitively high barriers: 26.1 kcal mol⁻¹ for the Friedel–Crafts reaction of Jin1, 42.0 kcal mol⁻¹ for the cyclization of Kim1, and 33.9 kcal mol⁻¹ for the cyclization of Kim2. While the barrier for Jin1 may seem surmountable, it is not only outcompeted by the mechanism we propose below but also inconsistent with experimental observations. Furthermore, acid-catalyzed pathways initiated by alkene protonation were previously ruled out by Kim,²⁴ and confirmed by the unfavorable free energy change of protonation (18.1 kcal mol⁻¹ for Jin1 and 35.7 kcal mol⁻¹ for Kim1). Collectively, these results argue against the SET-based mechanism.

Fig. 2 (a) CV profiles for DDQ in DCE, DCE/MsOH (1.0 eq.) and TFA as solvents, respectively, and for the selected substrates Jin1 and Kim1 in DCE. (b–d) Computed Gibbs free energy profiles for the previously believed SET-based mechanisms.

Instead, we identified a significantly more favorable pathway involving DDQ addition to the alkene. Given the use of TFA as the solvent, we examined DDQ addition assisted by zero, one, and two TFA molecules (Fig. 3a–c). In all cases, DDQ preferentially adds to the phenyl C2 atom rather than the fluorenyl C1 atom. Due to the entropic penalty associated with TFA hydrogen bonding to the DDQ oxygen, the pathway without TFA assistance exhibits the lowest barrier (18.6 kcal mol⁻¹viaJin_TS2). Notably, Jin_TS2 exhibits an open-shell singlet character (S² = 0.6120), leading to the biradical intermediate Jin_Int3. Spin density analysis (Fig. 3d) reveals C,O-biradical character localized on both the oxygen atoms of DDQ and the fluorenyl carbon atom. This biradical character suggests a mechanism distinct from typical bimolecular electrophilic addition (AdE2) as discussed in subsequent sections.

Fig. 3 (a–c) Gibbs free energy profiles for the addition of DDQ to Jin1 in the presence of 0 (a), 1 (b) and 2 (c) TFA molecules. (d) Geometries and spin densities of the key transition states (TSs). (e) Gibbs free energy profile for the further transformation into the final product JinProd.

In contrast to Jin_TS3 and Jin_TS4, the TFA-assisted pathways viaJin_TS3 and Jin_TS4 directly yield the zwitterionic intermediates Jin_Int6 and Jin_Int8, respectively, featuring a fluorenyl carbocation and a protonated phenol moiety. However, these transition states also exhibit significant C,O-biradical character (S² = 0.4041 and 0.4388 for Jin_TS3 and Jin_TS4, respectively), and no stable closed-shell wavefunction could be located. The electronic structure and its implications for reactivity are discussed below.

The observation that Jin_Int6 and Jin_Int8 exhibit only closed-shell ground states suggests that the biradical intermediate Jin_Int3 collapses into a zwitterion through intramolecular electron transfer from the fluorenyl radical to the phenol radical upon interaction with TFA. The fluorenyl carbocation undergoes a rapid Friedel–Crafts reaction assisted by two TFA molecules viaJin_TS6 and Jin_TS7, yielding the arylated intermediate Jin_Int11 with a substantial exergonicity of −42.5 kcal mol⁻¹. In the highly acidic TFA solvent, Jin_Int11 undergoes an S_N1 reaction, dissociating DDQH₂ and equilibrating with the trifluoroacetate-substituted intermediate Jin_Int13, which was isolated in Jin's original report.²³ The carbocation intermediate Jin_Int12 further undergoes 1,2-aryl migration and subsequent deprotonation viaJin_TS8 and Jin_TS9, resulting in the formation of the final product JinProd with a barrier of 28.5 kcal mol⁻¹. Overall, the computational results support a two-stage reaction: (1) rapid substrate consumption leading to the resting state Jin_Int13, with the rate determined by DDQ addition; and (2) S_N1 reaction and rearrangement of Jin_Int13, determining the rate of formation of the final product JinProd. TFA does not directly participate in the initial DDQ addition to the substrate; instead, its effect manifests after the highly reversible addition step. By stabilizing the biradical intermediate Jin_Int6 to the zwitterion Jin_Int8, it drives the equilibrium forward, enables the generation of the carbocation required by the subsequent Friedel–Crafts reaction, and also provides a critical acidic environment for the S_N1-type rearrangement reactions.

The biradical character of the key TSs and intermediates in the DDQ addition to Jin1 distinguishes this mechanism from the 2e-AdE2 one. The classical AdE2 reaction features electron transfer from the π orbitals of the alkene to the π* orbitals of DDQ. This two-electron process (2e-AdE2, illustrated by the arrow-pushing scheme in Fig. 4a) typically generates a zwitterionic intermediate. However, this pathway cannot account for the observed biradical species. An alternative mechanism involves nucleophilic attack by the occupied orbital of DDQ O1 (Fig. 4a) on the electron-deficient alkene, forming a transient fluorenyl anion. Concurrent intramolecular single electron transfer oxidizes the fluorenyl anion, generating the biradical intermediate. This corresponds to an ACET mechanism. Additionally, the one-electron process (1e-AdE2) which generates a biradical intermediate is also possible. In this reaction, the alkene donates one of the π-bonding electrons to the DDQ moiety. Although DDQ should also donate one electron to form the new C–O bond, the alkene-to-DDQ donation should dominate at TSs because of the much smaller energy gap of the π(alkene)–π*(DDQ) interaction than that of the π*(alkene)–π or n(DDQ) interaction (Fig. S3). Detailed electronic structure analysis was then performed to distinguish the reactions between ACET and 1e-AdE2.

Fig. 4 (a) Comparison of the arrow-pushing schemes of the AdE2 and ACET reactions. (b and c) Evolution of energy, spin density on DDQ, CM5 charge on DDQ and CM5 charge on the key oxygen atom O1 along the IRC of Jin_TS2. (d) Extended Transition State – Natural Orbitals for Chemical Valence (ETS-NOCV) orbital pairs and the corresponding eigenvalues of Jin_TS2.

Although both ACET and 1e-AdE2 lead to the same product, intrinsic reaction coordinate (IRC) analysis favors the ACET mechanism. In the 1e-AdE2 pathway, the dominant interaction should be electron donation from the alkene to DDQ, which should result in excess negative charge localized on the electrophilic DDQ fragment. By contrast, the ACET pathway features a dual role of DDQ: it acts both as a nucleophile and as a single-electron oxidant. The coupling of addition and electron transfer produces a distinct, piecewise profile along the IRC.

Starting from the separated alkene and DDQ, the system remains a closed shell until a sharp increase in spin density on DDQ near the transition state, indicating an ET event. The CM5 atomic charge on O1 and the entire DDQ fragment becomes less negative before the transition state, consistent with DDQ acting as a nucleophile at this stage. This decrease in negative charge on DDQ halts abruptly at the point of electron transfer, followed by a sharp increase in negative charge in the near-TS region where DDQ accepts one electron. After the ET event is accomplished, another decrease in negative charge occurs in the post-TS region. This behavior along the IRC aligns with the ACET mechanism but not 1e- or 2e-AdE2.

The orbital interactions in Jin_TS2 further support the ACET mechanism. Extended Transition State – Natural Orbitals for Chemical Valence (ETS-NOCV) analysis reveals four major interactions between the alkene and DDQ: (1) π(alkene) donates 0.865 electrons to π*(DDQ); (2) the occupied p-orbital of O1 donates 0.213 electrons to π*(alkene); (3) the filled antibonding orbital resulting from the four-electron interaction between p(O1) and π(alkene) donates 0.389 electrons to π*(alkene); and (4) carbonyl π(DDQ) donates 0.300 electrons to π*(alkene).

Although interaction (1) reflects electron flow from the alkene to DDQ and is therefore termed “AdE2-like”, such donation is not exclusive to the AdE2 mechanism—it also occurs in ACET, where an electron transfer from the alkene to π*(DDQ) takes place near the transition state. The other three interactions, arising from DDQ-to-alkene donation, are characteristic of ACET. The summed eigenvalues for these ACET-type interactions (0.902) slightly exceed that of the alkene → DDQ component (0.865), indicating that Jin_TS2 exhibits electronic features distinct from a classical AdE2 process and characteristic of the ACET mechanism.

Combined IRC and ETS-NOCV analyses suggest that DDQ addition to Jin1 is more appropriately described by ACET than 1e-AdE2. Although the quinone lone pair is usually a quite weak nucleophile, the coupling with ET enhances its reactivity and enables the reaction, exhibiting the potential ability of ACET to activate weak nucleophiles.

Although the TFA-assisted pathway viaJin_TS3 is less favorable than the Jin_TS2 pathway, it is noteworthy because it involves a closed-shell intermediate formed via an open-shell transition state. IRC analysis (Fig. 5a) confirms closed-shell character for both the reactant and product, with significant biradical character emerging only near the transition state. ETS-NOCV analysis (Fig. 5c) shows that Jin_TS3 exhibits greater AdE2 character than Jin_TS2, while two ACET-type orbital interactions, contributing 0.463 electrons donated from DDQ to the alkene, remain significant. The mechanism can be visualized as depicted in Fig. 5b. Before the transition state, the reaction proceeds with mixed 1e-AdE2 and ACET character, leading to a C,O-biradical species. However, hydrogen bonding with TFA enhances the oxidizing ability of the phenol radical, coupling a second electron transfer within the same elementary step. The second electron transfer occurs upon reaching the transition state, leading to rapid loss of biradical character in the post-transition state region. Thus, a single nucleophilic addition event is coupled with two sequential electron transfers.

Fig. 5 (a) IRC analysis of Jin_TS3. (b) Arrow-pushing scheme for the addition of DDQ to Jin1 in the presence of hydrogen-bonded TFA. (c) ETS-NOCV analysis of Jin_TS3. (d) Marcus analysis for the transition from ACET to AdE2.

This transition from a typical ACET mechanism to a typical 2e-AdE2 mechanism, and the coupling of the two electron transfers with the addition step, can be visualized using Marcus theory with parabolic potential energy surfaces (PESs) (Fig. 5d). At the ACET limit, the biradical PES interacts effectively with both the substrate PES and the zwitterionic PES, leading to a biradical intermediate connected to the substrates via an ACET transition state, with the second electron transfer occurring in a separate step (as seen with Jin_TS2). As the second electron transfer becomes more favorable, the zwitterionic PES is lowered, and the three PESs intersect efficiently near the transition state. Here, the two-electron transfers occur sequentially within a single step, and the transition state is stabilized by mixing with the biradical PES (as seen for Jin_TS3). When the zwitterionic PES is significantly stabilized, its intersection with the substrate PES lies far below the biradical PES, leading to a classical 2e-AdE2 mechanism without biradical character.

These computational insights are supported by experimental observations. While Jin's original report used pure TFA as the solvent with heating, we found that a DCE/TFA (5 : 1) mixture allows kinetic monitoring at room temperature due to its improved substrate solubility. Consistent with computations, Jin1 is rapidly depleted within 30 minutes, while the product JinProd forms gradually over several hours. The DDQ-addition intermediate Jin_Int11 has been detected by high-resolution mass spectrometry (HR-MS, Fig. S6). Control experiments confirmed that the reaction is not light-driven, and in the absence of anisole, the substrate is fully recovered even in pure TFA at room temperature, consistent with the Friedel–Crafts reaction being the first irreversible step. A negligible kinetic isotope effect (KIE) of 1.03 was observed using TFA-d versus TFA, supporting the dominance of the non-assisted pathway viaJin_TS2.

Unfortunately, direct detection of biradical intermediates proved challenging, likely due to their high relative energy and the rapid second electron transfer. Electronic paramagnetic resonance (EPR) analysis of DDQ and Jin1 mixtures, with or without TFA, yielded no signal, and spin trapping experiments using DMPO were inconclusive due to DMPO's incompatibility with DDQ (see the SI for details). Although TEMPO was found to completely inhibit the reaction, this does not definitively confirm a radical pathway, as TEMPO may cause the reductive deactivation of DDQ. To further probe the ACET/AdE2 nature of the reaction, a Hammett study was conducted. A typical AdE2 reaction exhibits a large negative ρ value, while an ACET reaction, involving both nucleophilic attack (driving the ρ value to be positive) and single-electron oxidation (driving the ρ value to be negative) of the alkene, is expected to have a smaller ρ value. The experimental Hammett plot (Fig. 6c) revealed a moderate ρ value of −1.54. For comparison, the relative equilibrium constant (K/K_H) for single-electron oxidation of the alkene, calculated based on experimental oxidation potentials, exhibits a much larger negative ρ value of −6.75, which may be expected for an SET-based mechanism. The measured Hammett ρ value is also significantly smaller than those of some known AdE2 reactions.^43–45 This relatively small ρ value for the reaction rate supports an ACET-like mechanism over AdE2 or SET.

Fig. 6 (a) Kinetics profile for Jin1's reaction with anisole. (b) Results of controlled experiments. (c) Hammett plot for Jin1's reaction, derived by the rate of substrate consumption. (d) Linear free energy relationship between the constant of equilibrium of substrate oxidation and a substitute constant. ^a NMR yield. ^b Isolated yield.

We then extended our investigation to Kim's reported reactions. Computational results for Kim1 (Fig. 7) suggest a similar mechanistic pathway, although the stronger acidity of MsOH favors acid-assisted addition viaKim1_TS3, with an overall barrier of 26.8 kcal mol⁻¹. Like Jin's reaction, all addition transition states exhibit open-shell singlet ground states, leading to the biradical intermediate Kim1_Int5, which subsequently converts to the zwitterion Kim1_Int6. A near-barrierless cyclization follows, leading to deprotonation and formation of Kim1_Int8. An E1 elimination releases DDQH₂, and a final deprotonation yields product Kim1Prod. ETS-NOCV analysis of the key transition state Kim1_TS3 reveals contributions from both ACET-like (0.893 electrons donated from DDQ to the alkene) and AdE2-like (0.920 electrons donated from the alkene to DDQ) interactions. Although the AdE2-like interaction is slightly more pronounced than in Jin_TS2, the substantial contribution of the DDQ → alkene component still evidences clear ACET character, making this transition state somewhat more AdE2-like but still fundamentally ACET in nature.

Fig. 7 (a) Gibbs free energy profile for the reaction of Kim1 with DDQ. (b) Geometry and spin density plot for Kim1_TS3. (c) NOCV analysis for Kim1_TS3.

The reaction of Kim2, however, exhibits a different mechanism (Fig. 8). Kim2 is less electron-deficient than the other substrates due to the presence of only one carbonyl group, as evidenced by its higher HOMO energy (Fig. 9). Consequently, a classical 2e-AdE2 mechanism dominates. The MsOH-assisted addition of DDQ to the C1 site viaKim2_TS3 (with a barrier of 23.5 kcal mol⁻¹) proceeds on the closed-shell singlet PES and is characterized by a substantial 2e-AdE2-type electron donation (1.339 electrons) from π(alkene) to π*(DDQ), generating a phenyl carbocation. This carbocation does not correspond to a minimum on the PES; instead, it undergoes barrierless cyclization to form Kim2_Int5. Subsequent barrierless deprotonation, facilitated by the MsO⁻ counteranion, leads to the resting state Kim2_Int7. An E1 elimination then yields product Kim2Prod.

Fig. 8 (a) Gibbs free energy profile for the reaction of Kim2 with DDQ. (b) NOCV analysis for Kim2_TS3.

Fig. 9 HOMO levels (eV) of typical substrates and the transition from ACET to 2e-AdE2 of the related TSs.

Conclusion

Through a combination of computational and experimental evidence, we establish a unified mechanistic framework for three representative DDQ-promoted oxidative transformations of electron-deficient alkenes. Our study rules out the previously proposed SET pathway via an alkene radical cation and instead demonstrates that all reactions proceed through a sequence initiated by DDQ addition to the alkene, followed by aryl electrophilic addition, deprotonation, DDQH₂ cleavage, and a final deprotonation.

Crucially, we show that the rate-determining step in all cases is the initial DDQ addition, whose mechanistic character spans a continuum between ACET and 2e-AdE2, depending on the electronic nature of the substrate and the extent of acid catalysis (Fig. 9). This continuum is governed by the intersection of three PESs: the closed-shell, zwitterionic, and biradical surfaces (Fig. 5d). For electron-rich alkenes under strong acid catalysis, stabilization of the zwitterionic PES favors a classical 2e-AdE2 mechanism without biradical involvement, as exemplified by Kim2. In contrast, increasing electron deficiency progressively balances the zwitterionic and biradical PESs, giving rise to transition states with partial biradical character and coupled sequential electron transfers (e.g., Jin1_TS3). For strongly electron-deficient alkenes or under weaker acid catalysis (as in Kim1 and Jin1_TS2, or in the non-acid-assisted pathways of Kim2), the biradical PES dominates, resulting in an ACET-dominating pathway characterized by strong orbital interactions between DDQ and the alkene coupled with single electron transfer.

This unified mechanism is supported by various experimental findings, including the observed biphasic kinetics profile, direct HR-MS detection of DDQ-addition intermediates, negligible KIEs (consistent with non-acid-assisted pathways), and moderate Hammett correlations that disprove SET. Beyond clarifying these long-standing mechanistic ambiguities, our work introduces the concept of an ACET–2e-AdE2 mechanistic continuum as a general framework for DDQ-promoted oxidations. We anticipate that this paradigm will extend to a much broader class of transformations of electron-deficient alkenes and even to systems mediated by other organic or metal-based oxidants, thereby providing new design principles for oxidative transformations.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information: computational method benchmarking data, supplementary tables and figures, experimental procedures and compound characterization, Cartesian coordinates and energetics for all the species involved. See DOI: https://doi.org/10.1039/d5qo01444a.

Acknowledgements

Computational resources, the Gaussian license and compound characterization were provided by Hangzhou Yanqu Information Technology Co., Ltd. Yumiao Ma acknowledges Wi Sugar and all students in the Department of Chemistry, Tsinghua University, for their generous support, love, and encouragement. Special acknowledgements go to Prof. Ming-Tian Zhang and Mr. Yu-Hua Guo (Tsinghua University) for their help with electrochemical measurements.

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