Mechanistic Investigation of Visible-Light-Induced Intermolecular [2+ 2

Article pubs.acs.org/JPCA

Mechanistic Investigation of Visible-Light-Induced Intermolecular [2 + 2] Photocycloaddition Catalyzed with Chiral Thioxanthone Yimeng Yang,†,‡ Yongqiang Wen,† Zhimin Dang,†,§ and Haizhu Yu*,‡ †

Department of Polymer Science and Engineering, University of Science and Technology Beijing, Beijing 100083, PR China Department of Chemistry and Center for Atomic Engineering of Advanced Materials, Anhui University, Hefei 230601, PR China § State Key Laboratory of Power System and Department of Electrical Engineering, Tsinghua University, Beijing 100084, PR China ‡

S Supporting Information *

ABSTRACT: The recent thioxanthone-sensitizer-catalyzed intermolecular [2 + 2] cycloaddition induced by visible-light irradiation set the stage for the future development of feasible photocycloadditions. Nonetheless, the mechanism of this reaction still remains under debate, especially on the activation mode of the thioxanthone photosensitizer (energy transfer, bielectron exchange, and hydrogen transfer are all possible mechanisms). To settle this issue, systematic density functional theory calculations have been carried out. The results indicate that the energy-transfer pathway is more favorable than the bielectron-exchange and the hydrogen-transfer pathways. Meanwhile, the overall transformations involve the complexation and excitation of photosensitizer, the first C−C bond formation, the dissociation of the sensitizer, the triplet-to-singlet electronic state crossing, and the second C−C bond formation. The first C−C bond formation is the rate- and selectivity-determining step, and synergistic energy and electron transfer from photosensitizer to substrate moieties takes place along this process. On this basis, the effect of olefin substrates (ethyl vinyl ketone vs vinyl acetate) on the stereoselectivity was finally analyzed. Scheme 1. [2 + 2] Photocycloaddition Reported by Bach32

1. INTRODUCTION Cyclobutanes are ubiquitous in natural products1−4 and are useful building blocks/therapeutic agents in drug design.5−7 In view of atom-economy, [2 + 2] cycloaddition represents an ideal strategy to construct cyclobutane frameworks.8,9 Specifically, the photoinduced [2 + 2] cycloaddition (i.e., photocycloaddition) receives increasing attention in organic synthesis10−12 and pharmaceutical chemistry13−19 because its conditions are environment-friendly and the reaction procedures are easily handled. However, a major challenge of the photochemical [2 + 2] cyclization is the control of the stereoselectivity, as the racemic products are generated in most cases.20 Recently, different strategies, such as the direct photoexcitation,21−23 energy transfer with photosensitizer,24 and photoredox catalysis25−27 have been successfully used to accomplish the enantioselective [2 + 2] photocyclizations. Compared with the conventional photosensitization strategy requiring the ultraviolet/near-ultraviolet (UV/NUV) lights, the recently developed photocyclizations using the visible-light resources appear highly attractive for practical applications.28−31 In particular, Bach and coworkers recently synthesized a novel chiral thioxanthone sensitizer (TX1, Scheme 1) and found its extraordinarily catalytic activity in promoting the enantioselective intramolecular [2 + 2] cycloadditions under visible-light irradiation (Scheme 1a).30,31 In addition, with this photosensitizer catalyst, they further © XXXX American Chemical Society

achieved versatile intermolecular [2 + 2] photocycloaddition of 2(1H)-quinolones with electron-deficient olefins under visible light (Scheme 1b).32 The good substituent tolerance and the high enantioselectivity (with ee value up to 95%) demonstrate the high synthetic potential of this new catalyst. Interestingly, using electron-rich olefin (such as vinyl acetate), Received: March 29, 2017 Revised: May 5, 2017 Published: May 29, 2017 A

DOI: 10.1021/acs.jpca.7b02995 J. Phys. Chem. A XXXX, XXX, XXX−XXX

Article

The Journal of Physical Chemistry A

could benefit deep understandings for enantioselective [2 + 2] photocycloadditions and broaden the application of thioxanthone photosensitizer.

the stereoselectivity was remarkably lowered and an exo/endo mixture was gained. According to the structural characteristics of TX1 and the previous proposals, three typical mechanisms might be plausible to interpret the catalytic activity of TX1 in the [2 + 2] cycloadditions (Scheme 1). First, as suggested by Bach and coworkers in the similar photosensitizer-catalyzed reactions, an energy-transfer mechanism might occur. In this mechanism (denoted as energy-transfer mechanism, Scheme 2a), TX1 first

2. METHODS All DFT calculations were performed with Gaussian09 program.40 Following the recent mechanistic studies on photosensitization reactions,41−45 we used the hybrid Becke3LYP (B3LYP) functional46,47 to optimize the geometry of all species. The 6-31G* basis set was used for all atoms.41,42 MeCN was used to model the experimentally used PhCF3 solvent due to the absence of the solvation parameters for PhCF3 in Gaussian software, employing the polarizable continuum model (PCM) solvation model.48,49 Frequency calculations were carried out at the same level of theory to provide the thermochemistry analysis and to confirm that the number of imaginary frequency of intermediate and transition states is 0 and 1, respectively. Intrinsic reaction coordinates (IRCs)50−53 were used to confirm the relationship between the transition-state structures and the related intermediates on potential energy surface. The different configurations of each species have been taken into account, and the most stable one is used for the following discussions.54−56 In this study, the Gibbs free energies were used to describe all of the reaction energetics.57 All of these energies correspond to the reference state of 1 mol/L, 298 K. Meanwhile, the effect of different functionals (such as M06-2X58 and PBE59,60) was tested for the excitation energies of TX1 and 2(1H)-quinolone. All of these methods give consistent conclusions, and the details are provided in the Supporting Information (SI).

Scheme 2. Illustrative Diagrams of (a) Energy Transfer, (b) Bielectron Exchange, and (c) H-Transfer Mechanisms

binds with R1 via the hydrogen bonding. After that, light excites the formed complex, and the inner energy transfer from the photosensitizer to the substrate moiety generates the triplet substrate.32,33 Second, the synchronous double electron-transfer mechanism reported by Dexter34 is also plausible for the sensitization process of TX1. As shown in the bielectron transfer mechanism in Scheme 2b, the exchange of two electrons between the excited-state TX1* and the ground-state substrate R1 occurs to generate the excited-state R1* and TX1 (i.e., one electron transfers from TX1* to R1, and the other electron transfers from R1 to TX1*). Third, in the reactions of triplet excited-state thioxanthen-9-one with indole reported by Ji et al.,35 the hydrogen-transfer mechanism has been proposed to account for the thioxanthone deactivation process. According to this mechanism, the hydrogen atom may transfer from R1 to TX1* to initiate the radical type transformations (H-transfer mechanism, Scheme 2c). Herein, the accurate activation/deactivation mode of this novel chiral photosensitizer is still a controversial issue and needs to be elucidated. Meanwhile, some other questions, such as the origin and determinant parameters of the stereoselectivity, should also be ascertained. To settle the above issues, we studied the mechanism of TX1-catalyzed intermolecular [2 + 2] cyclization (Scheme 1b) with density functional theory (DFT) calculations. Our study corroborates Bach’s proposal in that the activation of TX1 occurs via the energy-transfer mechanism. The overall catalytic cycle consists of the complexation and excitation of photosensitizer, the first C−C bond formation, the dissociation of sensitizer, the riplet to singlet electronic state crossing, and the second C−C bond formation. Similar to the recently reported photoinduced [2 + 2] cyclizations,36−39 the first C−C bond formation in cycloaddition is the rate- and selectivitydetermining step. In particular, the spin density analysis demonstrates that both electron and energy transfer from the photosensitizer to the substrate moieties occur along this process. On this basis, the substituent effect of olefins on the stereoselectivity is clarified. We hope the provided insights

3. RESULTS AND DISCUSSION 3.1. Model Reaction. The TX1-catalyzed [2 + 2] photocycloaddition between 2(1H)-quinolone (R1) and ethyl vinyl ketone (R2) under visible-light irradiation is chosen as the model reaction (Scheme 3) because this reaction gives the Scheme 3. Model Reaction Used in Calculations

product exo-P1 with high isolated yield (89%) and high stereoselectivity (91% ee).32 The R1, R2, and the ground-state catalyst TX1 are chosen as the energy reference point. The carbon atoms directly participating in the cyclization are numbered as shown in Scheme 3. 3.2. Comparison of the Energy-Transfer, BielectronExchange, and H-Transfer Mechanisms. 3.2.1. EnergyTransfer Mechanism. In the energy-transfer mechanism, the complexation of TX1 with R1 first occurs via two hydrogenbond interactions (H−1O = 1.900 Å, H−2O = 1.801 Å, Figure 1) to generate Inter1a. This complexation step is slightly exergonic by 0.4 kcal/mol. Herein, the relative energy of Inter1a is overestimated due to the deficiency of B3LYP method in treating weak interaction involved processes. To this end, the B3LYP-D3 functional with the dispersion correction was used to re-examine the energy demand of this process (as B


Article


transition states and products will be discussed later. In this pathway, the intermediate Inter2a could be first formed, from which the C1−C3 bond formation occurs via the exoattack transition state TS2-3a (Figure 2). The energy barrier of this step is 11.7 kcal/mol (Inter1a* → TS2-3a → Inter3a), and the relative energy of Inter3a is lower than that of Inter2a by 17.5 kcal/mol. Thereafter, the direct C2−C4 bond formation requires a quite high barrier of 29.6 kcal/mol (Inter3a → TS3−4a), predominantly because the double unpaired electrons with the same spin direction actually repel each other. Given that the product exo-P1-anti is in singlet state, we anticipate that a triplet to singlet crossing point associated with the singlet C2−C4 bond formation could be more applicable. To this end, a minimum energy crossing point (MECP)61−64 has been successfully located (denoted as MECP1, ΔG = 52.9 kcal/mol), and the C2−C4 bond distance is ∼2.57 Å (see the SI for more details). From MECP1, the C2−C4 bond automatically forms to generate the singlet intermediate Inter4a with a continuous energy decrease. Therefore, MECP1 is formally the transition state connecting Inter3a and Inter4a, and its barrier is 4.2 kcal/mol (Inter3a → MECP1). The low energy barrier indicates that the spin crossing is quite facile. Finally, the dissociation of TX1 from Inter4a releases the cycloaddition product (exo-P1-anti) and regenerates the photosensitizer TX1. According to Figure 2, the overall activation barrier of Energy Path A is 11.7 kcal/mol (Inter1a* → TS2-3a), and the C1−C3 bond formation is the rate-determining step. In Energy Path B, the dissociation of TX1 occurs on Inter1a* via the cleavage of the double hydrogen bonding. The energy demand of this process is 1.3 kcal/mol (the related discussions on this step are provided in the SI). In the formed intermediate Inter1b*, the spin density analysis indicates that the two unpaired electrons mainly locate on the α,β-carbon atoms of the carbonyl group, resulting in the elongated C−C bond distance in Inter1b* compared with that in Inter1a* (1.455 vs 1.359 Å). From Inter1b*, the formation of C1−C3 bond is initiated by the attack of C3 atom on R2 to C1 atom on R1 (Inter2b → TS2-3b → Inter3b). The energy barrier of this step is 4.7 kcal/mol, and the energy of Inter3b is lower than

Figure 1. Optimized structures of Inter1a and Inter1a*. The bond distances are given in angstroms.

well as the other hydrogen-bond-involving process, i.e., Inter1a* → TX1+Inter1b*, vide infra). The detailed results and discussions are included in the SI. Thereafter, Inter1a could be excited to its first triplet (T1) state Inter1a* via the S1 state (ΔG = 76.5 kcal/mol) under photoirradiation. In Inter1a*, the two unpaired electrons mainly locate on the carbonyl group of the aromatic ring, indicating that the excitation mainly corresponds to the carbonyl π → π* transition. This protocol is supported by the significantly lengthened CO bond distance (C−3O in Figure 1) and the spin density analysis of Inter1a and Inter1a* (please see the SI for the details). From Inter1a*, depending on the sequence of the double C−C bond formation and the TX1 dissociation steps, different mechanisms might occur to generate the [2 + 2] cyclized product. The direct cyclization with a final TX1 dissociation mechanism is named Energy Path A, and the TX1 dissociation first pathway is named Energy Path B. The detailed energy profiles of these two pathways are given in Figure 2. In Energy Path A, the different approaching direction of R2 to Inter1a* might lead to different stereoisomeric products exo-P1-syn, endo-P1-syn, exo-P1-anti, and endo-P1-anti (Figure 3; note: endo/exo refers to the attacking direction to Inter1a* shown in Figure 1, and syn-/anti- relates to the relative location of −COEt and the heterocyclic ring in the product). Herein we mainly focus on the more favorable pathway for clarity reasons, and the details of the other

Figure 2. Energy profiles of Energy Paths A and B. Energies are given in kcal/mol. C


Article


Figure 3. Optimized structures of rate-determining transition states and products of Energy Path A−B and the other three stereoisomeric pathways.

heteroaromatic group in TS2-3a-exoanti, and thus the lessened steric hindrance results in its higher stability (compared with that of TS2-3a-exosyn). According to these results and discussion, the Energy Path A−B yielding exo-P1-anti is kinetically more favorable than the other three pathways, and exo-P1-anti is the predicted product of the energy-transfer pathway. In Path A−B, the C1−C3 bond formation occurs before the C2−C4 formation step. In our study, an alternative C2−C4/ TX1-dissociation/C1−C3 bond formation pathway has also been examined. However, the significantly higher energy of the C2−C4 bond formation transition state compared with that of TS2-3a (78.9 vs 70.4 kcal/mol) excludes such mechanistic possibility, 8.5 kcal/mol (see the SI for more details). 3.2.1.2. Detailed Electron-Transfer Mode in Energy Path A−B. The details of the electron and energy transfer is the key difference between different mechanisms (i.e., energy-transfer, bielectron-exchange, and H-transfer mechanisms). To investigate the details of electron flows in Energy Path A−B, the spin densities and the key structural parameters of Inter1a*, Inter2a, TS2-3a, and Inter3a have been examined. As shown in Table 1, the two unpaired electrons of Inter1a* and Inter2a mainly locate on the TX1 moiety. In both structures, the spin densities on TX1 and R1 parts are 1.998 and 0.002, respectively. However, with the attack of R2 to [TX1-R1]

that of Inter2b by 21.0 kcal/mol. After that, similar to the C2− C4 bond formation in Energy Path A, the large activation barrier in triplet state precludes the possibility of the triplet ring closure process via TS3−4b. Instead, the C2−C4 bond is formed via the spin crossing point (MECP2) with the formal barrier of only 0.4 kcal/mol (Inter3b → MECP2; see the SI for more details of MECP2). From MECP2, the cyclized product exo-P1-anti was produced automatically. This step is exergonic by 33.6 kcal/mol. The overall activation barrier of Energy Path B is 14.1 kcal/mol (Inter1a* →TS2-3b), and the C1−C3 bond formation is the rate-determining step (Inter1a* → TS2-3a). Note that in our study a combined pathway of Energy Path A and Energy Path B (denoted as Energy Path A−B), in which the dissociation of TX1 occurs between the double C−C bond formation steps, was also taken into account (Inter1a* → Inter2a → TS2-3a → Inter3a → Inter3b → MECP2 → exoP1-anti). Interestingly, the relatively lower energies of Inter3b and MECP2 compared with those of MECP1 indicate that the dissociation of TX1 tends to occur before the C2−C4 bond formation step. In other words, the overall transformation of energy-transfer pathway proceeds through Energy Path A−B via the complexation and excitation of TX1, C1−C3 bond formation, TX1 dissociation, triplet to singlet electronic state crossing, and C2−C4 bond formation steps. The C1−C3 bond formation is the rate-determining step, and the overall energy barrier is 11.7 kcal/mol. As mentioned above, the different approaching direction of R2 to Inter1a* leads to the different stereoisomeric products. For clarity, an illustrative diagram and the optimized structures of the key transition states have been given in Figure 3. Comparing the exo- and endoattack transition states, the ligation of TX1 on Inter1a* induces remarkable steric hindrance to preclude the endoattack mode (Figure 1). This is the reason why the relative free energies of TS2-3a-endoanti and TS2-3a-endosyn are relatively higher than those of TS23a-exoanti and TS2-3a-exosyn (74.9 vs 70.4 and 73.6 vs 72.9). Meanwhile, the bulky −COEt group is away from the

Table 1. Mulliken Spin Density and Key Bond Distances on the TX1, R1, and R2 Fragment of Relevant Stationary Point Involved in Energy Path A−B Mulliken spin density

D

compound

TX1

R1

Inter1a* Inter2a TS2-3a Inter3a

1.998 1.998 −0.004 0.001

0.002 0.002 1.642 1.023

bond length (Å)

R2

C3O

C1−C2

C3−C4

0.000 0.362 0.976

1.287 1.287 1.236 1.237

1.359 1.359 1.463 1.499

1.340 1.350 1.492


Article


might possibly occur via the stepwise electron−proton transfer pathway (Hydrogen Path A in Scheme 5) or direct hydrogen-

moiety, the Mulliken spin densities on TX1, R1, and R2 fragment in TS2-3a change to −0.004, 1.642, and 0.362, respectively. These data indicate that the two unpaired electrons on TX1 partially transfer to R1 and R2 moieties during the C1−C3 bond formation process. In the case of Inter3a, the comparable spin densities on R1 and R2 part (1.023 vs 0.976) imply that the R1 and R2 parts each have one unpaired electron. Therefore, the inner electron transfer from TX1 to R1 and then to R1&R2 moieties takes place along the C1−C3 bond formation process (Inter2a →TS2-3a → Inter3a). In view of the structural parameters, the double unpaired electrons on Inter1a* and Inter2a mainly locate on the C3O group, and thus their C3O bond distances are significantly longer than that in Inter1a (Figure 1). As long as the electron transfers to R1 and R1&R2 groups, the C3O bond is significantly shortened (from 1.287 to 1.236 Å). Meanwhile, the π-bonding of C1C2 bond and C3C4 bonds is broken during the C1−C3 bond formation, and thus the bond lengths continuously increase during the process of Inter2a → TS2-3a → Inter3a (Table 1). 3.2.2. Bielectron Exchange Mechanism. According to bielectron pathway,34 visible light first initiates the excitation of TX1 to its first excited singlet state (S1 state, ΔG = 76.9 kcal/mol), from which intersystem crossing (ISC) to the triplet state (T1) rapidly occurs (Scheme 4a). The relative Gibbs free

Scheme 5. Energy Profiles of Hydrogen Patha

a

transfer pathways (Hydrogen Path B). In Hydrogen Path A, the electron transfer from R1 to TX1* in generating TX1−• and R1+• is endergonic by 22.6 kcal/mol, while the electron transfer from TX1* to R1 is endergonic by 30.1 kcal/mol (Scheme 5). The high energy demands (compared with overall activation barrier of 11.7 kcal/mol of Energy Path A−B) exclude these mechanistic possibilities. By contrast, the direct H atom transfer from R1 to TX1* in Hydrogen Path B is slightly endergonic by 1.5 kcal/mol, and the barrier is 9.5 kcal/mol. Meanwhile, the subsequent cycloaddition on Inter1h requires an energy barrier of 9.8 kcal/mol, and the relative energy of the generated intermediate Inter2h is similar to that of Inter1h. In Scheme 5, the overall energy demand for Hydrogen Path B is 11.5 kcal/mol, and the formation of the first C−C bonded intermediate Inter2h is endergonic by 1.9 kcal/mol. To this end, the kinetic facility of the Hydrogen Path B is comparable to that of the Energy Path A−B (with overall activation barrier of 11.5 vs 11.7 kcal/mol). However, the Hydrogen Path B is thermodynamically reversible (endergonic by 1.9 kcal/mol), while Energy Path A−B is thermodynamically highly feasible (exergonic by 11.6 kcal/mol). Therefore, the possibility of H transfer mechanism is excluded from thermodynamic aspect. 3.2.4. Comparison of Energy-, Bielectron-, and HydrogenTransfer Mechanisms. According to the aforementioned results and discussion, the energy-transfer mechanism is relatively more favorable than the bielectron exchange and Htransfer mechanisms, and Energy Path A−B is the most favorable pathway. The C1−C3 bond formation is the rate- and stereoselectivity determining step for the reaction between R1 and R2, and the overall energy barrier is 11.7 kcal/mol. exo-P1anti is predicted the main product due to the significant lower activation barrier compared with those of the other stereoisomers.65 This conclusion agrees well with the predominant formation of exo-P1-anti with 91% ee in Bach’s experiments.32 3.3. Substituent Effect of Olefins on Stereoselectivity. In the previous experiments, the stereoselectivity of the [2 + 2] cyclization is sensitive to the substituent effect of the olefin substrate. To interpret such observation, we further examined the energetics of the reaction between R1 and vinyl acetate (VA). For clarity, only the rate-determining transition states are shown in Scheme 6, and more details are given in the SI. All species related to VA is named with the suffix of VA.

Scheme 4. (a) Excitation of Photosensitizer TX1 and (b) Electron Exchange Step in Bielectron Patha

a

Energies are given in kcal/mol.

Energies are given in kcal/mol.

energy of triplet state TX1* is 58.9 kcal/mol. Thereafter, two electronic exchange occurs between TX1* and R1 to generate the triplet state R1* (i.e., Inter1b*) and ground state TX1 (Scheme 4b). Thermodynamically, this process is endergonic by 1.1 kcal/mol. However, this process formally requires dissociation of the paired electrons on HOMO of R1 to prepare for the electron donating and accepting process. According to the calculation results, the pre-excitation of R1 requires energy of over 88.9 kcal/mol, indicating that such transformation can hardly occur under the visible-light irradiation. In addition, even if the partial electron (rather than the aforementioned entire electron transfer) could occur, the relative energy of the intermediate Interex in Scheme 4b (ΔG = 67.4 kcal/mol; see the SI for details) is higher than that of Inter1a* (ΔG = 58.7 kcal/mol in Figure 2), and the subsequent cyclization on the formed Inter1b* is kinetically disfavored compared with the Energy Path A−B (Figure 2). Therefore, the Bielectron exchange mechanism is less favorable compared with the energy-transfer mechanism. 3.2.3. H-Transfer Mechanism. In accordance with Ji and coworkers’ recent study,35 the hydrogen-transfer mechanism E


Article


4. CONCLUSIONS The recent reported thioxanthone-mediated [2 + 2] cycloaddition of 2(1H)-quinolones and olefins is a pioneering study on visible-light-mediated, enantioselective intermolecular [2 + 2] cycloaddition. Nonetheless, many mechanistic details (including the possible excitation modes of the novel thioxanthone catalyst, the rate-determining step, and the substituent effect of olefin substrates on the stereoselectivity) remain unsettled. After carefully examining the detailed energy profiles of the target reaction with DFT calculations, we got the following conclusions: (1) During the interaction between photosensitizer (TX1) and substrates, the energy-transfer mechanism (Energy Path A−B) favors the bielectron exchange and H-transfer pathways. The bielectron exchange mechanism is prohibited by the difficulty in pre-excitation of substrate and the associated charge-transfer processes. The H-transfer mechanism is precluded due to the low thermodynamic facility. (2) The energy-transfer mechanism consists of the complexation and excitation of photosensitizer, the first C−C bond formation, the dissociation of sensitizer, triplet to singlet electronic state crossing, and the second C−C bond formation steps. The first C−C bond formation in the cycloaddition process is the rate- and selectivity-determining step. Synergistic energy and electron transfer from TX1 to the substrate moieties take place along the first C−C bond formation process. (3) Regarding the substituent effect of the olefin substrate, the π-accepting substituent favors the ligation of the photosensitizer, so that the steric hindrance induced by the bulky photosensitizer results in high stereoselectivity. By contrast, the π-donating substituent (such as −OAc) results in an inverse electronic effect and favorable dissociation of photosensitizer. Therefore, the stereoselectivity is significantly lowered. Finally, we hope the present study could benefit deep understandings on the enantioselective [2 + 2] cycloaddition and the future development of more powerful photosensitizer available in visible-light irradiation.

Scheme 6. Relative Free Energies of Rate-Determining Transition States and Products in Energy Path A/B-VA and the Other Three Stereoisomeric Pathways

Indeed, as suggested by Bach and coworkers, the origin of the lowered stereoselectivity is caused by the dissociation of the photosensitizer TX1. The calculation results indicate that the TX1 dissociation-first pathway (Energy Path B-VA) is indeed more favorable than the C−C bond formation-first mechanisms (Energy Path A-VA). In detail, the relative energy of TS2-3bVA is lower than that of TS2-3a-VA by 1.2 kcal/mol (Scheme 6a). In line with Energy Path B-VA, the activation barrier for the formation of the different stereoisomers P-exoanti-VA, Pendoanti-VA, P-exosyn-VA, and P-endosyn-VA is 14.4, 20.6, 20.4, and 15.1 kcal/mol, respectively (Scheme 6b). By contrast, the related activation barrier for Energy Path A-VA is 15.6, 26.1, 21.5, and 20.2 kcal/mol, respectively. According to these results, the main product for the VA substrate is P-exoanti-VA, while the low-energy gap between TS2-3b-VA and TS2-3bendosyn-VA indicates that P-endosyn-VA could also be generated as the side product. This conclusion is consistent with the reported experimental results that P-exoanti-VA was generated in 42% yield with 58% ee, while P-endosyn-VA was obtained in 36% yield with 43% ee.32 The good correlation between experiments and calculation results verifies the theoretical methods and the proposed mechanism. Finally, it remains unknown why the catalyst is favorably dissociated before cycloaddition in the presence of the −OAc substituent, while it tends to be retained when −COEt is used. Here is our understanding: −COEt is a π-acceptor (electron flows from double bond to the carbonyl group), whereas −OAc is a π-donor (electron flows from the lone pair on oxygen atom to the double bond). Therefore, the key electronic interaction between the two olefin substrates is essentially different. In −COEt system, the olefin R2 acts as the electron acceptor, and it accepts 0.053 e from the TX1-R1 moiety in the first C−C bond formation process (according to the NBO analysis). By contrast, in the −OAc system, the electron flow from TX1-R1 to VA is prohibited because VA favorably acts as an electron donor. Indeed, in the first C−C formation step, VA donates 0.121 e to the TX1-R1 moiety. In this case, a predissociation of the TX1 could significantly release the electron density on R1 moiety (the NBO charges of R1 group in TS2-3a-VA and TS23b-VA are −0.133 and −0.125, respectively), and thus the C− C bond formation could be achieved with more easiness.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpca.7b02995. Detailed transformation of Energy Paths A-VA and BVA, the effect of different DFT functions, MECP analysis and the Cartesian coordinates, and sum of electronic and thermal free energies in CH3CN solvent for each species. (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Zhimin Dang: 0000-0003-4427-8779 Haizhu Yu: 0000-0003-3010-1331 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This study is supported by NSFC (21672001), outstanding youth financial support in Universities of Anhui Province (J01005182), and the scientific research funds of Anhui F


Article


(20) Du, J.; Skubi, K. L.; Schultz, D. M.; Yoon, T. P. A Dual-Catalysis Approach to Enantioselective [2 + 2] Photocycloadditions Using Visible Light. Science 2014, 344, 392−396. (21) Lewis, F. D.; Barancyk, S. V. Lewis Acid Catalysis of Photochemical Reactions. VIII: Photodimerization and Cross-Cycloaddition of Coumarin. J. Am. Chem. Soc. 1989, 111, 8653−8661. (22) Corey, E. J. Enantioselective Catalysis Based on Cationic Oxazaborolidines. Angew. Chem., Int. Ed. 2009, 48, 2100−2117. (23) Vallavoju, N.; Selvakumar, S.; Jockusch, S.; Sibi, M. P.; Sivaguru, J. Enantioselective Organo-Photocatalysis Mediated by Atropisomeric Thiourea Derivatives. Angew. Chem., Int. Ed. 2014, 53, 5604−5608. (24) Cauble, D. F.; Lynch, V.; Krische, M. J. Studies on the Enantioselective Catalysis of Photochemically Promoted Transformations: “Sensitizing Receptors” as Chiral Catalysts. J. Org. Chem. 2003, 68, 15−21. (25) Tyson, E. L.; Farney, E. P.; Yoon, T. P. Photocatalytic [2 + 2] Cycloadditions of Enones with Cleavable Redox Auxiliaries. Org. Lett. 2012, 14, 1110−1113. (26) Du, J.; Yoon, T. P. Crossed Intermolecular [2 + 2] Cycloadditions of Acyclic Enones via Visible Light Photocatalysis. J. Am. Chem. Soc. 2009, 131, 14604−14605. (27) Ischay, M. A.; Anzovino, M. E.; Du, J.; Yoon, T. P. Efficient Visible Light Photocatalysis of [2 + 2] Enone Cycloadditions. J. Am. Chem. Soc. 2008, 130, 12886−12887. (28) Poplata, S.; Tröster, A.; Zou, Y.-Q.; Bach, T. Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions. Chem. Rev. 2016, 116, 9748−9815. (29) Lu, Z.; Yoon, T. P. Visible Light Photocatalysis of [2 + 2] Styrene Cycloadditions by Energy Transfer. Angew. Chem., Int. Ed. 2012, 51, 10329−10332. (30) Alonso, R.; Bach, T. A Chiral Thioxanthone as an Organocatalyst for Enantioselective [2 + 2] Photocycloaddition Reactions Induced by Visible Light. Angew. Chem., Int. Ed. 2014, 53, 4368−4371. (31) Mayr, F.; Brimioulle, R.; Bach, T. A Chiral Thiourea as a Template for Enantioselective Intramolecular [2 + 2] Photocycloaddition Reactions. J. Org. Chem. 2016, 81, 6965−6971. (32) Tröster, A.; Alonso, R.; Bauer, A.; Bach, T. Enantioselective Intermolecular [2 + 2] Photocycloaddition Reactions of 2(1H)Quinolones Induced by Visible Light Irradiation. J. Am. Chem. Soc. 2016, 138, 7808−7811. (33) Maturi, M. M.; Bach, T. Enantioselective Catalysis of the Intermolecular [2 + 2] Photocycloaddition between 2-Pyridones and Acetylenedicarboxylates. Angew. Chem., Int. Ed. 2014, 53, 7661−7664. (34) Dexter, D. L. A Theory of Sensitized Luminescence in Solids. J. Chem. Phys. 1953, 21, 836−850. (35) Shen, L.; Ji, H.-F. Theoretical Study on Reactions of Triplet Excited State Thioxanthone with Indole. Int. J. Mol. Sci. 2009, 10, 4284−4289. (36) Shen, R.; Corey, E. J. Studies of the Stereochemistry of [2 + 2]Photocycloaddition Reactions of 2-Cyclohexenones with Olefins. Org. Lett. 2007, 9, 1057−1059. (37) Jaque, P.; Toro-Labbe, A.; Geerlings, P.; De Proft, F. Theoretical Study of the Regioselectivity of [2 + 2] Photocycloaddition Reactions of Acrolein with Olefins. J. Phys. Chem. A 2009, 113, 332−344. (38) Weixler, R.; Hehn, J. P.; Bach, T. On the Regioselectivity of the Intramolecular [2 + 2]-Photocycloaddition of Alk-3-enyl Tetronates. J. Org. Chem. 2011, 76, 5924−5935. (39) Brimioulle, R.; Bauer, A.; Bach, T. Enantioselective Lewis Acid Catalysis in Intramolecular [2 + 2] Photocycloaddition Reactions: A Mechanistic Comparison between Representative Coumarin and Enone Substrates. J. Am. Chem. Soc. 2015, 137, 5170−5176. (40) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian 09, revision B01; Gaussian, Inc.: Wallingford, CT, 2010. (41) González-Béjar, M.; Stiriba, S. E.; Domingo, L. R.; Pérez-Prieto, J.; Miranda, M. A. Mechanism of Triplet Photosensitized Diels-Alder Reaction between Indoles and Cyclohexadienes: Theoretical Support for an Adiabatic Pathway. J. Org. Chem. 2006, 71, 6932−6941.

University (J01006021). We thank the National Supercomputing Center in Shenzhen for providing the computational resources and Gaussian09 software.

■

REFERENCES

(1) Yoon, T. P. Visible Light Photocatalysis: The Development of Photocatalytic Radical Ion Cycloadditions. ACS Catal. 2013, 3, 895− 902. (2) Piao, S.-J.; Song, Y.-L.; Jiao, W.-H.; Yang, F.; Liu, X.-F.; Chen, W.S.; Han, B.-N.; Lin, H.-W. Hippolachnin A, A New Antifungal Polyketide from the South China Sea Sponge Hippospongia Lachne. Org. Lett. 2013, 15, 3526−3529. (3) Sinninghe Damsté, J. S.; Strous, M.; Rijpstra, W. I. C.; Hopmans, E. C.; Geenevasen, J. A. J.; van Duin, A. C. T.; van Niftrik, L. A.; Jetten, M. S. M. Linearly Concatenated Cyclobutane Lipids Form a Dense Bacterial Membrane. Nature 2002, 419, 708−712. (4) Aimi, N.; Inaba, M.; Watanabe, M.; Shibata, S. Chemical Studies on the Oriental Plant Drugs-XXIII: Paeoniflorin, A Glucoside of Chinese Paeony Root. Tetrahedron 1969, 25, 1825−1838. (5) Namyslo, J. C.; Kaufmann, D. E. The Application of Cyclobutane Derivatives in Organic Synthesis. Chem. Rev. 2003, 103, 1485−1538. (6) Xu, Y.; Conner, M. L.; Brown, M. K. Cyclobutane and Cyclobutene Synthesis: Catalytic Enantioselective [2 + 2] Cycloadditions. Angew. Chem., Int. Ed. 2015, 54, 11918−11928. (7) Blakemore, D. C.; Bryans, J. S.; Carnell, P.; Carr, C. L.; Chessum, N. E. A.; Field, M. J.; Kinsella, N.; Osborne, S. A.; Warren, A. N.; Williams, S. C. Synthesis and in Vivo Evaluation of Bicyclic Gababutins. Bioorg. Med. Chem. Lett. 2010, 20, 461−464. (8) Trost, B. M. Atom EconomyA Challenge for Organic Synthesis: Homogeneous Catalysis Leads the Way. Angew. Chem., Int. Ed. Engl. 1995, 34, 259−281. (9) Belluš, D.; Ernst, B. Cyclobutanones and Cyclobutenones in Nature and in Synthesis [New Synthetic Methods (71)]. Angew. Chem., Int. Ed. Engl. 1988, 27, 797−827. (10) Brimioulle, R.; Bach, T. Enantioselective Lewis Acid Catalysis of Intramolecular Enone [2 + 2] Photocycloaddition Reactions. Science 2013, 342, 840−843. (11) Ischay, M. A.; Lu, Z.; Yoon, T. P. [2 + 2] Cycloadditions by Oxidative Visible Light Photocatalysis. J. Am. Chem. Soc. 2010, 132, 8572−8574. (12) Mojr, V.; Svobodová, E.; Straková, K.; Neveselý, T.; Chudoba, J.; Dvořaḱ ová, H.; Cibulka, R. Tailoring Flavins for Visible Light Photocatalysis: Organocatalytic [2 + 2] Cycloadditions Mediated by a Flavin Derivative and Visible Light. Chem. Commun. 2015, 51, 12036− 12039. (13) Doi, T.; Kawai, H.; Murayama, K.; Kashida, H.; Asanuma, H. Visible-Light-Triggered Cross-Linking of DNA Duplexes by Reversible [2 + 2] Photocycloaddition of Styrylpyrene. Chem. - Eur. J. 2016, 22, 10533−10538. (14) Clay, A.; Vallavoju, N.; Krishnan, R.; Ugrinov, A.; Sivaguru, J. Metal-Free Visible Light-Mediated Photocatalysis: Controlling Intramolecular [2 + 2] Photocycloaddition of Enones through Axial Chirality. J. Org. Chem. 2016, 81, 7191−7200. (15) Gassner, C.; Hesse, R.; Schmidt, A. W.; Knölker, H. J. Total Synthesis of the Cyclic Monoterpenoid Pyrano [3,2-a] Carbazole Alkaloids Derived from 2-hydroxy-6-methylcarbazole. Org. Biomol. Chem. 2014, 12, 6490−6499. (16) Carreira, E. M.; Fessard, T. C. Four-Membered Ring-Containing Spirocycles: Synthetic Strategies and Opportunities. Chem. Rev. 2014, 114, 8257−8322. (17) Marson, C. M. New and Unusual Scaffolds in Medicinal Chemistry. Chem. Soc. Rev. 2011, 40, 5514−5533. (18) Bach, T.; Hehn, J. P. Photochemical Reactions as Key Steps in Natural Product Synthesis. Angew. Chem., Int. Ed. 2011, 50, 1000− 1045. (19) Hoffmann, N. Photochemical Reactions as Key Steps in Organic Synthesis. Chem. Rev. 2008, 108, 1052−1103. G


Article

The Journal of Physical Chemistry A (42) Zhu, X.-H; Li, W.-P; Yan, H.; Zhong, R.-G. Triplet Phenacylimidazoliums-Catalyzed Photocycloaddition of 1,4-Dihydropyridines: An Experimental and Theoretical Study. J. Photochem. Photobiol., A 2012, 241, 13−20. (43) Kumar, V. R.; Rajkumar, N.; Ariese, F.; Umapathy, S. Direct Observation of Thermal Equilibrium of Excited Triplet States of 9,10Phenanthrenequinone. A Time-Resolved Resonance Raman Study. J. Phys. Chem. A 2015, 119, 10147−10157. (44) Pandey, R.; Umapathy, S. Simultaneous Detection of two triplets: A Time-Resolved Resonance Raman study. J. Phys. Chem. A 2012, 116, 8484−8489. (45) Pandey, R.; Umapathy, S. Time-Resolved Resonance Raman Spectroscopic Studies on the Triplet Excited State of Thioxanthone. J. Phys. Chem. A 2011, 115, 7566−7573. (46) Becke, A. D. Density-Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648−5652. (47) Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785−789. (48) Barone, V.; Cossi, M. Quantum Calculation of Molecular Energies and Energy Gradients in Solution by a Conductor Solvent Model. J. Phys. Chem. A 1998, 102, 1995−2001. (49) Mennucci, B.; Tomasi, J. Continuum Solvation Models: A New Approach to the Problem of Solute’s Charge Distribution and Cavity Boundaries. J. Chem. Phys. 1997, 106, 5151−5158. (50) Fukui, K. The Path of Chemical Reactions-the IRC approach. Acc. Chem. Res. 1981, 14, 363−368. (51) Theory and Applications of Computational Chemistry: The First 40 Years; Dykstra, C. E., Frenking, G., Kim, K. S., Scuseria, G. E., Eds.; Elsevier, 2011. (52) Hratchian, H. P.; Schlegel, H. B. Accurate Reaction Paths Using a Hessian Based Predictor-Corrector Integrator. J. Chem. Phys. 2004, 120, 9918−9924. (53) Hratchian, H. P.; Schlegel, H. B. Using Hessian Updating to Increase the Efficiency of a Hessian Based Predictor-Corrector Reaction Path Following Method. J. Chem. Theory Comput. 2005, 1, 61−69. (54) Saielli, G.; Nicolaou, K. C.; Ortiz, A.; Zhang, H.; Bagno, A. Addressing the Stereochemistry of Complex Organic Molecules by Density Functional Theory-NMR: Vannusal B in Retrospective. J. Am. Chem. Soc. 2011, 133, 6072−6077. (55) Ding, S.-T.; Song, L.-J.; Chung, L. W.; Zhang, X.-H.; Sun, J.-W.; Wu, Y.-D. Ligand-Controlled Remarkable Regio-and Stereodivergence in Intermolecular Hydrosilylation of Internal Alkynes: Experimental and Theoretical Studies. J. Am. Chem. Soc. 2013, 135, 13835−13842. (56) Li, Z.; Fu, Y.; Zhang, S.-L.; Guo, Q.-X.; Liu, L. Heck-Type Reactions of Imine Derivatives: A DFT Study. Chem. - Asian J. 2010, 5, 1475−1486. (57) Noted that the zero-point energies were also examined. Regarding the stereoselectivity, it is found that the relative facilities of different pathways are retained no matter which energy is used for discussion (i.e., Energy Path A−B is the most favourable pathway compared with the other three stereoselective pathways). (58) Zhao, Y.; Truhlar, D. G. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 Other Functionals. Theor. Chem. Acc. 2008, 120, 215−241. (59) Perdew, J. P.; Burke, K.; Ernzerhof, M. D. of Physics and NOL 70118 J. Quantum Theory Group Tulane University. Phys. Rev. Lett. 1996, 77, 3865−3868. (60) Perdew, J. P.; Burke, K.; Ernzerhof, M. Generalized Gradient Approximation Made Simple. Phys. Rev. Lett. 1997, 78, 1396. (61) Harvey, J. N.; Aschi, M.; Schwarz, H.; Koch, W. The Singlet and Triplet States of Phenyl Cation. A Hybrid Approach for Locating Minimum Energy Crossing Points between Non-Interacting Potential Energy Surfaces. Theor. Chem. Acc. 1998, 99, 95−99.

(62) Koga, N.; Morokuma, K. Determination of the Lowest Energy Point on the Crossing Seam between Two Potential Surfaces Using the Energy Gradient. Chem. Phys. Lett. 1985, 119, 371−374. (63) Lundberg, M.; Siegbahn, P. E. M. Minimum Energy Spin Crossings for an O-O Bond Formation Reaction. Chem. Phys. Lett. 2005, 401, 347−351. (64) Stranger, R.; Yates, B. F. Mixing of Electronic States in Molybdenum Complexes Involved in Nitrogen Activation. Chem. Phys. 2006, 324, 202−209. (65) In addition to B3LYP/6-31G* method, the effect of different DFT methods (M05, M06, M11-L, ωB97XD, and B3LYP-D3) was also examined. All of these methods give consistent conclusion (see the SI for more details).

H


Mechanistic Investigation of Visible-Light-Induced Intermolecular [2+ 2

Recommend Documents