Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Mechanism of Iridium-Mediated Selective Arene Cleavage: Insights from Density Functional Theory (DFT) Calculations Xiuling Wen, Xiajun Wu, and Juan Li* Department of Chemistry, Jinan University, Huangpu Road West 601, Guangzhou, Guangdong 510632, People’s Republic of China S Supporting Information *
ABSTRACT: The mechanism and regioselectivity of iridiummediated cleavage of aromatic C−C bonds in a series of monomethylated, dimethylated, and trimethylated benzenes without the activation of weaker C−H and C−C bonds are clarified using density functional theory (DFT) calculations. The calculations explained why the reactivity of the coordinated arene in the observed C−C bond cleavage reaction decreases as the degree of substitution decreases.
T
Scheme 1. Iridium-Mediated Selective Cleavage of Aromatic C−C Bond
he most fundamental organic molecular skeleton consists of C−C bonds. The selective activation of C−C bonds is a topic of increasing interest, because of its powerful and widespread applications in areas, such as the petroleum industry, environmental protection, and pharmaceuticals.1 However, C−C bond cleavage in some hydrocarbon compounds is still a challenge, because of unfavorable kinetics and thermodynamics. The kinetic factors arise from the greater steric hindrance and higher directionality of C−C σ-bond orbitals, compared with those of more exposed C−H bonds. Thermodynamically, M−C (where M is a metal) bonds are weaker than M−H bonds.2 Kinetic and thermodynamic limitations have been overcome by using organometallic complexes to cleave C−C bonds, based on the release of ring-strain energy of highly strained substrates,3 the formation of aromatic systems,4 chelation-assisted cyclometalation,5 βcarbon elimination,6 and co-catalyst use.7 Although significant advances have been made in C−C bond cleavage in aliphatic compounds, cleavage of resonancestabilized C−C bonds in aromatic compounds is still difficult. The cleavage of a benzene ring over solid catalysts usually requires high temperatures and suffers from poor selectivity, as a result of competing activation of the weaker C−C and C−H bonds found in aromatic molecules.8 Several transition-metal complexes have been reported to cleave aromatic C−C bonds under milder conditions, but yields are poor, and prior chemical modification of the arene ring is needed.9 Recently, Sergeev’s group reported an iridium-mediated selective cleavage of aromatic C−C bonds under mild conditions in high yields, without activation of weaker C−C and C−H bonds (see Scheme 1).10 The cleavage is enabled by iridium-induced deformation of the arene ring, which creates temporary ring strain and promotes direct and selective iridium insertion into the inert arene ring C−C bonds. Expansion of this strategy requires a deeper understanding of the catalytic mechanism and insights into the following issues: © XXXX American Chemical Society
(1) Why does the reactivity of the coordinated arene in the observed C−C bond cleavage reaction decrease as the degree of substitution decreases? (2) How is the chemoselectivity controlled in the reactions of xylenes? Therefore, we performed a theoretical study of iridiummediated selective cleavage of aromatic C−C bonds to resolve these issues. We expect this study to inspire future design of catalysts for arene functionalizations through C−C activation (see the Supporting Information (SI) for computational details). In this study, we started our own investigation from the intermediates IN1A, IN1B, and IN1C to the final products 2a, 2b, and 2c, on which we understand the arene cleavage mechanism. Based on the components available in the catalytic system, we examined various possible routes for arene cleavage. First, the insertion of a single iridium metal center into the arene ring in IN1A was calculated, as shown in Scheme 2. The transition state TS1A for iridium insertion, with the Ir−η3phenyl coordination mode, had a high free-energy barrier (i.e., 46.1 kcal/mol). The energy barrier was not consistent with the experimental temperature, i.e., 323 K, reported by Sergeev.10 Received: January 19, 2018
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DOI: 10.1021/acs.orglett.8b00200 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
via transition state TS4A or TS5A, respectively, by spanning a barrier of 25.0 or 6.0 kcal/mol, respectively (Figure 1). The coordinated arenes in the two diiridium complexes IN5A and IN6A were deformed, with a bending angle of 17.9° and 38.5°, respectively. Subsequent C−C cleavage via transition state TS6A or TS7A had an energy barrier of 39.9 or 62.3 kcal/mol, respectively, relative to intermediate IN3A. Therefore, our energetic results ruled out the two diiridium pathways. We then considered the possibility of a tri-iridium pathway (Figure 2). Our calculations showed that the tri-iridium η2:η2:η2
Scheme 2. Arene Cleavage of Mesitylene Assisted by One Iridiuma
a
Free energies are given in kcal/mol.
We then calculated the insertion of one iridium into the arene ring, with the assistance of another iridium. Two η4:η2 complexes IN3A (−30.3 kcal/mol) and IN4A (−19.1 kcal/ mol) could be formed when the second iridium coordinated to the arene ring. The structure in which two iridium centers were on the same side of the arene ring (IN3A) was energetically favored. This higher stability of IN3A, compared with that of IN4A, was the result of weak Ir−Ir bond formation (Ir−Ir = 3.18 Å). The iridium insertion pathway from IN3A via transition state TS2A was shown by a green line in Figure 1; it had a high energy barrier (i.e., 57.2 kcal/mol). The barrier for iridium insertion from the IN4A intermediate was 30.3 kcal/ mol (labeled in blue, Figure 1), which was also too high to be accessible. IN3A can also be transformed to the diiridium η2:η2 complex IN5A (Ir−Ir = 2.51 Å) or η3:η3 complex IN6A (Ir−Ir = 2.88 Å)
Figure 2. Calculated free-energy profiles for tri- and tetra-iridium pathways for mesitylene. Free energies are relative to IN1A and are given in kcal/mol.
complex IN7A was more stable than the di-iridium η3:η3 complex IN6A by 23.9 kcal/mol. The coordinated arene in IN7A was hardly deformed. The lengths of the three Ir−Ir bonds in IN7A were ∼2.78 Å. From IN7A, iridium was inserted into the C−C bond in the arene via transition state TS8A, generating IN8A; this had an energy barrier of 23.3 kcal/mol, relative to the intermediate IN7A. The energy barrier for the tri-iridium pathway was clearly much lower than those for the mono- and di-iridium pathways. The lengths of the three Ir−Ir bond in TS8A were 2.79, 2.80, and 2.73 Å; this indicated that the three Ir−Ir bonds were still present in TS8A. However, one CC in TS8A was not coordinated with iridium, because of C−C bond cleavage. We were intrigued by this observation and, therefore, considered a tetra-iridium pathway. For the tetra-iridium pathway, the η2:η2:η2 complex IN7A was first transformed into the η2:η1:η2:η1 complex IN9A (−56.3
Figure 1. Calculated free-energy profiles for arene cleavage of mesitylene assisted by two iridium catalysts. Free energies are relative to IN1A, and are given in kcal/mol. B
DOI: 10.1021/acs.orglett.8b00200 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters kcal/mol). The coordinated arene in the tetra-iridium complex IN9A was deformed, with a bending angle of 25.4°. The instability of IN9A, compared with IN7A, can be attributed to the weaker Ir−Ir bond. The lengths of the four Ir−Ir bonds in IN9A were 2.82, 2.95, 2.91, and 2.84 Å. The next step, i.e., iridium insertion, occurred via transition state TS9A to give IN10A, with a realizable energy barrier of 15.4 kcal/mol, relative to IN7A. From IN9A to TS9A, two iridium atoms switched from the η2 to the η1 mode. Tetra-iridium-assisted C− C cleavage had the lowest energy barrier among the four pathways discussed above. Therefore, the tetra-iridium pathway enabled strong coordination with the arene in the transition state, and opening of the C−C bond was favored. A second iridium then inserted into the Ir−C bond by spanning a barrier of 12.3 kcal/mol (TS10A), relative to IN10A, generating IN11A. Finally, an iridium approached the CC bond and was converted to IN12A. The Ir1−Ir2 bond length of 2.81 Å in IN12a, which is close to the experimental value (2.74 Å) found in complex 2a,10 should be a IrII−IrII single bond.11 This result can be further supported by the NBO charge analysis. The atomic charges calculated for two Ir atoms in IN12a (0.19 and 0.17) are very close. A concerted process was also possible, in which insertions of two iridium atoms occurred simultaneously. However, the energy of the concerted process was too high to be accessible.12 We now turn to the issue of selective C−C cleavage in xylene (see Figure 3). The likelihood of a tetra-iridium pathway, rather than mono-, di-, and tri-iridium pathways, was assessed by theoretical examination of four pathways for arene C−C bond activation in xylene systems. The tetra-iridium pathway was favored for a xylene substrate (see Figure 3, as well as Figures S1−S4 and Scheme S1 in the SI). Therefore, further consideration of the mono-, di-, and tri-iridium pathways was unnecessary. As shown in Figure 3, cleavage of the C1−C2 bond via TS9B-1y had a barrier of only 17.7 kcal/mol, whereas the barrier for C3−C4 bond cleavage via TS9B-2y was 30.3 kcal/mol, and that for C5−C6 bond activation via TS9B-3y was 29.3 kcal/mol. Therefore, strong regioselectivity toward cleavage of the desired C1−C2 bond was observed, which was consistent with the experimental observations that only the least sterically hindered C1−C2 bond was cleaved.10 Steric effects were critical in achieving the high reactivity of the desired arene C−C bond activation. Next, we attempted to expand the substrate scope computationally, to further explain why the reactivity of the coordinated arene in the observed C−C bond cleavage reaction decreases as the degree of substitution decreases. Two substrates were considered, namely, toluene and benzene. The tetra-iridium pathway was still found to have the lowest reaction barrier for the arene C−C activation step for both substrates.13 Our calculations showed that the energy barriers for iridium insertion into toluene and benzene were 27.8 and 30.2 kcal/ mol, respectively (see Scheme 3). The order of the overall computed energy barriers for the four substrates was mesitylene (15.4 kcal/mol) < m-xylene (17.7 kcal/mol) < toluene (27.8 kcal/mol) < benzene (30.2 kcal/mol); this was consistent with order of the experimentally observed reactivities.10 The above argument, which is based on steric factors, nicely explains the regioselectivity for the m-xylene substrate. However, when we consider the trend in the calculated barriers for the insertion reactions of iridium into four arene substrates, it becomes problematic if we do not invoke electronic factors. The structures of the transition states TS9A, TS9B, TS9C, and
Figure 3. Calculated free-energy profiles for tetra-iridium pathways for m-xylene. Solvent-corrected free energies are relative to IN1B and are given in kcal/mol.
Scheme 3. Calculated Free-Energy Profiles for Tetra-iridium Pathways for Toluene and Benzenea
a
Free energies are relative to IN1C or IN1D and are given in kcal/ mol.
TS9D show that the four iridium catalysts and methyl substituents lie above and below the plane of the aromatic C
DOI: 10.1021/acs.orglett.8b00200 Org. Lett. XXXX, XXX, XXX−XXX
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molecule, respectively. This suggests that the steric factor has a slight effect, and electronic factors govern the relative barriers among different substrates. The electron-donating methyl substituent makes the aromatic ring more electron-rich and more nucleophilic. Therefore, the most highly substituted substrate, i.e., mesitylene, has the lowest energy barrier among the four substrates. In summary, we performed a DFT study to clarify the catalytic mechanism and regioselectivity of the system. The free-energy profiles for several possible reaction pathways, namely mono-, di-, tri-, and tetra-iridium pathways, were calculated and compared. The results of these calculations show that the tetra-iridium pathway, in which iridium insertion occurs in a stepwise manner, has the lowest energy. Analysis based on m-xylene as the substrate shows that steric hindrance plays a key role in determining the regioselectivity. Electronic factors nicely explain the observation that benzene gives the highest barrier, and mesitylene gives the lowest barrier.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00200. Computational details, additional computational results, and calculated imaginary frequencies of all transitionstate species (PDF) Tables of Cartesian coordinates and electronic energies for all calculated structures (XYZ)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] ORCID
Juan Li: 0000-0003-0693-3162 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (Grant No. 21573095), the Science and Technology Program of Guangzhou (Grant No. 201707010269), and the High-Performance Computing Platform of Jinan University.
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REFERENCES
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DOI: 10.1021/acs.orglett.8b00200 Org. Lett. XXXX, XXX, XXX−XXX
