A Theoretical Study on the Mechanism of the Oxidative Deborylation/C-C Coupling Reaction of Borepin Derivatives

Article abstract of DOI:10.1021/acs.joc.8b02917

One-electron oxidation of borepin derivatives that consists of a boron-containing seven-membered ring has been reported to cause deborylation/C-C coupling, yielding aromatic compounds. The reaction can be achieved not only by transition metal compounds but also by oxidants without transition metal such as O₂ and other organic compounds. Despite numerous experimental attempts, the mechanism of this peculiar reaction as well as the fate of the BCl part eliminated from borepin remain unclear to date. Based on theoretical approaches using the artificial force induced reaction method, here we address the mechanism of the unusual boron-mediated C-C coupling. For this purpose, two borepin derivatives (1 and 35), bearing ethyl and phenyl groups, respectively, were used as reactants, and FeCl₃/MeNO₂ and O₂ were chosen as oxidants. The calculations revealed reaction pathways that provided an overall picture of the mechanism of the target reaction, which features four key steps, namely, (i) quaternization of the boron atom by the coordination of oxidant, (ii) intersystem crossing, (iii) skeletal rearrangement to form a six-membered ring, and (iv) elimination of a boron moiety. The intrinsic nature of boron, i.e., a strong tendency to accept a coordination ligand even under oxidative conditions, is responsible for the oxidative deborylation/C-C coupling of borepin.

Full text of DOI:10.1021/acs.joc.8b02917

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Article
A Theoretical Study on the Mechanism of the Oxidative
Deborylation/C–C Coupling Reaction of Borepin Derivatives
Cihan Ozen, Yoshiaki Shoji, Takanori Fukushima, and Satoshi Maeda
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02917 • Publication Date (Web): 24 Jan 2019
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A Theoretical Study on the Mechanism of the Oxidative
Deborylation/C–C Coupling Reaction of Borepin Derivatives
Cihan Özen,† Yoshiaki Shoji,‡ Takanori Fukushima,‡ Satoshi Maeda†,§,‖,
*
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† Department of Chemistry, Hokkaido University, Sapporo 060-8510, Japan
‡ Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology,
Yokohama 226-8503, Japan
§Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo 001-
0021, Japan
‖Research and Services Division of Materials Data and Integrated System (MaDIS), National Institute for Materi-
als Science (NIMS), Tsukuba 305-0044, Japan
ABSTRACT: One-electron oxidation of borepin derivatives that consists of a boron-containing seven-membered
ring has been reported to cause deborylation/C–C coupling, yielding aromatic compounds. The reaction can be
achieved not only by transition metal compounds but also by oxidants without transition metal such as O2 and other
organic compounds. Despite numerous experimental attempts, the mechanism of this peculiar reaction as well as
the fate of the BCl part eliminated from borepin remain unclear to date. Based on theoretical approaches using the
artificial force induced reaction method, here we address the mechanism of the unusual boron-mediated C–C cou-
pling. For this purpose, two borepin derivatives (1 and 35), bearing ethyl and phenyl groups, respectively, were
used as reactants, and FeCl3/MeNO2 and O2 were chosen as oxidants. The calculations revealed reaction pathways
that provided an overall picture of the mechanism of the target reaction, which features four key steps, namely, (i)
quaternization of the boron atom by the coordination of oxidant, (ii) intersystem crossing, (iii) skeletal rearrange-
ment to form a six-membered ring, and (iv) elimination of a boron moiety. The intrinsic nature of boron, i.e., a
strong tendency to accept a coordination ligand even under oxidative conditions, is responsible for the oxidative
deborylation/C–C coupling of borepin.
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INTRODUCTION
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The formation of C–C bond is not only the most fundamental issue in organic chemistry but also an important task
in all branches of chemistry. Besides well-established transition metal-catalyzed cross-coupling reactions,1 increas-
ing attention has been paid to new reaction protocols mediated by main-group elements.2 In this context, many
organoboron species are known to mediate C–C coupling,3 which makes use of low electronegativity and high
Lewis acidity of boron. Examples include direct (i.e., non-catalyzed) 1,1- and 1,2-carboboration reactions of al-
kynes,4,5,6 which involve the simultaneous formation of C–C and C–B bonds, allow for regio- and stereoselective
synthesis of substituted alkenes.
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Recently, we reported that highly efficient direct 1,2-carboboration between various alkynes and 9-borafluorene
derivatives takes place to give the corresponding borepin derivatives featuring a boron-containing seven-membered
ring (Figure 1).7 Unexpectedly, the resulting borepin derivatives, upon exposed to ambient air, underwent deboryla-
tion/C–C coupling to afford phenanthrene derivatives. We later discovered that this deborylation/C–C coupling
reaction of borepin can be achieved efficiently using various oxidizing reagents such as O2, FeCl3, MnO2, AZADO
(2-azaadamantane-N-oxyl), and even using electrochemical oxidation (Figure 1).7a Thus, the direct 1,2-carbobora-
tion of alkynes with 9-borafluorene derivatives, and the subsequent deborylation/C–C coupling of the resulting
borepins offers an efficient synthetic protocol for various types of extended π-systems.7a,b,d
Figure 1. 9-Borafluorene-mediated benzannulation of alkynes featuring sequential 1,2-carboboration and the sub-
sequent oxidative deborylation of the resulting borepin derivatives.7a X = Cl, Br, or OTf; R = various aryl and/or
alkyl groups.
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Along with the synthetic utility, the deborylation/C–C coupling of borepins is quite interesting from a fundamental
mechanistic viewpoint, because borepin, which is intrinsically Lewis acid and hence highly electron deficient, un-
dergoes oxidation to causes intramolecular C–C bond formation. Furthermore, the fate of the BCl part which dis-
sociates from borepin upon its one-electron oxidation still is unclear. We have been curious about how the oxidative
deborylation/C–C coupling of borepin proceeds under very mild conditions (below room temperature) with a high
efficiency. It is expected that either solvent molecules or a certain anionic species derived from the oxidant used
might contribute to promote the elimination of unidentified boron species.
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In this study, we aimed to elucidate the mechanism of the oxidative deborylation/C–C coupling of borepin and to
reveal the nature of the boron-product based on the artificial force induced reaction (AFIR)8 method. For this pur-
pose, we focused on two borepin molecules (1 and 35) as the reactants, both of which were confirmed experimen-
tally to undergo efficient oxidative deborylation/C–C coupling. To reduce the computational costs, compound 1
(Figure 2a) with relatively small ethyl groups was examined for the reaction with FeCl3. Compound 35 with phenyl
groups was used for the reaction with O2.
RESULTS AND DISCUSSION
Structural Calculations of Reactants. First, the conformer search for borepin 1 afforded four different conformers,
as expressed by anti1, anti2, syn1, and syn2 (Figure 2b), which were defined with respect to the ethyl groups. Ener-
getically, syn1 (Figure 3a) has the lowest energy compared to other conformers. The conformers anti1 and anti2 are
slightly higher in energy by 0.9 and 0.3 kcal/mol than syn1, respectively. On the other hand, syn2 lies in the highest
energy state (2.8 kcal/mol). The geometry optimization of FeCl3 (3) was carried out for its doublet, quartet, and
sextet states. According to the calculations, the sextet state has the lowest energy, as expected. Experimentally,
FeCl3 is dissolved in MeNO2 (4), and therefore the possible complexation between FeCl3 and MeNO2 was evaluated.
The calculations indicated that the sextet FeCl3•MeNO2 (65) complex structure (Figure 3b) is slightly favorable
over their non-complexed forms by 1.4 kcal/mol (Figure 4). Also, 65 is more favorable (22.0 kcal/mol) than 45. The
different complex structures such as N- and chelating-coordination modes have been evaluated for the
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FeCl3•MeNO2, though none of them could be located. All trials turned into structure 65. Additionally, the complex
with the double 4, i.e., FeCl3•(MeNO2)2, has been also optimized, and energetically it is unfavorable by 2.1 kcal/mol
over 65. Although the dimerization is seemed to take place, the existence of 4 hinders it. The calculations showed
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that the 5 is more favorable than that of the dimer FeCl3 by 5.7 kcal/mol. Hence, the combination of 1_syn1 and
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complex 65 was used as a reference point for the whole energy profile in Schemes 1-4 and 6.
Figure 2. (a) Reaction of borepin 1 with FeCl3 (1 equiv.) in DCE/MeNO2 at 25 °C affording 9,10-diethylphenan-
threne 2. (b) Four conformers of 1 (syn1, syn1, anti1, and anti2) derived from a conformational search.
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Figure 3. Optimized geometries of (a) the syn1 conformer of borepin 1 and (b) sextet FeCl3•MeNO2 5. Carbon,
boron, oxygen, nitrogen, chlorine, and iron are depicted in gray, yellow, red, blue, green, and purple, respectively.
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Figure 4. An equilibrium between FeCl3 (3) + MeNO2 (4) and FeCl3•MeNO2 (5).
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Calculations of the Oxidative Deborylation/C–C Coupling of 1 with FeCl3 (3). We carried out multicomponent
AFIR (MC-AFIR) calculations with anti1 and 3 to obtain approximate equilibrium structures and transition states.
Although sextet is the most favorable state for FeCl3, the quartet and doublet states were also employed in MC-
AFIR calculations. The results showed that the energies of equilibrium structures of the doublet are higher than
those of the sextet and quartet states. Hence, we did not take the doublet state into consideration in further path
refinement (RePATH) calculation.
As shown in Scheme 1, the reaction is initiated by the interaction between 1 and 3, resulting in B–Cl bond associ-
ation in transition state 6, from which intermediate 7 is formed via tetrahedralization (i.e., quaternization) of boron.
Because the sextet and quartet states are viable in the course of the reaction, it is needed to consider the intersystem
crossing reaction from the sextet to the quartet for 7. Among 7 with different geometries in the borepin moiety, that
involving anti2 (denoted as 7_anti2 hereafter) requires the lowest energy for the intersystem crossing reaction from
sextet 7 (67) to quartet 7 (47). Intermediate 7 with a quaternized boron atom has a structure favorable for a skeletal
rearrangement into intermediate 9 with a six-membered-ring through transition state 8. At the final stage, the boron
moiety of 9 is eliminated via transition state 10, resulting in product 2 and FeCl2(BCl2) (11). Although the sextet
and quartet states of the chemical species involving in Scheme 1 show geometrical similarity, they have remarkable
differences in free energy. For example, the energies of the sextet state of 6 (66) are lower than those of its quartet
state (46). In contrast, mostly 68 and 610 lie in an energy state higher than those of the corresponding species in the
quartet state (Supporting Information, Scheme S1). Additionally, the free energy of 411 is lower than that of 611.
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Scheme 1. The reaction mechanism between 1 and 3 initiated by a B-Cl bonding.
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Calculations of the Oxidative Deborylation/C–C Coupling of 1 with FeCl3•MeNO2 (5). The same AFIR proce-
dure (vide supra) was applied to the system with 1 and 65. Scheme 2 illustrates the resultant structures and energies
of each step. The overall mechanisms of the reactions with FeCl3 and FeCl3•MeNO2 show common features such
as the occurrence of a quaternization of boron. However, there are dramatic differences in the product distribution
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step. The reaction starts with the interaction between 1 and 5 to form transition state 12. Then, a Cl atom of 5
makes a bond with boron to give intermediate 13 with a negatively charged four-coordinate boron atom. This pro-
cess is similar to the case of the reaction with FeCl3. In intermediate 13, an intersystem crossing reaction can take
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place before transforming into transition state 14, as the energy value (14.2 kcal/mol) of 14 with anti1 is slightly
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lower than that of 14_syn2 (15.0 kcal/mol). According to the calculations, an energy value of 11.7 kcal/mol is
required for syn1 to cause the intersystem crossing reaction from 613_syn1 to 413_anti2. Following a quaternization
of boron in 13, a ring contraction takes place in intermediate 15 through 14. In the reaction process from 15, the
mechanism differentiates and diverges into two pathways (Pathway A and B). Pathway A includes the dissociation
of the boron moiety from 15 through the interaction between B and Fe atoms to generate transition state 16, and
consequently, a phenanthrene product 2 and a FeCl2(BCl2)•MeNO2 species (17) form. In Pathway B that generates
transition state 18 from 15, the O atom of MeNO2 starts to make bonds to B and Fe atoms, while a B-C bond
cleavage and a Fe-O bond formation occur. The deborylation from 18 gives rise to phenanthrene product 2, along
with a nitroso product 19 and a FeCl2(OBCl2) (20). Taking a closer look at the reaction pathways in terms of energy,
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the sextet and quartet states of 14 with anti1, anti2, and syn1 are comparable to each other, while in 14 with syn2, the
energy of 614_syn2 is lower than that of 414_syn2 (Supporting Information, Scheme S2). For 16, the quartet states
have a lower energy compared to the sextet states, especially for 416_anti1. When compared the two possible path-
ways based on the values of energy, Pathway A involving 16 should be more favorable than Pathway B involving
18 for both quartet and sextet states. The lowest energy (7.4 kcal/mol) is found for 418_syn1. Pathway B that gives
19 and 20 is more exergonic than Pathway A accompanying the formation of a high-energy species of 17. In par-
ticular, this tendency is seen in the sextet-state reaction.
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Scheme 2. The reaction mechanism between 1 and 5 initiated by a B-Cl bonding.
The above results and discussion have featured the reaction pathways initiated by the formation of a B–Cl bond
between 1 and FeCl3. However, in the oxidation of 1 with FeCl3 in the presence of MeNO2, it is also likely that the
reaction is initiated by a B–O bond formation between 1 and FeCl3•MeNO2 (5). Scheme 3 illustrates the whole of
the reaction steps that occur through the formation of intermediate 22 with a quaternized B atom bonding to O atom
from FeCl3•MeNO2. There are two possible transition states (21 and 30) to form 22. However, since transition state
30, in which an interaction between Fe and Cl atoms occurs, is energetically higher than 21 in terms of every
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conformation and multiplicity. Hence, it seems reasonable to consider that the reaction exclusively proceeds
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through transition state 21.
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Notably, the possible pathways are divided in the reactions followed by transition state 23,9 depending on the con-
formation and multiplicity. When 23 bearing syn1 adopts a quartet state, intermediate 27 featuring a B–O–N–O
four-membered (dioxazaboretidine) ring structure results. Subsequently, intermediate 27 undergoes an intersystem
crossing reaction via 28. Although the geometries of 27 and 28 are almost identical, their reactivities are completely
different. For example, while the B-C distance is distance is 1.73 Å in 27, it is 1.74 Å in 28 and then 28 releases
the dioxazaboretidine moiety (29)10 to produce phenanthrene 2. In other cases, a skeletal rearrangement of 22 into
intermediate 24 with a six-membered-ring and a B–O bond is favored. Then, the boron moiety of 24 is eliminated
via transition state 25 to produce 2, FeCl3 (3), oxoborane O=BCl (26), and nitrosomethane (19). Since this final
state is accompanied by the formation of sextet FeCl3, we consider that the transformation from 24 to the products
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occurs at the sextet state. In fact, the geometry optimization of 25 for each conformer was successful, while no
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transition state could be located for 25. Therefore, before going to transition state 25, 424 may undergo an inter-
system crossing reaction into 624.
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Scheme 3. The reaction mechanism between 1 and 5 initiated by a B-O bonding.
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Proposed Mechanisms for the Oxidative Deborylation/C–C Coupling of 1 with FeCl3. Based on all the results
described above, we render the most favorable reaction pathway as illustrated in Scheme 4. The reaction is initiated
with the formation of a B–Cl bond between FeCl3 (63) and 1 adopting a syn1 conformation to give intermediate
67_anti2 and MeNO2 (4), where the activation energy was calculated to be 7.1 kcal/mol. Then, the facile intersystem
crossing reaction from 67_anti2 to 47_anti2 takes place with a very small activation energy (0.3 kcal/mol). The next
step is a largely exergonic process through transition state 48_anti1, which is accompanied by a skeletal rearrange-
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ment from seven-to-six-membered ring, to afford intermediate 9_syn1. At a closer inspection of the molecular
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geometry of 8_anti1 (Figure 5a), the interatomic distance of carbons (1.90 Å) that will be embedded in the six-
membered ring of 49_syn1 is close enough to make a C–C bond. The boron moiety of 49_syn1 is eliminated through
transition state 410_anti2 (Figure 5b) with an activation energy of 18.4 kcal/mol to produce phenanthrene 2, together
with FeCl2(BCl2) (411) and MeNO2 (4). Instead of 410_anti2, the reaction pathway through transition state 418_syn1
is also considered possible, since the energy difference between 418_syn1 and 410_anti2 is only 1.3 kcal/mol. When
the reaction occurs via 418_syn1, FeCl2(OBCl2) (420) is directly formed and then an intersystem crossing takes place
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from quartet to sextet for the structure 20. On the other hand, when the reaction occurs via 10_anti2, 411 is once
formed, but it subsequently transforms into the 420 by the reaction with the MeNO2 (4) and then the intersystem
crossing (420→620) takes place due to the thermodynamic stability of 620 (Scheme 2). The mechanism of the trans-
formation from the 411 to 620 is depicted in Scheme S4 (Supporting Information Section B).
Scheme 4. The most favorable pathway for the oxidative deborylation/C–C coupling by FeCl3 constructed
based on the results of Schemes 1–3.
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Figure 5. Optimized geometries of transition states (a) 48_anti1 and (b) 410_anti2. Carbon, boron, chlorine, and iron
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are depicted in gray, yellow, green, and purple, respectively.
Mechanism of the Oxidative Deborylation/C–C Coupling of 1 with O2. As reported previously, a phenyl-group
substituted borepin (35), when exposed to O2, yields a phenanthrene product 36 (Figure 6). To gain insight into the
mechanism of this reaction, we also carried out the calculation on the reaction of 35 with triplet O2 (337). The
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computational results are illustrated in Scheme 5. The reaction starts with the B–O bond formation between 35 and
337 that leads to the quaternization of boron, giving rise to intermediate 339 via transition state 338 with activation
energy of 22.9 kcal/mol. Although a transition state with a singlet open-shell character (138) possibly occurs in this
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reaction, this structure is energetically unfavorable by 6.4 kcal/mol compared to 38. Thus, we did not include
reactions arising from 138 in the calculation.
Figure 6. Reaction of borepin 35 with O2(g) in DCE at 25 °C affording 9,10-dipheyllphenanthrene 36.
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The reaction sequences from 39 are divided into two pathways. First, a skeletal rearrangement into 41 through
transition state 340 (Figure 7a). Later, an intersystem crossing occurs from 341 via minimum energy seam of cross-
ing (MESX) 42, which lies in a 1.3 kcal/mol lower energy state compared to 341. During the intersystem crossing
reaction, the terminal O atom of the B–O–O moiety simultaneously makes a bond with the anionic carbon, resulting
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in 43. The transformation from 41 to 43 is extremely exergonic (53.5 kcal/mol). The elimination of the boron
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moiety of 43 through transition state 44 affords 36, together with 3-chloro-1,2,3-dioxaborirane (45), where the
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activation energy was calculated to be 21.1 kcal/mol. Second, an intersystem crossing from 39 to 39 through
MESX 46 and its energy is slightly lower (1.2 kcal/mol) than those of 339 and 139 which gives rise to an equilibrium
between them. Products 36 and 45 are directly formed via transition state 147 (Figure 7b) with activation energy of
5.5 kcal/mol. Although transition states 147 and 340 have close similarities in geometry and energy (Figure 7), they
lead to different reaction pathways. Obviously, the difference in reactivity originates from the multiplicity of the
transition states.
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Figure 7. Optimized geometries of transition states (a) 340 and (b) 147. Carbon, boron, oxygen, chlorine, and iron
are depicted in gray, yellow, red, green, and purple, respectively.
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Scheme 5. The reaction mechanism between 1 and 337.
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Calculation of the Deborylation/C–C Coupling of 1 without Oxidant. As a reference, we performed calculations
on a model reaction of 1 with MeNO2 (4) in the absence of oxidant. In this section, we used only the anti1 conformer
of borepin 1, and the result is shown in Scheme 6. The coordination of the O atoms of MeNO2 (4) to the B and C
atoms of 1 triggers the reaction to give rise to intermediate 50 through transition state 48 (Figure 8), where a ring
contraction occurs and the distance between two carbon atoms bonded to the B atom is reduced to 1.87 Å. Transition
state 48 lies in a very high energy state (39.7 kcal/mol). Alternatively, another transition state 49, which is devoid
of interaction with MeNO2, was generated computationally. Since the energy of 49 (47.3 kcal/mol) is much higher
than that of 48, the participation of this transition state is unlikely. In contrast to the aforementioned mechanisms
of the reactions with oxidants, the quaternization of boron and the formation of six-membered ring occur simulta-
neously in a concerted manner through 48. In the next step, the intermediate 50 undergoes disproportionation via
transition state 51 (Figure 8) into three species including phenanthrene 2, nitrosomethane 19, and O=BCl (26). The
computational result is consistent with the experimental result that no reaction of 1 takes place in MeNO2. Obvi-
ously, the first step that yields intermediate 50 through transition state 48 is a strongly energy demanding process
and thus difficult to occur. As clearly shown in Schemes 4 and 5, the presence of oxidants, particularly FeCl3,
significantly reduces the activation energy of the first step due to their coordination ability to the boron center of 1.
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Figure 8. Optimized geometries of transition states (a) 48 and (b) 51. Carbon, boron, oxygen, chlorine, and iron
are depicted in gray, yellow, red, green, and purple, respectively.
Scheme 6. The reaction mechanism between 1 and 4.
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CONCLUSIONS
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We have theoretically studied the mechanism of the oxidative deborylation/C–C coupling of borepin. The obtained
schemes render four key steps; quaternization of the boron atom by the coordination of oxidant, the intersystem
crossing reaction, the skeletal rearrangement to form a six-membered ring, and elimination of a boron moiety.
Through the investigation, we proposed a plausible mechanism of the oxidative deborylation/C–C coupling of 1
with FeCl3•MeNO2 (Scheme 4), which completely reflects the actual reaction conditions. We found that the change
of the multiplicity from sextet to quartet in the first intermediate occurs with small activation energy, and the quartet
state of reaction system is inherited in each species generated in the sequential steps until the formation of phenan-
threne. In this context, it has been reported that the quartet state lies in a lower energy state than the sextet state in
a certain reaction system with FeCl3 as a catalyst.11 Following the generation of phenanthrene, the eliminated boron-
iron complexes further exhibit complicated reactions, which involve the change in the multiplicity of iron from
quartet to sextet. Therefore, there are interconversion processes between the sextet and quartet states in the whole
of the reaction scheme. As for the reaction with O2, the biradical character of the system emerged. The two possible
reaction pathways were calculated, where either triplet (340) or singlet (147) transition state appeared. The energy
of 340 and 147 were almost identical to each other, it was difficult to distinguish which transition state provides a
more favorable pathway. When compared the most energetically demanding processes for both the oxidation reac-
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tions using FeCl3 (49 → 10) and O2 (35 → 38), the former reaction can proceed with 18.4 kcal/mol, while the
latter requires 22.9 kcal/mol. This difference may be reflected in the reaction rates observed experimentally.7a Be-
sides, we also confirmed that the reaction of 1 and MeNO2 without oxidant is not feasible in terms of the energy
profile (Scheme 6).
The computational studies showed that the intrinsic nature of boron, i.e., a strong tendency to accept a coordination
ligand even under oxidative conditions, leads to the quaternization of boron atom to cause the seemingly unusual
oxidative deborylation/C–C coupling of borepin. The formation of the coordinatively saturated boron center results
in the significant reduction of the activation energy associated with a skeletal rearrangement with C–C coupling.
The mechanistic aspects revealed by this study may be useful for comprehensive understanding of boron-mediated
C–C coupling reactions beyond the present reaction system.
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COMPUTATIONAL METHODS
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GRRM program8 combined with Gaussian 0912 has been employed to study the reaction mechanism at 1 atm and
298.15 K. UB3LYP has been chosen as functional.13 6-31G* has been utilized for C, H, N, O, B, and Cl atoms as
basis set. LANL2DZ effective core potential has been utilized for Fe atom.14 To take into account the dispersion
force, Grimme 3 type empirical dispersion correction has been specified.15 Solvent effect has been considered by
single point calculation of optimized geometries using SMD (solvation model based on density)16 solvation method
with 1,2-dichloroethane (DCE) as a solvent. The free energy correction term for vibrational, rotational, and trans-
lational motions is obtained in the gas phase. In single point solvent calculations, Integral=Ultrafine keyword has
been specified to obtain more accurate results. The intersystem crossing reactions have also been considered for
the transition between states where minimum energy seam of crossing (MESX) geometries have been optimized as
critical points of intersystem crossing reactions with OptX keyword of the GRRM program.17 To address the solvent
effect in the intersystem crossing reactions, the average value of the single point energies of the relevant states of
the MESX geometries has been calculated. The model collision energy parameter γ value has been specified as 200
kJ/mol in multicomponent AFIR (MC-AFIR) calculations.18 In this study, firstly MC-AFIR method has been ap-
plied to the reactants and then the acquired results have been refined with RePATH calculation, where in the Re-
PATH calculation LUP (Locally updated planes) path optimization method is applied to the previously obtained
paths by MC-AFIR calculation to find equilibrium and transition state structures.8 After obtaining initial steps, the
further calculations has been carried out with standard optimization methods for the intermediates, products, and
transition states. The intrinsic reaction coordinate (IRC) calculation has been performed automatically by GRRM
program for the transition states to connect them with equilibrium structures.19 All the energy values discussed in
this study are relative Gibbs free energy with single point solvent calculations and in the unit of kcal/mol unless
otherwise stated. It is also noted that all the structures discussed below are local minima or first-order saddle points
optimized on the potential energy surface (without the influence of the artificial force) at the aforementioned com-
putational level, where the number of imaginary frequency modes at each optimized structure are checked by nor-
mal mode analysis. All the distances discussed in this study are in the unit of Angstrom (Å). In the schemes and
figures, H atoms are omitted for clarity. In the Schemes 1-3, the energy values represent energetically the most
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favorable conformation and for each multiplicity. The energy values related with other conformations have been
depicted in Supporting Information Section A Schemes S1-3
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ASSOCIATED CONTENT
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Supporting Information
Cartesian coordinates of the structures and their thermodynamic data (PDF).
AUTHOR INFORMATION
Corresponding Author
* Satoshi Maeda. smaeda@eis.hokudai.ac.jp.
Notes
The authors declare no competing financial interest.
ORCID
Cihan Özen: 0000-0002-2194-9077
Yoshiaki Shoji: 0000-0001-8437-1965
Takanori Fukushima: 0000-0001-5586-9238
Satoshi Maeda: 0000-0001-8822-1147
ACKNOWLEDGMENTS
This work was supported by a grant from the Japan Science and Technology Agency with a Core Research for
Evolutional Science and Technology (CREST) grant in the area of ‘Establishment of Molecular Technology
towards the Creation of New Functions’ at Hokkaido University (Grant No. JPMJCR14L5) and the Cooperative
Research Program of “Network Joint Research Center for Materials and Devices” from MEXT, Japan. T.F.
acknowledges a Grant-in-Aid for Scientific Research on Innovative Areas “π-Figuration: Control of Electron and
Structural Dynamism for Innovative Functions“ (26102008). Y.S. acknowledges KAKENHI (17H03020) from
Japan Society for the Promotion of Science.
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(18) Maeda, S.; Morokuma, K. Finding reaction pathways of type A + B → X: toward systematic prediction of reaction
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