A Mechanistic Insight into the Ligand-Controlled Asymmetric Arylation

Article pubs.acs.org/IC

A Mechanistic Insight into the Ligand-Controlled Asymmetric Arylation of Aliphatic α‑Amino Anion Equivalents: Origin of Regioand Enantioselectivities Qiong Wang, Fang Huang,* Langhuan Jiang, Chuanzhi Sun, Jianbiao Liu, and Dezhan Chen* College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China S Supporting Information *

ABSTRACT: The reaction mechanism and the origins of regio- and enantioselectivities for Pd-catalyzed asymmetric arylation of aliphatic α-amino anion equivalents were investigated computationally. The results indicate that the reaction proceeds via mainly six sequential steps: deprotonation at α′-site of imine, coordination of α-amino anion to Pdcatalyst, oxidative addition, transmetalation, reductive elimination, as well as the final dissociation to release the product and regenerate the catalyst. The transmetalation is a key step on which both enantioselectivity and regioselectivity depend. The charge inversions of α- and α′-C atoms and the orbital interaction between Pd center and α-C in transmetalation step are responsible for the regioselectivity. Additionally, the intermediates before the dissociation step are critical in controlling the enantioselectivity. Noncovalent interactions analyses indicate that the enantioselectivity primarily arises from the CH···π interactions of isopropyl (iPr) groups with the fluorene and the benzene rings for PdL1-catalyzed reaction. benzylamines was reported by Stephen L. Buchwald’s group34 in 2014 using chiral Pd catalysts (see Scheme 1). Several chiral phosphorus ligands that controlled the enantioselectivity were surveyed in their experiment. Later, Jason J. Chruma and coworkers35 took advantage of the asymmetric allylic alkylation of α-imino anions (2-azaallyl anions) to afford enantioenriched homoallylic imines. Very recently, Dawen Niu’s group36 developed a new paradigm for 1,4-disubstituted homoallylic amines’ asymmetric synthesis, in which imines served as nucleophiles via the intermediacy of 2-azaallyl anions. Most of the reactions mentioned there were realized through sophisticated design of chiral catalysts or ligands. However, the detailed reaction mechanism, especially how the regio- and enantioselectivities are controlled by the catalysts and ligands, is still unclear. Herein we report a detailed mechanism study based on the system explored by Stephen L. Buchwald (Scheme 1) on the basis of the density functional theory (DFT). The present results provide a deep understanding of ligandcontrolled asymmetric arylation reaction from views of both electronic effect and noncovalent interactions.

1. INTRODUCTION Chiral amines are key constituents of pharmaceuticals, agrochemicals, and materials,1−4 which are commonly found as intermediates in modern organic synthesis.5−10 Owing to the chiral specificity, developing efficient synthetic procedures to achieve the chiral functionalization of amines,11−13 especially in precise control the asymmetric synthesis of amines bearing an α-stereocenter, is of high importance. Traditionally, enantiomerically pure amines were prepared by resolution of racemic amines with enantiomerically pure chiral acids.13 Recent years, asymmetric reduction of imines14−22 catalyzed by the transition metal complexes is extensively explored, particularly in production of enantiomerically enriched drugs. These methods of chiral amine synthesis, such as nucleophilic carbon-moiety attack to CN double bonds23−28 and catalytic reduction hydrogenation of unsaturated imine electrophiles,29−31 show several advantages over traditional methods in respects of reaction conditions and functional group tolerance. Last several years, using umpolung α-amino anions as nucleophile32,33 to make amines arises to be an important process. The developments of umpolung functionalization of imines via the intermediacy of 2-azaallyl anions provide a new paradigm for the straightforward formation of C−C bond, thereby establishing new approaches for the synthesis of amines. The most pioneering example to utilize the catalytic functionalization of α-amino anion equivalents to arrive at enantioenriched α-alkyl © 2017 American Chemical Society

Received: March 21, 2017 Published: May 4, 2017 5984

DOI: 10.1021/acs.inorgchem.7b00739 Inorg. Chem. 2017, 56, 5984−5992

Article

Inorganic Chemistry Scheme 1. Pd-Catalyzed Arylation of Imine Reported by Stephen L. Buchwald’s Group

Scheme 2. Proposed Catalytic Cycle of Asymmetric Arylation of Aldimine 2

well as their Cartesian coordinates, are given in the Supporting Information.

2. COMPUTATIONAL METHODS All calculations were performed using the Gaussian09 program package.37 The hybrid density functional B3LYP38−40 was employed for geometry optimizations. 6-31G(d, p)41,42 basis set was employed for nonmetal atoms, and LANL2DZ43−45 was used for Pd and Na atoms. Harmonic vibrational frequencies were computed at the same level to get the entropic corrections and to verify the nature of stationary points. The minimum-energy structures have positive eigenvalues of the Hessian matrix, whereas the transition states have only one negative eigenvalue. When necessary, intrinsic reaction coordinate (IRC) calculations were performed to verify the right connections among a transition state and its forward and reverse minima.46 Natural bond orbital (NBO) analyses were performed at the B3LYP/[6-31G(d, p)+LANL2DZ] level using NBO6.47 Because the M06 functional48 includes noncovalent interactions and can give accurate energies for transition-metal systems, single-point calculations with solvation effects modeled by SMD49 were applied for all gasphase-optimized structures at the M06/[6-311++G(d, p) + LANL2DZ] level. The effectiveness of B3LYP for geometry optimizations and M06 for single-point energy calculations has been demonstrated by numerous studies to successfully produce energy profiles of reactions involving transition-metal complexes.50−57 To ensure that the lowest-energy conformation of intermediates and transition states was presented and discussed in the text, extensive conformational searches were conducted. The free energies are used in the following discussions. Optimized molecular stereoscopic structure figures were prepared using CYLView.58 All optimized structures, as

3. RESULTS AND DISCUSSION Experimentally, [(η-C3H5)PdCl]2, chiral dialkylbiaryl phosphine ligands (Ln, n = 1, 2, 3), and NaOtBu were added as staring materials, in which NaOtBu was used to promote the deprotonation of aldimine 2, [(η-C3H5)PdCl]2, and ligands Ln were used to generate the active catalyst Pd0Ln. To investigate the catalytic mechanism, catalyst Pd0L1 involved reaction that resulted both good yield (82%) and ee (86%) in the experiment, was first calculated. On the basis of our computations and Buchwald’s experimental results,19 the catalytic cycle of the reaction was portrayed in Scheme 2. The whole reaction consists of the following steps: (1) deprotonation of aldimine 2 assisted by base NaOtBu forming an α-amino anion, (2) coordination of α-amino anion to Pd0Ln generating a Pd(0)···N compelex, (3) oxidative addition of PhBr to catalyst Pd0Ln forming the Pd(II)···N intermediate, (4) transmetalation in which the regio- and enantioselectivities are generated, (5) reductive elimination, a key step, in which the new C−C bond is formed between α-amino anion and phenyl to generate the product, (6) releasing of the product and regenerating of the Pd0Ln catalyst. In the following sections, we will discuss the mechanism step by step. 5985

DOI: 10.1021/acs.inorgchem.7b00739 Inorg. Chem. 2017, 56, 5984−5992

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Inorganic Chemistry 3.1. Deprotonation. To initiate the reaction, aldimine 2 should undergo a deprotonation step giving α-amino anion. The free energy profile of deprotonation is depicted in Figure 1.

interact with PdL1 than 1. And electrons transfer from the HOMO of Int3 to the LUMO of PdL1. The free-energy profile of this process is portrayed in Figure 3. The total free energy of initial reactants and active catalyst (1 + 2 + NaOtBu + PdL1) is set as the reference for the catalytic cycle. The coordination of Int3 gives T-shaped intermediate Int4 in which both N and Na interact with Pd center. Consistent with the energies of HOMOs and LUMOs, Int4 is more favorable in thermodynamics by 10.5 kcal/mol than Int4′, which is the intermediate after 1 coordination. The NBO charge of Int3 moiety in Int4 is increased to 0.096 from neutral after coordination, and the charge of Pd center becomes more negative to −0.211 from −0.162. However, if 1 coordinates to PdL1, the electrons transfer from the HOMO of PdL1 to the LUMO of 1. The NBO charge of 1 moiety in Int4′ is decreased from neutral to −0.141, and the charge of Pd center increases from −0.162 to 0.007. Following Int4 is the oxidative addition of 1. However, as 1 approaches Pd center, the 2-azaallyl anion deviates from Pd owing to the steric hindrance. The distance of N−Pd is 5.192 Å in Int5. In the oxidative addition step, 2-azaallyl anion is immobilized by the interaction between N and Na+ with the distance between N and Na+ of ∼2.4 Å in Int5, TS5_6, and Int6. Finally, the 2-azaallyl anion again coordinates to Pd giving Int7-Int10, as we located all the possible coordinated complexes. The NBO charges of Pd in Int7-Int10 are increased to ∼0.44 from −0.211 in Int4. If oxidative addition of 1 is prior to Int3 coordination, the transition state TS4′_5′, leading a Tshaped intermediate Int5′, is 5.0 kcal/mol higher in free energy than that of TS5_6. The isomerization of Int5′ gives a triangular coordinated intermediate Int6′, which is 4.9 kcal/mol higher in free energy than Int5′. Then Int3 coordinates to Int5′ and Int6′ via the N atom with Na+ simultaneously interacting with Br, giving Int7-Int10. From the free-energy profiles, it can be seen that the coordination of Int3 followed by oxidative addition of 1 is the favorable path. 3.3. Transmetalation. The free-energy profiles of transmetalation step for Pd−α-C bond formation of Int7−Int10 are portrayed in Figure 4. In this step, Pd transfers from N to α-C atom generating the chiral C asterisked in Int11−Int14. The free-energy barriers of the four transition states are ∼4.3−6.1 kcal/mol, among which TS10_14 is the most favorable one, indicating the transmetalation step is very facile. The generating intermediates Int11 and Int12 are higher in free energy by ∼8 kcal/mol than those of Int13 and Int14. This may be caused by the stronger trans-effect of phenyl than chiral monophosphorus ligand, which destabilizes the Pd−α-C bond, consisting with the longer Pd−α-C bonds of Int11 and Int12 (∼3.0 Å) than those of Int13 and Int14 (∼2.8 Å) and smaller Wiberg bond indexes of Pd−α-C bond for Int11 and Int 12 (0.179 and 0.181) than those of Int13 and Int14 (0.331 and 0.347). The releasing of NaBr gives Int15−Int18. Int15 and Int16 are ∼10 kcal/mol higher in free energy than those of Int17 and Int18. Moreover, in Int15 and Int16, the α-C−N employs η2 coordination mode, and C atom is in trans-position to phenyl group approximately, which is difficult for the following reduction elimination. Thus, the two paths (Int15 and Int16) can be excluded. Instead of that, cis-position of the α-C to phenyl group in Int17 and Int18 is beneficial for the reduction elimination. To explore the regioselectivity of the reaction, the freeenergy profile of the transmetalation step of Int10 for Pd−α′-C bond formation was calculated (Figure 5). Pd transfers from N to α′-C via a transition state TS10_19. The barrier of TS10_19

Figure 1. Free-energy profile in toluene for the deprotonation of 2, along with optimized structures. Partial key bond lengths in blue are given in angstroms.

Base NaOtBu is used in experiment and our calculations to grab the H atom at α′-position of 2. Complex Int1 is first generated from 2 and NaOtBu under the interactions arising from H···O and N···Na. Crossing transition state TS1_2, H atom transfers from C to O, leading a complex between HOtBu and 2-azaallyl anionic sodium. TS1_2 comprises a moderate barrier (13.0 kcal/mol), and the process is favorable in thermodynamics by 6.6 kcal/mol, indicating the deprotonation is very feasible. Then tBuOH departs from 2-azaallyl anionic sodium (Int3). 3.2. Coordination and Oxidative Addition. After the deprotonation, Int3 can coordinate to PdL1 followed by 1 oxidative addition. Alternatively, it can proceed with the reverse sequence in which the oxidative addition of 1 is prior to Int3 coordination. Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies of 1, Int3, and PdL1 were checked first as shown in Figure 2. We can see that the smallest Egap is HOMO(Int3)−LUMO(PdL1) [2.17 eV]. Hence, it is proposed that Int3 will be more facile to

Figure 2. HOMOs and LUMOs of 1, Int3, and PdL1. 5986

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Figure 3. Free-energy profile in toluene for the coordination and oxidative addition steps, along with optimized structures. Partial key bond lengths in blue are given in angstroms.

Figure 4. Free-energy profile in toluene for the transmetalation with Pd−α-C bond formation, along with optimized structures. Partial key bond lengths in blue are given in angstroms.

exists a strong orbital interaction between the px orbital of α-C and the dxz of Pd (Figure 6B). The pz orbitals of α-C and α′-C are primarily constructing the conjugated π orbital, while there is no such interaction between α′-C and Pd center, which may result from the steric hindrance. It follows that the orbital interactions are beneficial for Pd−α-C other than Pd−α′-C bond formation. 3.4. Reductive Elimination and Dissociation. The freeenergy profiles of reductive elimination and dissociation steps are listed in Figure 7, in which the energies of the most

is 11.4 kcal/mol higher than that of TS10_14. We can see, from the structures of TS10_19 and TS10_14, the Pd−N bond in TS10_19 elongates to 2.688 from 2.225 Å (Int10), which is 0.24 Å longer than that of TS10_14 (2.451 Å), and the distance of forming Pd−α′-C is 0.093 Å longer than Pd−α-C. It indicates that TS10_19 is a late transition state. Additionally, the charges of Pd, α-C, and α′-C in TS10_14 and TS10_19 are 0.453, 0.024, 0.048 and 0.451, 0.000, 0.048, respectively, suggesting that the α-C is more electronegative and more active than α′-C both for TS10_14 and TS10_19. Furthermore, there 5987

DOI: 10.1021/acs.inorgchem.7b00739 Inorg. Chem. 2017, 56, 5984−5992

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Figure 5. Free-energy profile in toluene for the transmetalation with Pd−α′-C bond formation, along with optimized structures. Partial key bond lengths in blue are given in angstroms.

are produced after dissociation from Int21 and Int22, and PdL1 is regenerated. The dissociation steps are endoergic for both PR and PS, with PR is more endoergic by 2.6 kcal/mol. However, the whole catalytic processes are exoergic, which will promote the catalyst to initiate the following catalytic cycle. 3.5. Overall Catalytic Reaction Mechanism. The full free-energy profiles of the catalytic cycle are given in Figure 8. According to the energetic span model introduced by Kozuch and Shaik,59,60 the energetic span that serves as the apparent activation energy of catalytic cycle is defined by the energy difference between turnover-frequency (TOF)-determining transition state (TDTS), the TOF-determining intermediate (TDI), and the reaction driving force. From Figure 8, we can see that TS1_2 is TDTS, and Int21 and Int22 are TDIs, for PR and PS products, respectively. The calculated apparent activation energies for two pathways are 34.5 and 32.6 kcal/ mol. By comparing the difference of apparent activation energies (ΔΔG‡ = 1.9 kcal/mol), the S-selective product was preferred over the R-selective one. The calculated ee value 92% at room temperature is in good agreement with the experimentally observed result (ee = 86%). Additionally, we examined the NBO charges of the three sites (N, α-C, and α′-C) for the full catalytic cycle to explore the site selectivity, which are shown in Figure 9. It can be seen clearly that, for the α-C selective path, the natural charges of αC show an evident charge inversion from positive to negative in transmetalation step from TS9_13 to Int13 (0.263 in Figure 9A) and from TS10_14 to Int14 (0.250 in Figure 9B), indicating that α-C is more nucleophilic and that more electrons transfer from Pd to α-C. Thus, it is beneficial for the formation of Pd−α-C bond owing to the strong electronic interaction of α-C and Pd, while the α′-C comprises positive charge in the following transmetalation and reductive elimination steps. For α′-C selective path (Figure 9C), the charge inversion of α′-C (0.124) is weaker than that of α-C in Figure 9A,B. Thus, α′-C is less nucleophilic, and the electronic interaction between α′-C and Pd is weak, which is unfavorable for the formation of Pd−α′-C bond. This is consistent with that Int13 and Int14 are more stable than Int19 in free energy (see Figures 4 and 5) and that the bond distances of Pd−α-C in Int13 and Int14 (2.209 and 2.210 Å, respectively) are shorter than that of Pd−α′-C in Int19 (2.302 Å).

Figure 6. (A) The orbital graph of the HOMO of Int10. (B) Key orbital interactions between Pd, α-C, α′-C, and N atoms.

Figure 7. Free-energy profiles in toluene for the reductive elimination and dissociation steps, along with optimized structures. Partial key bond lengths in blue are given in angstroms.

favorable optimized structures were used. The other highenergy structures optimized in this step are shown in Figures S1−S3. Crossing transition states TS17_21 and TS18_22, the C−C bond is formed generating N-coordinated intermediates Int21 and Int22. The free-energy barriers of TS17_21 and TS18_22 are ∼11 kcal/mol, and they are exoergic by ∼35 kcal/ mol indicating the reductive elimination step is favorable both in kinetics and thermodynamics. Finally, the products PR with R chiral C atom and PS with S chiral C, as shown in Figure 7, 5988

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Figure 8. Free-energy profiles in toluene for the overall catalytic cycle (in kcal/mol).

Figure 9. NBO charge trace profiles for the overall catalytic cycle in the three sites (N, α-C, and α′-C). (A) α(S)-Selective pathway. (B) α(R)Selective pathway. (C) α′-Selective pathway.

From the whole catalytic cycle and energetic span model, we can see that the free energies of TDIs (Int21 and Int22) are critical in determining the enantioselectivity. To further understand the role of ligand in controlling the enantioselectivity, we first analyzed the geometries of Int21 and Int22. In Int21, iPr groups engage in CH···π interactions with the fluorene and benzene (Figure 10A), while there is almost no CH···π interaction between iPr and fluorene in Int22. This proposed noncovalent interactions basis for the CH···π interaction also agrees well with the orbital overlap of LPPd→ π*CN observed in two structures (Figure 10B), which thus increases the stabilization. The noncovalent interaction differences result in the variations of stabilization energy E(2),61 which defines the donating tendency of the lone-pair electrons of Pd to the antibonding of the vicinal CN. The calculated E(2)s of LPPd→π*CN in Int21 and Int22 are 36.5 and 4.2 kcal/mol, respectively. The strong stabilization effect makes the more stable of Int21 over Int22. Furthermore, we designed three truncated model systems (M1−M3) based on the optimized structures of Int21 and Int22 and examined the effect of noncovalent interactions on the energy of Int21 relative to Int22.62,63 Figure 11 shows the structures of Int21 and the corresponding three truncated models M1−M3. Models M1 and M2 represent the effect of noncovalent interactions of the two iPr groups with the fluorene and the benzene ring, respectively, and dinaphthalene

Figure 10. (A) Noncovalent interactions primarily responsible for the enantioselectivity of Int21 and Int22. (B) Molecular orbital overlap between the LPPd donor orbital and the π*CN acceptor orbital in Int21 and Int22.

is reduced to H atom. For M3, the two iPr groups were reduced to H atoms to evaluate the interaction between dinaphthalene, the chirality skeleton, and Pd center. The three models are divided into two parts as substrate imine (denoted as A) and the rest (denoted as B). We calculated the single-point energies of the model structures and their corresponding two parts both 5989

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Figure 11. Structures of Int21 and three truncated models M1−M3.

for R and S conformations considering the solvent effect. The noncovalent interaction difference between S and R in every model is calculated as ΔE(M) = [E(MS) − E(MSA) − E(MSB)] − [E(MR) − E(MRA) − E(MRB)]. Then the total noncovalent interaction difference ΔE is defined as the sum of ΔE(M1), ΔE(M2), and ΔE(M3). The calculated results of Int21 and Int22 are provided in Table 1 (entry 1), from which we can see Table 1. Calculated Noncovalent Interaction Differences between S- and R-Selective Paths R

X

ΔE

ΔE(M1)

ΔE(M2)

ΔE(M3)

L1 L2 L3

iPr c-C5H9 c-C7H13

H H TMS

−9.6 −5.6 −10.3

−4.1 1.6 −3.2

−3.4 −3.0 −4.9

−2.1 −4.2 −2.2

ligand

ee(exp)

ΔΔG‡(exp)a

ee(calc)a

ΔΔG‡(calc)b

L1 L2 L3

86 44 94

1.5 0.6 2.1

92 59 94

1.9 0.8 2.1

a Computed from exp[−(ΔΔG‡)/(RT)], where T = 298 K. Values in kilocalories per mole. bΔΔG‡(calc) = ΔG(calcR) − ΔG(calcS). Values in kilocalories per mole.

a

ligand

a

Table 2. Experimental and Calculated ee Values (%) and Corresponding Experimental and Calculated ΔΔG‡ Values

enantioselectivity mainly arises from the CH···π interaction between c-C7H13 and benzene (ΔE(M2) = −4.9 kcal/mol).

4. CONCLUSIONS The detailed mechanism exploration for Pd-catalyzed asymmetric arylation of aliphatic α-amino anion equivalents using a chiral dialkylbiaryl phosphine as the supporting ligand has been performed by DFT theory. The results indicate that the reaction proceeds via mainly six sequential steps: deprotonation at α′-site of imine, coordination of N atom of α-amino anion to Pd-catalyst, oxidative addition, transmetalation, reductive elimination, and finally the dissociation to release the product and regenerate the catalyst. The transmetalation is a key step on which both regioselectivity and enantioselectivity depend. An intense umpolung signal of α-C site in α-amino anion is found during the transmetalation process from positive to negative by tracing NBO charges for the full catalytic cycle. This result suggests α-C is more nucleophilic and the electronic interaction between α-C and Pd is strong, which is beneficial for the formation of Pd−α-C bond. However, the umpolung is weaker in the α′-C selective path, which is unfavorable for the formation of Pd−α′-C bond. Additionally, the orbital interaction presenting between α-C and Pd center increases the activity of α-C atom. Thus, the regioselectivity of the reaction is affected both by the electronic effect and the orbital interaction. Moreover, according to the energetic span model, the intermediates before the dissociation step are critical in controlling the enantioselectivity. The origin of the enantioselectivity was explored based on the noncovalent interactions of these intermediates between the ligand and the imine moiety. In PdL1-catalyzed reaction, one iPr substituent engages in CH···π interaction with the fluorene in S channel, while there is almost no such interaction in R one. The noncovalent interactions between the ligand and imine moiety result in that the S conformation is more beneficial than the R one. The noncovalent interaction decomposition shows that the difference of noncovalent interactions for PdL1 catalyzed two enantioselective channels primarily arises from the CH···π interactions of iPr groups with the fluorene and the benzene

In kilocalories per mole.

that the values of ΔE(M1) − ΔE(M3) are −4.1, −3.4, and −2.1 kcal/mol, respectively. This result quantifies the contribution of noncovalent interactions between the imine moiety and PdL1 moiety to the energy separation between Int21 and Int22. The present result suggests that the difference of noncovalent interactions for two enantioselective channels primarily arises from the CH···π interactions of iPr groups with the fluorene and the benzene ring. According to the experiment, the enantioselectivity is much sensitive to the nature of the substituent groups on the phosphine ligand. For instance, L1 provides excellent selectivity (ee = 86%). When R is varied to cyclopentyl (c-C5H9), the ee is reduced to 44%. And the ee value is enhanced to 94%, the highest ee detected in the experiment, when R is varied to cycloheptyl (c-C7H13) and X is changed to TMS. Hence, we calculated the catalytic mechanism of PdL2 and PdL3 to investigate the effect of R- and X-substituent on enantioselectivity. The corresponding free-energy profiles for PdL2 and PdL3 are given in Figures S4 and S5. According to the energetic span model, the energetic spans of PdL2-catalyzed S- and Rselective paths are 24.3 and 25.1 kcal/mol. And the values are 29.0 and 31.1 kcal/mol for PdL3. On the basis of our results, the calculated ee values are given in Table 2, from which we can see that the calculated ee values are consistent well with the experiment results. This also confirms that the computing methods we employed and mechanism we proposed are reasonable. The noncovalent interaction analyses are conducted for PdL2 and PdL3 as well in Figures S6 and S7. The results are presented in Table 1. We note that for PdL 2 the enantioselectivity is primarily due to ΔE(M3) (−4.2 kcal/ mol) and that the ΔE (−5.6 kcal/mol) is less than that of PdL1 (−9.6 kcal/mol). The smaller ΔE of PdL2 may be the primary reason for the lower ee value. For PdL3, the marked 5990

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Inorganic Chemistry

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rings. Besides, for different ligand, the primary noncovalent interaction impacting the enantioselectivity is different.

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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.inorgchem.7b00739. Computed potential-energy profiles, free-energy profiles, noncovalent interactions, Cartesian coordinates of all optimized structures (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Fang Huang: 0000-0003-4801-7111 Jianbiao Liu: 0000-0002-2550-3355 Dezhan Chen: 0000-0002-2192-4582 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by National Natural Science Foundations of China (Nos. 21375082 and 21403132). REFERENCES

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