Asymmetric Hydroformylation Catalyzed by RhH(CO)2[(R,S)-Yanphos

Article pubs.acs.org/JPCA

Asymmetric Hydroformylation Catalyzed by RhH(CO)2[(R,S)‑Yanphos]: Mechanism and Origin of Enantioselectivity Ming Lei,*,† Zhidong Wang,† Xiaojie Du,† Xin Zhang,† and Yanhui Tang‡ †

State Key Laboratory of Chemical Resource Engineering, Institute of Materia Medica, College of Science, Beijing University of Chemical Technology, Beijing 100029, P. R. China ‡ College of Material Science and Engineering, Beijing Institute of Fashion Technology, Beijing 100029, P. R. China S Supporting Information *

ABSTRACT: Asymmetric hydroformylation (AHF) catalyzed by transition metal (TM) complexes bearing chiral phosphorus ligands is one of the most powerful synthetic ways that could provide chiral aldehydes directly from alkenes and syngas in one step. Experiments have proved the efficiency of Rh catalyst with hybrid phosphorus ligands owning two different phosphorus moieties in AHF. Herein the origin of enantioselectivity of AHF catalyzed by RhH(CO)2[(R,S)-Yanphos] was studied at M06/BSI level using the density functional theory (DFT) method to unveil a fundamental understanding on factors contributing to the efficiency in AHF. The alkene insertion step is supposed to be the chirality-determining step in the whole catalytic cycle of the Rh-Yanphos system. Four possible pathways of styrene (Sub1) insertion step (pathways R1, S1, R2, and S2) were discussed; the calculated results indicate that pathways R1 and S2 are proposed to be two dominant alkene insertion pathways and that styrene tends to adopt apical coordination mode (A mode) to Rh center in pathways R1 and S2 compared to equatorial coordination mode (E mode) in pathways R2 and S1. The enantioselectivity of AHFs of ten alkene substrates (CH2CH−R, RPh, C(O)OCH3, Ph-(p)-Me, Ph-(p)-OMe, Ph(p)-iBu, Ph-(p)-F, Ph-(p)-Cl, Ph-(o)-F, OC(O)−Ph and O−Ph, corresponding alkenes are abbreviated as Sub1 to Sub10, respectively) were also investigated. The predicted chiralities agree well with experimental results. The present work suggests that the relative stabilities of coordination modes (A/E mode) of alkene to 2 (RhH(CO)[(R,S)-Yanphos]) might be of importance in the enantioselectivity of AHF catalyzed by Rh-Yanphos.

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INTRODUCTION Hydroformylation (oxo process) is a ripe technology and the largest industrially homogeneous catalytic process with a capacity of oxo products over 6 × 106 tons per year.1,2 Cobalt-based industrial processes and rhodium-based ones are the most popular oxo processes in the past 30 years. With the dramatic growing demand for chiral compounds in pharmaceutical, agrochemical, and fine chemical industries, until now a lot of useful asymmetric synthesis or separation methods have emerged for producing pure chiral products. Asymmetric hydroformylation (AHF) catalyzed by transition metal (TM) complexes bearing chiral phosphorus ligands is one of the most powerful synthetic protocols to achieve optical active aldehydes (see eq R1), which are well-known to be important precursors of pharmaceutical products, biological active compounds, fine chemicals, and so on.3,4 It could provide chiral aldehydes directly from alkenes and syngas (CO/H2) in one step. One basic challenge for the further commercialization of AHF is to balance its enantioselectivity, reactivity, and regioselectivity. Some highly enantioselective hydroformylation are found to © 2014 American Chemical Society

proceed at low temperature with relatively low reactivity. Another challenge is to prevent it from the racemization of chiral aldehyde products especially at an industrial accepted reaction temperature. RCHCH 2 + CO + H 2 → RC*H(CHO)CH3 + RCH 2CH 2CHO

(R1)

The TM catalysts bearing a chiral ligand play a very important role in the formation of chiral oxo products.5−8 The first application of AHF was performed in 1972, which used catalysts like platinum−diphosphine complex but suffered a low regioselectivity and chemoselectivity.9,10 It has been paid more and more attention in the past 10 years to develop and Special Issue: International Conference on Theoretical and High Performance Computational Chemistry Symposium Received: February 24, 2014 Revised: April 13, 2014 Published: April 15, 2014 8960

dx.doi.org/10.1021/jp501941b | J. Phys. Chem. A 2014, 118, 8960−8970

The Journal of Physical Chemistry A

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1:1). Rh-Yanphos catalyst’s high activity and excellent enantioselectivity make it a promising industrial catalyst for the commercialization of AHF in the future. Since Wilkinson et al. proposed a conceivable mechanism of hydroformylation in 1968, the mechanism mediated by RhH(CO)2(PPh3)2 may have two possible pathways, associative or dissociative mechanism. Theoretical and experimental literatures supported the mechanism that hydroformylation prefers the dissociative mechanism to the associative mechanism.23−27 The dissociative mechanism was adopted in this study. As shown in Scheme 2, the dissociative catalytic mechanism of AHF catalyzed by RhH(CO)2[(R,S)-Yanphos] (1) depicts fundamental reaction steps to produce linear aldehyde and chiral branched aldehydes with R or S conformations. Blue, green, and red lines represented pathways leading to R, S, and linear aldehydes, respectively. Styrene is used as the default alkene substrate of the asymmetric hydroformylation. The whole catalytic cycle includes four key elementary steps: styrene insertion (3 → 4), CO insertion (5 → 6), H2 oxidative addition (6 → 8), and aldehyde reductive elimination (8 → 2). In the past decades, it is well understood for the mechanism of hydroformylation.11,28−33 Morokuma et al. and Cundari et al. systematically studied the mechanism of olefin hydroformylation catalyzed by RhH(CO)2(PH3)2 using theoretical methods, respectively.30,31 Quantitative structure−property or structure− activity relationship (QSPR/QSAR) approaches were employed to describe the nature of enantioselectivity and activity of AHF, which opened a new angle of view in this field.11 In addition, Carbό et al. assessed the enantioselectivity in Rh catalysts with aminophosphane phosphinite (AMPP) and Binaphos ligand using QM/MM method. The alkene insertion step was assumed to be the chirality-determining step. They also found that the enantioselectivity was correlated with coordination modes of bidentate ligand with TM center.34 For example, RhH(CO)2[(R,S)-Binaphos] is five-coordinate with a TBP geometrical structure. The two phosphorus ligands could coordinate either in equatorial−equatorial (ee1 or ee2) mode or equatorial−apical (ea1 or ea2) mode (see Scheme 3).11 Although the phosphite moiety of the Binaphos ligand (phosphine−phosphite ligand, P−OP) is a poor σ donor and a good π acceptor, Takaya et al. have characterized an isomer of Rh-Binaphos with the phosphite moiety in the apical position in experiments (ea1 mode in Scheme 3).21 Using lowtemperature nuclear magnetic resonance (NMR) spectroscopy, Jäkel et al. observed the equilibrium between two equatorial− apical isomers of Rh-Binaphos, while the ea1 mode was in the majority and the ea2 mode was in the minority.35 The steric effect of Binaphos ligand may account for this coordination preference, which the phosphine moiety is put in the less crowded equatorial position. Therefore, ea1 coordination mode could be applicable in Rh-Yanphos system due to the structural and electronic similarity between Binaphos and Yanphos ligand. There could be an equilibrium between those d8 fivecoordinated Rh(H)(CH2CHR)(CO)(Yanphos) isomers via Berry pseudorotation, which could explain the equilibrium between ea1 and ea2 coordination mode observed by experiment.30,35,36 The catalyst bearing hybrid phosphorus ligand with two different phosphorus moieties has been proved to be efficient in AHF. Meanwhile, ligand modification may affect activity of AHF while mediating enantioselectivity and changing enantioselectivity and reactivity significantly like Rh-Binaphos and Rh-

synthesize efficient TM catalysts with a high enantioselectivity and reactivity for AHF. In order to construct an efficient stereoinduction environment of TM catalysts, chiral ligand design becomes a major way to give a higher enantiomic excess (ee) value of AHF.11,12 Some experiments have proved the efficiency of Rh catalyst with hybrid phosphorus ligands owning two different phosphorus moieties in AHF.13−17 In 1993, Takaya et al. made a breakthrough in AHF of arylethene and some specified functionalized olefins such as vinyl acetate and N-vinylphthalimide using Rh catalyst with phosphine− phosphite ligand (Rh-Binaphos) (see Scheme 1A), which Scheme 1. Representative Structures of Rh Catalysts with ea1 Coordination of the Phosphorus Liganda

a

(A) RhH(CO)2[(R,S)-Binaphos]; (B) RhH(CO)2[(R,S)-Yanphos]. (R,S)-Binaphos denotes (R,S)-phosphine−phosphite ligand and (R,S)Yanphos denotes (R,S)-phosphine−phosphoramidite ligand.

could give 95% ee and more than 86/14 in b/l ratio.18 Different configuration combinations of two binaphthyl moieties of the Rh-Binaphos catalyst were observed with different catalytic enantioselectivity: (R,S)-Binaphos or (S,R)-Binaphos (called matched combination) bearing 2-fold axial chiral ligand could yield unprecedented ee value, but (S,S)-enantiomer and (R,R)enantiomer (called mismatched combination) have a detrimental effect on the enantioselectivity of AHF.19−22 A high enantioselectivity was obtained at low temperature, while the reaction rate is relatively low in the Rh-Binaphos system. Meanwhile, at a relatively high temperature the racemization of chiral aldehyde appeared and decreased the enantioselectivity. However, the temperature is of importance for the industrialization of AHF to operate the reaction with an acceptable reaction rate. Thus, it is still desirable to optimize, design, and synthesize TM catalyst without racemization in AHF, which could own higher enantioselectivity, reactivity, and regioselectivity. In 2006, Zhang et al. developed Rh-Yanphos catalyst with a novel hybrid phosphine−phosphoramidite ligand (see Scheme 1B),23,24 which could reach 98% ee for styrene and 96% ee for vinyl acetate (b/l ratio could achieve 7.2) in AHF catalyzed by RhH(CO)2[(R,S)-Yanphos] under the condition (temperature = 60 °C, CO and H2 pressure ratio of syngas = 8961



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Scheme 2. Dissociative Mechanism of Asymmetric Hydroformylation (AHF) Catalyzed by RhH(CO)2[(R,S)-Yanphos]a

a

L indicates linear, and R/S represents intermediates along the pathway leading to the R/S aldehyde product. Blue line represents the pathway producing R chiral aldehyde, green line represents the pathway producing S chiral aldehyde, and red line represents the pathway producing linear aldehyde.

structures.39 The molecular cavity was constructed using the UFF radius.40 All transition states (TSs) were confirmed by only one imaginary frequency, and the normal mode corresponded to the expected reaction path. Intrinsic reaction coordinate (IRC) calculations were performed in order to confirm more details around TSs and corresponding intermediates (INTs). Structures of INTs and TSs were optimized without any symmetry constraints. All relative energies of stationary points along the reaction pathway were relative to corresponding 1. All potential energies were presented with zero-point vibrational energy correction (ZPE). All Gibbs free energies were calculated at 298.15 K, which was lower than the experimental temperature (333.15 K). Energies discussed in the following parts are relative potential energies with ZPE unless stated. Because INTs like 2 in this catalytic cycle are too large to be a practical calculated model in this theoretical study, dimethylene group (−(CH2)2− group) and hydrogen atoms were used in a simplified model to replace the naphthyl groups and phenyl groups in this article (see bold bond parts in full model of Yanphos ligand in Figure 1A,B). The steric and electronic characters of Yanphos ligand could be still kept in part. The structures of the catalyst precursor (1: RhH(CO)2[(R,S)-Yanphos]), catalytic active species (2: RhH(CO)[(R,S)-Yanphos]), and their simplified models are depicted in Figure 1. The calculated geometrical parameters in simplified models of 1 and 2 at the M06/BSI level agree well with those in full model at the M06/BSII level (see Figure 1C,D). For example, the Rh1−H2, Rh1−C5 and Rh1−P12 bond lengths of 1 are 1.603 (1.617, 1.618) Å, 1.939 (1.940, 1.937) Å, and 2.370

Scheme 3. Schematic Representation of Four Possible Geometrical Isomers of the Hydrido Carbonyl Catalyst Precursor (1, RhH(CO)2[(R,S)-Binaphos])

Yanphos. It is still unclear to explain the relationship between catalysts’ structures and their related catalytic activities, like enantioselectivity. In the viewpoint of substrate−catalyst interaction, this article investigated the nature of AHF catalyzed by RhH(CO)2[(R,S)-Yanphos] using M06 density functional theory (DFT) method. Four possible alkene insertion pathways were discussed, and the origins of enantioselectivities of ten alkene substrates’ AHFs were explored.

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COMPUTATIONAL DETAILS All calculations were carried out using hybrid density functional M06 method and Gaussian 09 program package. 37,38 LANL2DZ pseudopotential basis set was used for Rh center, and 6-31+G** basis set was used for the other atoms. We denote this approach as M06/BSI. In the optimization of a full model catalyst, LANL2DZ basis set was used for Rh center, and 6-31G* basis set was used for the other atoms, we denote this approach as M06/BSII. All single-point solvation energies were calculated using the continuum SMD model, and benzene was used as the solvent based on the gas-phase optimized 8962



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Figure 1. Structural comparison of the catalyst precursor RhH(CO)2[(R,S)-Yanphos] (1) and catalytic active species RhH(CO)[(R,S)-Yanphos] (2). (A) Full model of 1. (B) Full model of 2. (C) Simplified model of 1. (D) Simplified model of 2. In panels C and D, the optimized key geometrical parameters in the first, second, and third rows are listed in plain text for the simplified model at M06/BSI level, in italic text for the simplified model at M06/BSII level, and in bold text for the full model at M06/BSII level, respectively (bond lengths in Å). The main atomic serial numbers are also labeled.

preferred in the apical site and the better π acceptor is preferred in the equatorial site, Yanphos ligand prefers to adopt ea1 coordination mode, which places the larger phosphine moiety in the less crowded equatorial site similar to Binaphos ligand.34 This fact was found not only by experiments but also by computational studies that the bidentate Binaphos ligand coordinates preferably in an equatorial−apical manner (ea1 or ea2 in Scheme 2).11,21,34 In this study the ea1 coordination mode of Yanphos ligand was used as the preferable structure of Rh-Yanphos catalyst. First, the catalyst precursor RhH(CO)2[(R,S)-Yanphos] (1) generates the catalytic active species (2: RhH(CO)[(R,S)Yanphos]) with a square-planar structure by means of the dissociation of one carbonyl ligand on the equatorial plane. The Rh1−H2 bond is placed in the apical axis, the hydride (H2 atom) bonding with Rh center is trans to the phosphorus atom (P12) of phosphoramidite moiety, and the carbonyl ligand is trans to the phosphorus atom (P11) of phosphine moiety in ea1 mode of Yanphos. Alkene Insertion Step. Because of multiple kinetic scenarios caused by ea1, ea2, ee1, and ee2 coordination modes of Yanphos ligand of 1, the whole catalytic cycle of AHF catalyzed by Rh-Yanphos complex is complicated. Herein is only the ea1 coordination mode of 1 considered, which is assumed to be the most preferable coordination mode in AHF catalyzed by RhH(CO)2[(R,S)-Binaphos].11,34,11,35 As shown in Figure 2, 2 could form coordination sites on two sides of C5−H2−Rh1−P11 plane named by enantioface. Re and Si

(2.364, 2.334) Å, respectively. Those of 2 are 1.627 (1.641, 1.641) Å, 1.886 (1.885, 1.885) Å, and 2.338 (2.327, 2.303) Å, respectively (values in parentheses are calculated results in the simplified model at M06/BSII level and in the full model at M06/BSII level, respectively). Those also support the efficiency of simplified models, the reliability of the use of M06 method, and the basis set combination in this study. Meanwhile, the π−π stacking interaction between the phenyl group of phosphine moiety and the naphthyl ring of phosphoramidite moiety was also observed in the optimized 1 and 2 using a full model at the M06/BSII level, the distances between phenyl ring and naphthyl ring in 1 and 2 are around 3.7 and 4.0 Å, respectively. The main parameters of catalyst precursor and catalytic active species in simplified and full model were listed in Supporting Information.

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RESULTS AND DISCUSSION As shown in Scheme 2, the catalytic cycle of asymmetric hydroformylation catalyzed by RhH(CO)2[(R,S)-Yanphos] consists of four key elementary steps such as alkene insertion, CO insertion, H2 oxidative addition, and aldehyde reductive elimination. According to the direction of hydride transfer and the alkene coordination mode in the alkene insertion step, the pathway from INT 3 is divided into three pathways leading to iso-aldehydes (R and S aldehydes) and linear aldehyde. This work is based on the assumption that the major catalytic active species of 1 would own the structure with an apical phosphite ligand (ea1 mode). Although the better σ donor is 8963



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and S1 are pathways leading to Re and Si intermediates on the front side of the enantioface, and pathways R2 and S2 are those leading to Re and Si intermediates on the back side (see Figure 2). INT 3R1 is intermediate 3 with Re conformation in pathway R1. Figure 3 describes geometrical parameters of stationary points along four possible pathways in the alkene insertion step. Styrene coordinates with Rh center of 2 and forms a η2-olefin adduct (3). The adduct has four different isomers 3R1, 3R2, 3S1, and 3S2. These isomers adopt a TBP geometrical structure, while styrene is parallel or perpendicular to the apical Rh1−H2 bond. The coordination of styrene to 2 increases the C3C4 bond length to 1.347, 1.399, 1.406, and 1.368 Å in 3R1, 3R2, 3S1, and 3S2, respectively (1.334 Å in styrene). Then, styrene inserts into the Rh1−H2 bond to generate an unsaturated Rh-aryl INT (4) via a four-membered ring TS (Rh1−H2−C3−C4 ring). In pathways R2 and S1 from 3 to 4, there does occur a structural change to rotate C3C4 double bond out of the equatorial plane, and the bond becomes aligned with the axial Rh1−H2 bond. However, it is not necessary for 3 in pathways R1 and S2. The hydride (H2) transfers to C3 atom, and the alkene insertion step is completed, Rh1−H2 bond is broken, and Rh1− C4 bond is formed simultaneously. Four TSs (TS3R1-4R1, TS3R2-4R2, TS3S1-4S1, and TS3S2-4S2) were confirmed by IRC

Figure 2. Two possible alkene coordination approaches to both sides of the entantioface of the catalytic species (2) in asymmetric hydroformylation (AHF) catalyzed by Rh-Yanphos adopting ea1 coordination mode.

intermediates of 3 could be formed by means of alkene coordination to the Rh center of 2 on its front side or back side. The alkene insertion pathways on the front side are labeled by route 1, and those on the back side are labeled by route 2. Thus, four possible alkene insertion pathways (pathways R1, S1, R2, and S2) may exist, which could lead to Re and Si intermediates of 4 via the alkene insertion step. Pathways R1

Figure 3. Selected geometrical parameters of optimized structures (bond lengths in Å) for stationary points in the alkene insertion step and the potential energies (kcal/mol) relative to 1 at the M06/BSI level. 8964



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Figure 4. Representation of eight possible alkene coordinations to the catalytic species (2) in asymmetric hydroformylation (AHF) catalyzed by RhYanphos adopting ea1 coordination mode. A/E mode means the alkene uses apical/equatorial coordination mode. 3R1ax means intermediate 3 with A mode in pathway R1.

Figure 5. Energy profiles (kcal/mol) of the styrene insertion step in AHF. The favorable pathways, pathways R1 and S2, are shown in bold red and bold black lines, respectively. NA means INT 3 with apical coordination mode is not available.

and frequency analysis owning only one imaginary frequency. The Rh1−C4 bond lengths in 4R1, 4R2, 4S1, and 4S2 are 2.161, 2.154, 2.169, and 2.160 Å, respectively. INT 4 are deformed with a square-pyramidal (SPy) structure, and the carbonyl ligand is trans to the phenylethyl group with Re/Si conformation. Equatorial Vertical Coordination Mode and Equatorial In-Plane Coordination Mode. Interestingly, styrene could coordinate with 2 in either equatorial in-plane position

along pathways R2 and S1 or in equatorial vertical position along pathways R1 and S2. In INT 3R1 and 3S2, the C3C4 double bonds of styrene are almost parallel to the Rh1−H2 bond using equatorial vertical coordination mode (abbreviated as A mode). However, in 3R2 and 3S1, the double bonds are found to be perpendicular to the Rh1−H2 bond using equatorial in-plane coordination mode (abbreviated as E mode). The C3C4 double bonds of alkenes with E mode in pathways R2 and S1 have to orient toward the axial Rh1−H2 8965



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Figure 6. Quadrant diagram representation of four transition states (TSs) in the alkene insertion step: (A) Pathway S1, (B) pathway R2, (C) pathway R1, and (D) pathway S2. The two shaded quadrants represent space that is occupied due to steric effect of Yanphos ligand.

chirality-determining step in AHF catalyzed by Rh-Yanphos and Rh-Binaphos complexes.11,19,34 This study agrees with this assumption that the enantioselectivity of this system should result from the alkene insertion step. Thus, only was the alkene insertion step discussed herein, a systemic theoretical study on the whole catalytic cycle of AHF catalyzed by Rh-Yanphos would be reported in details elsewhere. In the deuterioformylation experiment of styrene catalyzed by Rh-Binaphos, Takaya et al. found that the deuterium label exclusively incorporated in the formyl group and the position β to the formyl group of the products, which clearly demonstrated the irreversibility of the alkene insertion step at total pressures of 20−100 atm (D2/CO = 1/1). In such situation, the regioselectivity and enantioselectivity of AHF catalyzed by Rh-Binaphos catalyst are determined by the alkene insertion step. At the same time, Takaya et al. also showed that the reaction of styrene in the alkene insertion step is reversible at 1 atm (D2/CO = 1/1).20 In 2009, Landis’ experiment indicated that the hydroformylation reaction of styrene is reversible at 80 psi,43 which is actually consistent with Takaya’s conclusions. Herein, Yanphos ligand is similar to Binaphos ligand in structure, and the Rh-Yanphos catalyzed reaction proceeded at around 20 atm in Zhang et al.’s experiments.23 Hence, it is conceivable in this study that the alkene insertion step is irreversible and that it is the chirality-determining step in the whole catalytic cycle. It should be understood that the pathway from 3 with E mode will be higher in energy barrier than that from 3 with A mode. In pathways R2 and S1, styrene has to spend energy to procure a skeletal structural change by rotating the C3C4 double bond out of the equatorial plane to align with the axial Rh1−H2 bond. In pathway R1, 3R1eq with E mode could transform into 3R1ax with A mode to finish the alkene insertion although the former is lower in energy than the latter. However, the latter is not necessary to isomerize into the former to finish the alkene insertion step. In most cases, those INTs with A mode owning a higher energy like 3R1ax are ignored and regarded as unstable intermediates. The deuterioformylation with the Rh-Binaphos catalyst demonstrates that the alkene insertion step is mostly irreversible.20 The alkene coordination mode may alter its dominant reaction pathway. Therefore, the intermediate 3 with A mode should not be ignored according to this study. Two Dominant Reaction Channels. It should be noted that the steric effect of the ligand plays an important role in the preference of the catalytic reaction pathway. If a full model was considered, INT 3 with A mode may not exist due to a crowded hybrid phosphine−phosphoramidite ligand environment. It is to say, the alkene coordination adduct (3) may be unstable in the alkene insertion step of AHF. However, it could

bond, while it is not required for those with A mode in pathways R1 and S2. There does exist a skeletal change from 3 with E mode to TS with A mode in pathways R2 and S1. As shown in Figure 4, we listed all possible isomers of 3 (3R1eq, 3R1ax, 3S1eq, 3S1ax, 3R2eq, 3R2ax, 3S2eq, and 3S2ax) with A/E mode leading to iso-aldehydes despite of the steric effect of Yanphos ligand. 3R1ax means intermediate 3 with A mode in pathway R1, 3R1eq means intermediate 3 with E mode. For instance, one of 3R1ax and 3R1eq or both may exist in pathway R1, but they should have the same transition state with A mode in this simplified system. If a full model was used, 3R1ax and 3R1eq were expected to have similar but different TSs along pathway R1 due to the steric hindrance of the naphthyl group of Yanphos ligand. Although this is a little different from the previous points about the SPy structural TS in the alkene insertion step beginning from η2-olefin adduct (3),32 it does not conflict with those points because the catalytic species (3) is rigid in the structure due to the bidentate Yanphos ligand. The preference and relatively stability of A mode or E mode depends on the substrate−ligand interaction in the alkene insertion step. Herein the potential energies of 3R1eq, 3R1ax, 3S1eq, 3S1ax, 3R2eq, 3R2ax, 3S2eq, and 3S2ax are 8.3, 13.6, 8.6, NA, 8.4, NA, 11.7, and 12.6 kcal/mol, respectively (see Figure 5). NA means that INT 3 with A mode are not found in pathways R2 and S1, which should be unstable due to the steric effect of the ligand. It is obvious and reasonable that 3 with E mode such as 3R1eq and 3S2eq are lower in energy than 3 with A mode such as 3R1ax and 3S2ax because a lot of theoretical studies have verified the energetic and site preference of axial H and equatorial alkene of η2-olefin adduct (3).31,36 This could be owing to orbital preferences between alkene and square-planner intermediate (2).41,42 The axial TM−ligand (TM−L) bond in the TBP is stronger than the equatorial one because the axial σ TM−L bond could use the dz2 orbital, but the equatorial TM−L bond could only use s and p orbitals of TM center. However, the equatorial TM−alkene bond is stronger than the axial one because of the stronger back-donation to a π* orbital.41 The calculated results on A and E mode of alkene are consistent with previous theoretical conclusions. In addition, some INTs like 3R2ax and 3S1ax are even unstable along pathways R2 and S1. This implies that the coordination modes of alkene might influence the favorable alkene insertion pathway. Energy Profile of the Styrene Insertion Step. Figure 5 plots the potential energy profiles of the styrene insertion step along pathways R1, S1, R2, and S2. They are exothermic by 8.4, 4.5, 3.8, and 4.2 kcal/mol, respectively. The potential energy barriers are 6.2, 8.5, 8.2, and 8.3 kcal/mol, respectively. The solvation energies calculated in benzene are shown in Table S4 (Supporting Information), which have little influence on the energy barriers. The alkene insertion step is proposed to be the 8966



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Figure 7. Potential energy profiles (kcal/mol) in the alkene insertion step of different alkene substrates in AHF. Text in parentheses is the coordination mode in INT 3.

enantioselectivity of AHF catalyzed by Rh-Yanphos based on the substrate−ligand interaction. Interestingly, Herrmann et al. pointed out the stereodifferentiation in TBP-like Rh complexes with an ea-coordinated C2-symmetric P−P ligand.19 Two of four alkene insertion pathways could favorably form Re and Si intermediates. This explains the fact that some Rh catalysts with C2-symmetric P−P ligand are high enantioselective in homogeneous hydrogenation but poor in AHF.44 In this study, the quadrant diagram explains the preference of pathways R1 and S2 in Figure 6. The former pathway favors the formation of R aldehyde, and the latter favors the formation of S aldehyde. Two favored pathways are competitive. The difference between pathway R1 and pathway S2 may foster high ee values of certain aldehyde conformation (R or S). The quadrant diagram only gives qualitative information in AHF with Rh-Yanphos and could not concisely predict preferred pathways. The calculated results verified two dominant alkene insertion pathways in the stereodifferentiation of alkene with Rh-Yanphos together with the quadrant diagram theory. In the styrene insertion step above, the energy barrier of pathway R1 forming INT Rh-Re-aryl (4R1) is 2.1 kcal/mol lower than that of pathway S2 producing Rh-Si-aryl (4S2). Enantioselectivity of AHF with Rh-Yanphos. In order to further investigate the enantioselectivity of AHF catalyzed by RhH(CO)2[(R,S)-Yanphos], ten alkene substrates (CH2 CH−R, RPh, C(O)OCH3, Ph-(p)-Me, Ph-(p)-MeO, Ph(p)-iBu, Ph-(p)-F, Ph-(p)-Cl, Ph-(o)-F, OC(O)−Ph and O− Ph, corresponding alkenes are abbreviated as Sub1 to Sub10, respectively) were studied in the alkene insertion step along pathways R and S on the enantioface of 2. Figure 7 describes the potential energy profiles of the alkene insertion step. The calculated potential energy barriers along pathway R for Sub1−

be conceivable that pathways R2 and S1 would be inhibited due to the steric effect if a full catalytic model was used. Therefore, pathways R1 and S2 are regarded as two dominant pathways to form INT 4 with phenylethyl group adopting Re/Si conformation. This is in agreement with experimental data about the preferable alkene insertion pathways in the binding pocket formed by Rh-Yanphos to avoid the steric repulsion effect.23 Figure 6 describes the quadrant diagram of TSs of four alkene insertion pathways. In the quadrant diagram, the plane contains the Rh−H axis and is parallel to the alkene plane with the equatorial ligands lying in front of the plane. The π−π stacking interaction between the phenyl group of phosphine moiety and the naphthyl ring of phosphoramidite moiety was observed in the optimized 1 and 2 using a full model at the M06/BSII level; this will narrow the region of alkene coordinating with 2 in pathways R2 and S1 in a real system. As mentioned above, the alkene insertion pathways S1 and R2 (see Figure 6A,B) using E mode would be inhabited due to the steric hindrance of naphthyl rings bonding with N13 and O15 atoms in the Rh-(R,S)-Yanphosl system. Integrating with the quadrant diagram, pathways R1 and S2 (see Figure 6C,D) in the alkene insertion step are proposed to be two major pathways leading to R and S chiral aldehyde products in this study. Considering the steric effect of Yanphos, pathway R1 on the front side of the enantioface and pathway S2 on the back side will be discussed in the following section. This study further confirms Re and Si binding pockets for the alkene insertion on the enantioface in the viewpoint of theoretical calculations. It is supposed to be important in the enantioselectivity in ea1/ea2 coordination mode of the Yanphos ligand. This is hoped to account for the 8967



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Table 1. Potential Energy Barriersa in Pathways R1 and S2, the Differencesa in Energy Barrier between Two Pathways, and Calculated and Experimental ee Values of the Produced Aldehydes for AHF of Different Alkene Substrates ΔER1b ΔES2c ΔΔEd calcd eee exptl eef

Sub1

Sub2

Sub3

Sub4

Sub5

Sub6

Sub7

Sub8

Sub9

Sub10

6.2 (A) 8.3 (A) 2.1 94 (R) 98 (R)

9.5 (E) 5.7 (A) −3.8 100 (S) NA

6.3 (A) 10.1 (A) 3.8 100 (R) 99 (R)

9.2 (A) 10.4 (A) 1.2 77 (R) 98 (R)

6.1 (A) 8.4 (A) 2.3 96 (R) 98 (R)

6.0 (A) 9.1 (A) 3.1 99 (R) 98 (R)

6.3 (A) 9.2 (A) 2.9 99 (R) 98 (R)

5.8 (A) 7.4 (A) 1.6 87 (R) 98 (R)

12.3 (E) 9.9 (A) −2.4 99 (S) 93 (S)

9.7 (A) 11.5 (E) 1.8 91 (R) NA

a

Unit: kcal/mol. bThe potential energy barriers in pathway R1: A or E in parentheses denotes corresponding apical or equatorial coordination mode of the alkene substrate to the Rh center. cThe potential energy barriers in pathway S2: A or E in parentheses denotes corresponding apical or equatorial coordination mode of the alkene substrate to the Rh center. dΔΔE = ΔES2 − ΔER1. eThe ee values are calculated by the Arrhenius equation (calcd ee). Text in parentheses is predicted aldehyde chirality (R or S). According to ee = (R − S)/(R + S) and the Arrhenius equation, we could obtain ee = (exp(ΔΔE/RT) − 1)/(exp(ΔΔE/RT) + 1) to calculate ee values. fThe ee values are experimental ee values (exptl ee). Text in parentheses is experimental aldehyde chirality (R or S). NA means not applicable.

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CONCLUSIONS In summary, the enantioselectivity of asymmetric hydroformylation (AHF) catalyzed by RhH(CO)2[(R,S)-Yanphos] was studied using the DFT method. The alkene insertion step is supposed to be the chirality-determining step in the whole catalytic cycle of this system. Four possible pathways leading to R/S aldehyde from styrene (Sub1) were discussed; the potential energy barriers of the alkene insertion step of pathways R1, R2, S1, and S2 are 6.2, 8.2, 8.5, and 8.3 kcal/ mol, respectively. Pathways R1 and S2 were proposed to be two dominant alkene insertion pathways, which also validated the importance of stereoinduction due to the substrate−ligand interaction. In pathways R1 and S2, styrene tends to adopt equatorial vertical coordination mode (A mode) to Rh center, but for pathways R2 and S1, the coordination mode of styrene is apt to adopt the equatorial in-plane one (E mode) in this calculation. Although the intermediate 3 with A mode is higher in energy than that with E mode, it should not be ignored because it may result in a lower energy barrier in the alkene insertion step. The calculated results indicate that the alkene coordination mode may alter dominant reaction pathway. The enantioselectivity of AHFs of ten alkene substrates (Sub1 to Sub10: CH2CH−R, RPh, C(O)OCH3, Ph-(p)-Me, Ph(p)-OMe, Ph-(p)-iBu, Ph-(p)-F, Ph-(p)-Cl, Ph-(o)-F, OC( O)−Ph, and O−Ph) were also investigated. The potential energy barriers of the alkene insertion step are 6.2/8.3, 9.5/5.7, 6.3/10.1, 9.2/10.4, 6.1/8.4, 6.0/9.1, 6.3/9.2, 5.8/7.4, 12.3/9.9, and 9.7/11.5 kcal/mol for Sub1 to Sub10, respectively. R aldehydes are predicted to be dominant except CH2CHC( O)OCH3 (Sub2) and CH2CH−OC(O)−Ph (Sub9), which agree well with experimental results. The calculated results above indicate that the relative stabilities of the coordination modes (A/E mode) of alkene to 2 may play an important role in the enantioselectivity of AHF.

Sub10 are 6.2, 9.5, 6.3, 9.2, 6.1, 6.0, 6.3, 5.8, 12.3, and 9.7 kcal/ mol, respectively. Those along pathway S for Sub1−Sub10 are 8.3, 5.7, 10.1, 10.4, 8.4, 9.1, 9.2, 7.4, 9.9, and 11.5 kcal/mol, respectively. As shown in Table 1, the differences of pathway R over pathway S in the energy barriers are −2.1, 3.8, −3.8, −1.2, −2.3, −1.4, −2.9, −1.6, 2.4, and −1.8 kcal/mol, respectively. The calculated results indicate that the R product is dominant for AHFs of Sub1 to Sub10 except CH2CHC(O)OCH3 (Sub2) and CH2CH−OC(O)−Ph (Sub9). The predicted chirality (R or S) of AHF for Sub1−Sub10 are exactly the same as the experimental results.23,24 The calculated ee values also agree well with corresponding experimental results. The experiment indicated that the final aldehyde products own S conformation in AHFs of vinyl acetate derivatives (CHCH2−OC(O)R) like Sub9.24 This is because intermediate 3R adopts E mode, 3R with A mode was not found in this calculation for Sub9, and 3S adopts A mode. INT 3 with E mode is lower in energy than that with A mode. The polar atoms like N13 and O14 of phosphoramidite moiety of Yanphos ligand may contribute to a strong electrostatic interaction with the carboxyl group of Sub9, which overstabilizes Sub9 with E mode in pathway R1. As a result, the energy barrier from 3 with E mode will spend more energy than that from 3 with A mode to complete the alkene insertion step.45 Therefore, the final chiral product is inverted. At the same time, this study demonstrates that the final aldehyde product should own S conformation in AHF of methacrylate (CH2CH−C(O)OR) like Sub2. The same situation did happen for INT 3 that A mode was not found in pathway R1 yet, which is similar to the alkene insertion step of Sub9. However, the Rh-Yanphos system is predicted not to be suitable for AHF of methyl methacrylate (MAA, CH2 C(CH3)COOCH3), a key intermediate monomer produced on a large scale for the production of poly(methyl methacrylate) (PMMA). This is because AHF of MAA pursue a high l/b ratio instead of a high b/l ratio, and only its linear aldehyde product is chiral. As for CH2CH−C(O)OCH3 and CH2CH−OC( O)−Ph, although there are two regions being sterically large (the third quadrant (III) in pathway R1 and the fourth quadrant (IV) in pathway S2 in Figure 6), these vinyl acetates could form 3R1eq with E mode and extend the chain-like R group on the fourth quadrant (IV). Therefore, pathway S2 is more favored than pathway R1 for Sub2 and Sub9. This might account for the intrinsic nature of the preference of the S product in AHFs of a series of vinyl acetate derivatives.

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ASSOCIATED CONTENT

S Supporting Information *

Imaginary frequencies of transition states, energies, and optimized geometries of all stationary points along reaction pathways. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*(M.L.) Phone: 86-10-6444-6598. Fax: 86-10-6444-6598. Email: [email protected]. 8968



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Notes

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The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was in part supported by the National Natural Science Foundation of China (Grant No. 21373023 and 21072018). We also thank Chemical Grid Project at Beijing University of Chemical Technology (BUCT) for providing a part of the computational resources.

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ABBREVIATIONS: TM, transition metal; TS, transition state; INT, intermediate; TBP, trigonal-bipyramidal; SPy, square-pyramidal; AHF, asymmetric hydroformylation; OXO, hydroformylation; IRC, intrinsic reaction coordinate; A mode, apical coordination mode; E mode, equatorial coordination mode; ee, enantiomic excess

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Asymmetric Hydroformylation Catalyzed by RhH(CO)2[(R,S)-Yanphos

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