Computational Mechanism Study of Catalyst-Dependent Competitive

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A Computational Mechanism Study of Catalyst-Dependent Competitive 1,2-C#C, -O#C, and –N#C Migrations from #-Methylene-#-silyloxy-#amido-#-diazoacetate: Insight into the Origins of Chemoselectivity Xin Yang, Yong-sheng Yang, and Ying Xue ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b02103 • Publication Date (Web): 23 Nov 2015 Downloaded from http://pubs.acs.org on November 23, 2015

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A Computational Mechanism Study of Catalyst-Dependent Competitive 1,2-C→ →C, -O→ →C, and –N→ →C Migrations from

β-Methylene-β-silyloxy-β-amido-α-diazoacetate: Insight into the Origins of Chemoselectivity Xin Yang, Yongsheng Yang, Ying Xue* College of Chemistry, Key Lab of Green Chemistry and Technology in Ministry of Education, Sichuan University, Chengdu 610064, People’s Republic of China

_________________

Corresponding author.

Ying Xue, e-mail: [email protected] Tel: +86 28 85418330.

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Abstract Doyle et al. [J. Am. Chem. Soc., 2013, 135, 1244-1247] recently has reported an efficient catalyst-controlled chemoselectivity of competitive 1,2-C→C, -O→C, and -N→C migrations from β-methylene-β-silyloxy-β-amido-α-diazoacetates using dirhodium or copper catalysts. With the aid of DFT calculations, the present study systematically probed the mechanism of the aforementioned reactions and the origins of the catalyst-controlled chemoselectivity. Similar to the method reported in the literature, simplified catalyst models Rh2(O2CH)4 and Rh2(N-methylformamide)4 have been used in our initial calculations. However, using the model Rh2(O2CH)4 couldn’t describe the energies of all possible pathways and high selectivity of three competitive migrations could not be achieved. In order to appropriately describe this 1,2-migration system, real catalyst models Rh2(cap)4, Rh2(esp)2 and CuPF6 have been employed. It was found that the steric and electronic effects of ligands significantly influence the free energy barrier, which ultimately changes the chemoselectivity. In CuPF6 system, the electronic effects, coupled with the steric factor, give a qualitative explanation for the exclusive chemoselectivity of 1,2-N→C migration over 1,2-C→C or -O→C migration. On the other hand, the bulky ligands of dirhodium catalysts result in the significant steric hindrance around the dirhodium centers and withdrawing the empty space around the bulky group –OTBS. By analyzing the divergence of three different migration transition states using the distortion/interaction and natural bond orbital analyses, it was found that the 1,2-N→C migration will suffer high free energy barrier because of the steric repulsion between the carbonyl group and the carbonyl oxygen of the pyrazolidinone ring. As for 1,2-C→C and -O→C migrations, changing the ligands of dirhodium catalysts can change the electronic properties of carbenes, and that is the reason for controlling the major product by changing the dirhodium catalysts. The mechanistic proposal is supported by the calculated chemoselectivities which are in good agreement with the experimental 2


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results. Keywords: DFT calculations; mechanistic studies; 1,2-migration; metal-carbene; dirhodium catalyst; copper catalyst; chemoselectivity; distortion/interaction analysis.

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1. Introduction 1,2-Migration provides rapid access to complex structures and has been extensively investigated for its intriguing mechanistic features and widespread occurrence in catalysis.1-6 In general, efficient and highly selective migrations can be achieved such as in the semipinacol

rearrangement,7

Wagner-Meerwein

rearrangements,8-13

ring-enlargement

reactions14,15 and gold-catalyzed migrations.16-19 However, although highly selective migrations are most desirable, it is difficult to achieve the desired product when competition between two migrating groups is commonly observed.20 In those reactions, the final product is dependent on the structure of the reactant,9,12,21 and external control of which group migrates

has

long

been

challenging.11,12

Controlling

site

selectivity,

especially

catalyst-controlled migration is rarely encountered,22 and effective catalyst-controlled selectivity is still one of the greatest challenges in these active research field. A new approach to control the site-selectivity from α-diazo carbonyl compounds was recently reported by Doyle and co-workers:23 different metal catalysts direct the migration by carbon, oxygen and nitrogen substituents with a high degree of selectivity to produce a varied array of highly functionalized dinitrogen-fused heterocyclic compounds in a controllable and efficient manner (Scheme 1). Catalytically generated metal carbene intermediates from α-diazo carbonyl compounds are highly electrophilic and directly bonded to a saturated carbon atom having three different substituents. The metal-carbene bearing

β-quaternary carbons can be induced by different catalysts to undergo 1,2-migration of each of the substituents. The selectivity of 1,2-migration is influenced to a considerable extent by the different metal-catalysts (Rh, Cu and Ag) and the stereoelectronic and steric attributes of ligands coordinated to the metal center. They studied a vast array of dirhodium complexes with systematically altering steric and/or stereoelectronic properties. Using the less Lewis acidic Rh2(cap)4 at 80°C showed that both the 1,2-O→C and -N→C migration pathways 4


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were inhibited in favor of the 1,2-C→C migration (entries 4 and 11). The use of Rh2(esp)2 containing sterically bulky ligands revealed that high selectivity for 1,2-O→C migration could be achieved (entry 10) at 40°C. In contrast, silver and copper catalysts displayed characteristic and virtually exclusive selectively for 1,2-N→C migration which couldn’t be detected in reactions catalyzed by dirhodium catalysts (entries 6, 7 and 12). The 1,2-C→C migration (to form 5) and the 1,2-N→C migration (to form 7) pathways were direct competitive using different metal catalysts (Rh and Cu or Ag) with high selectivities, and the 1,2-N→C migration product 7 or 1,2-C→C migration product 5 could be obtained in high yield under catalysis CuPF6 or Rh2(cap)4, respectively. It should be noted that the 1,2-C→C and 1,2-O→C migrations appeared to be linked, but they could be made dominant with a simple change in the ligands attached to the dirhodium centers (entries 10, 11, 13 and 14). The novel template not only successfully achieves the catalyst-controlled highly selective 1,2-migration, but is also able to produce a variety of highly functionalized fused-ring heterocyclic compounds. This work represents a breakthrough in synthetic methodology. However, the mechanism of these transformations and, more importantly, the origins of 1,2-migration selectivity are still unknown. This dramatically hinders the development of this methodology for other catalytically generated metal carbenes. Another key challenge for template design is to understand the fundamental reason of the link between 1,2-C→C and -O→C migrations. Clearly, an essential, molecular-level understanding of this catalyst system is very urgent. Quantum chemical methods have provided insights into the origin of activity and selectivity in the dirhodium-catalyzed reactions.24-33 However, the large size, conformational flexibility and complexity of the dirhodium catalyst make it challenging to carry out meaningful theoretical treatments using realistic structural models, even with modern day computing resources. For such reasons, most of the computational studies in this area have

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been performed using simplified ligand models, such as dirhodium tetraforate Rh2(O2CH)4. Significant insights have been obtained through this approach.8,25,34-40 For example, Davies et. al. examined the reaction between allylic C-H bonds and vinyldiazoacetates (combined C-H activation/Cope rearrangement, CHCR reaction) and concluded that Rh2(O2CH)4 model could be used to explain the experimental selectivity well.41 For the Rh2(S-nap)4-catalyzed intramolecular C-H aminations of 3-phenylpropylsulfamate ester, Zhao et. al. investigated the mechanisms and enantioselectivities in detail with density functional theory (DFT) computations and found that the calculated enantiomeric excess (94.2% ee) was in good agreement with the experimental result (92.0% ee) using simplified catalyst model Rh2(N-methylformamide)4.32 Despite the fact that the use of simplified rhodium model such as Rh2(O2CH)4 is effective in many reactions, there are few studies in which the realistic structural models have been used for Rh catalysts.42-45 For example, a very recent study was performed on the hydroformylation reaction using the actual Rh-catalysts by Kumar et. al.44,45 They revealed that using real catalyst which accounted for nonlocal correlation effects and which allowed for the complete relaxation of the reaction center was important for describing the ligand-based noncovalent interactions which could be crucial in the reaction. Collectively, the present computational work revealed that the issue of 1,2-migration selectivity must be computed in real catalyst models. The traditional dirhodium catalyst model Rh2(O2CH)4 fails to produce the experimental selectivity. In this paper, we have undertaken a detailed computational analysis on this unprecedented 1,2-C→C, -O→C, and -N→C migrations using representative reaction systems. In particular, plausible mechanisms of the reactions have been interrogated by comparing the computed chemoselectivity with the experimental findings. Moreover, using such treatment, key mechanistic questions can be answered: why does copper catalysis display distinctive and virtually exclusive selectivity for 1,2-N→C

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migration? Why do dirhodium catalysts prefer to 1,2-C→C and -O→C migrations rather than 1,2-N→C migration? What is the cause for the 1,2-C→C and -O→C migration link in the dirhodium-catalyzed reaction? What are the fundamental reasons that the ratio of 1,2-C→C and -O→C migration products can be controlled through the ligands on dirhodium catalysts? This manuscript provides additional insight into the 1,2-migration reaction and highlights a compelling evidence that the steric and electronic effects of ligands on dirhodium-catalyzed reactions have a strong influence on the 1,2-migration and therefore should be considered in a proper understanding of experimentally observed ratios. 2. Computational Models In Scheme 1, 1,2-C→C migration product 5b could be obtained in high yield under catalysis of Rh2(cap)4 at 80°C (entry 11), Rh2(esp)2 catalyst could generate 1,2-O→C migration product 6b as major product (entry 10) at 40°C and 1,2-N→C migration product 7b was produced as the exclusive product under the catalysis of CuPF6 (entry 12). In our present studies, the reactions of 3b under those three catalysts (Rh2(cap)4, Rh2(esp)2 (illustrated in Figure 1) and CuPF6) were investigated because the different regioselectivities observed in these reactions make it possible to explore the fundamental mechanism and to test the validity of the mechanism: quantum chemical calculations should not only predict the absolute configuration of the major isomer but also the degree of selectivity observed. Using these models can also explain why certain metal catalysts are highly effective with certain 1,2-migrations but give poor selectivity with others. Our mechanistic studies of the 1,2-migration focus on the catalytic cycle starting from the metal carbene 4b, since previous DFT calculations from Davies39,46 and others8,47,48 have documented the detailed process of Rh(II) and Cu(I) carbene formation from α-diazocarbonyl compounds. Simplified catalyst model: In the initial stage of our calculations, we employed Rh2(formate)4 (Rh2(O2CH)4) and Rh2(N-methylformamide)4 (Figure 1) as the simplified 7


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models for Rh2(esp)2 and Rh2(cap)4 complexes, respectively, in the interest of computational tractability, just like the previous studies in the literature.8,25,32,34-40 These two catalyst models have been widely used and can successfully describe the reaction mechanisms in other systems. Unfortunately, according to our calculations, these simplified catalyst models failed to reproduce the experimental ratios in the 1,2-migration systems (see the discussion part). 3. Computational methods Geometry

optimizations

were

performed

at

the

M06-GD3/BS149

level

in

dichloromethane (the solvent used experimentally) solution using the SMD50,51 (SMD, an IEFPCM (The Polarizable Continuum Model (PCM) using the integral equation formalism variant) calculation with radii and nonelectrostatic terms for Truhlar and co-workers’ SMD solvation model) solvation model with the key word “int=ultrafine”, BS1 designating a mixed basis set of the 1997 Stuttgart relativistic small-core effective core-potential and basis set [Stuttgart RSC 1997ECP]52,53 for Rh, augmented with a 4f-function (ζf(Rh)=1.350),39 and 6-31G(d) for other atoms (C, H, N, O, Cu, P and F). The M06-GD3 functional (D3 version of Grimme’s dispersion with the original D3 damping function) was used due to its superior performance for organometallic systems.54-56 Grimme’s recent studies57,58 have suggested that it is important to include empirically dispersion corrections with these regularly used functionals. This is a refined version of the DFT-D method, DFT-D3, which includes an additional C8/R8 term in the dispersion correction term and takes three-body effects into consideration. This method can lead to better accuracy and transferability because the dispersion coefficients which are calculated using ab initio approach and the cutoff radii are interpolated accounting for the chemical environment of the system. Heavy-atom basis set definitions and corresponding pseudopotential parameters were gained from the EMSL basis set exchange library.59 Frequency outcomes were examined at the same level of theory to confirm stationary

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points as minima (zero imaginary frequencies) or transition states (one imaginary frequency) at the experimental temperature (that is, 40 °C for Rh2(esp)2 and its simplified model Rh2(formate)4, 80 °C for Rh2(cap)4 and its simplified model Rh2(N-methylformamide)4 and 25 °C for CuPF6). All the transition states were further characterized by intrinsic reaction coordinate (IRC) analysis, followed by structure optimization to check that the stationary points were smoothly connected to each other. Single-point energy calculations were carried out for all the M06-GD3/BS1-optimized structures at the M06-GD3/BS2 level with solvation effects modeled by SMD in dichloromethane, BS2 denoting a mixed basis set of the 1997 Stuttgart relativistic small-core effective core-potential and basis set [Stuttgart RSC 1997ECP] for Rh, augmented with a 4f-function (ζf(Rh)=1.350), and 6-311+G(2d,2p) for all other atoms. The thermal corrections evaluated from the unscaled vibrational frequencies at the M06-GD3/BS1 level on the optimized geometries were then added to the M06-GD3/BS2 electronic energies to obtain the free energies using Truhlar’s quasiharmonic approximation.50,60 The chemoselectivity of 1,2-migration was calculated using the following equation, which is based on the relative free energies of the transition states leading to the three different 1,2-migration products: 5b : 6b : 7b = k (5b ) : k (6b) : k (7b ) = exp(-

≠ ≠ ≠ ∆G5b ∆G6b ∆G7b ) : exp() : exp() RT RT RT

(1)

To obtain further insight into the electronic properties of the present system, natural bond orbital (NBO) analyses were performed at the M06-GD3/BS2 level in dichloromethane solution with the SMD model on selected systems. All calculations were performed with Gaussian 09.61 4. Results and Discussion 4.1 Conformational Analysis Considering the vital importance the metal-catalyst conformation can have on the 9


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chemoselectivity outcome of the 1,2-migration reaction, we initiated our study of the metal-carbene conformations by using real catalyst models (Rh2(cap)4, Rh2(esp)2 and CuPF6). We have performed a systematic search for all the minima conformers. Two major factors were considered in a systematic conformational search. As shown in Scheme 2, the first factor is the dihedral angel ψ1, which determines the relative orientations of metal group and the substrate carbonyl oxygen of the pyrazolidinone ring (on the same side of the substrate carbonyl oxygen or on the different sides). The second factor is the dihedral angle ψ2 that determines the position of the ligand on dirhodium-catalyst (Note that only the first factor is considered in CuPF6-carbene in which PF6- is assumed to be a spectator ion, and hence the change of ψ2 is not considered in the calculations). In total, 18 conformers of the metal-carbene minima were located: eight conformation for Rh2(cap)4-carbene; eight conformation for Rh2(esp)2-carbene and two conformation for CuPF6-carbene (See Supporting Information for details). Based on the most stable minima conformers, calculations indicate that among the dirhodium-carbene structures, the carbene Rh2Ln-B, in which the dirhodium-group is far away from the carbonyl oxygen of the pyrazolidinone ring, has a lower energy than that (Rh2Ln-A) with the other orientation. This situation is owing to the lack of steric repulsion between bulky-ligands on dirhodium catalyst and the pyrazolidinone ring in Rh2Ln-B. In contrast, the structure in which the CuPF6 and the carbonyl oxygen of the pyrazolidinone ring are on the same side (CuPF6-A) is energetically favored. This heightened stability for CuPF6-A is due to the interaction of the Cu atom with the carbonyl oxygen of the pyrazolidinone ring (see 4.4 part for detail discussion). Hence, the conformers Rh2(esp)2-B2 and Rh2(cap)4-B1 which own the conformation of Rh2Ln-B, and the conformer CuPF6-A will be chosen as the three representative different meta-carbene models of 1,2-migration to

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investigate the reaction mechanism in the following discussion. 4.2 Simplified Catalyst Model Mechanism. The simplified catalyst model (such as Rh2(O2CH)4) has been shown to be a suitable model for dirhodium carboxylates and was employed as the catalyst for simplicity in the initial to probe possible mechanisms of the 1,2-migration reactions in the interest of computational facility. We first studied the 1,2-migration reactions catalyzed by Rh2(O2CH)4 and Rh2(N-methylformamide)4 which were used to replace the real catalyst models Rh2(esp)2 and

Rh2(cap)4,

respectively.

The

initial

Rh2(O2CH)4-carbene

complex

and

Rh2(N-methylformamide)4-carbene complex adopted the same configurations with Rh2(esp)2-B2 and Rh2(cap)4-B1, respectively. The computed transition structures for three different migrations are illustrated in Figure 2 and 3. From the Rh2(N-methylformamide)4-carbene complex 8, 1,2-C→C migration via TS1 requires an activation barrier of 9.2 kcal/mol with respect to 8. Migration via TS2 gives the 1,2-O→C migration complex 6b with the energy barrier of 12.4 kcal/mol. Meanwhile, the 1,2-N→C migration via TS3 is 2.1 kcal/mol higher than TS2. The calculations indicate a concerted mechanism for three different migrations. The regioisomeric ratio (5b:6b:7b ratio) was estimated using a formula that has been successfully used previously44,45 and that takes into account only the relative energies of the transition states leading to three different migration products (see Computational Method section). The 5b:6b:7b ratio of 98.90:1.04:0.06 for Rh2(N-methylformamide)4-catalyzed migration is agreement with the experimental value of 91:9:- (entry 1, Table 1).When considering the Rh2(O2CH)4-catalyzed migration (Figure 3), the concerted transition structure TS5 for 1,2-O→C migration is 1.0 kcal/mol more stable than the 1,2-N→C migration transition structure TS6, while the 1,2-C→C migration transition state TS4 owns the lowest free energy barrier among these three types of migrations. The 1,2-C→C migration catalyzed by Rh2(O2CH)4 is more 11


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favorable than other two kinds of migrations. However, the difference between those free energy barriers of three different transition states is very small. The migration experimentally yields no 1,2-N→C migration product 7b catalyzed by Rh2(esp)2 and the major product is 1,2-O→C migration product 6b. However, using its simplified model for Rh2(esp)2, the reaction yields three 1,2-migration products in a ratio of 57.4:35.5:7.1 (5b:6b:7b) (entry 2, Table 1) and the catalyst actually couldn’t have the chemoslectivity of three competitive migrations, which is totally disagreement with experimental results. Combining the above two systems, it is obvious that using the simplified model Rh2(N-methylformamide)4 can explain the selectivity in a limited extent, and it is impossible to get the proper results employing the simplified model Rh2(O2CH)4. In summary, the mechanism using simplified models Rh2L4 cannot explain the 1,2-migration regioselectivity observed experimentally very well. Inspired by computational study of the hydroformylation of propene,43 in which the electron and geometric structures of ligand have significant influence on the selectivity, we hypothesized that the bulky-ligands on the dirhodium catalysts may also play a crucial role in understanding regioselectivity. A detailed evaluation of migration reactions catalyzed by real catalyst models rather than the truncated model will be followed. 4.3 Real catalyst models The simplified model catalyst Rh2(O2CH)4 does not offer an explanation for the chemoselectivity of 1,2-migration, since it lacks the bulky ligands present in real catalysts. We have, therefore, performed QM calculations on the 1,2-migration reaction from its real catalyst precursor 4b which specifically refers to the conformer Rh2(esp)2-B2. Besides, we also calculated the chemoselectivities of three competitive migration products using Rh2(cap)4-B1 and CuPF6-A. Structures involved in this process were also optimized in dichloromethane under their own reaction temperatures.

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Similar with previous studies, the 1,2-migrations catalyzed by dirhodium catalysts have been found to proceed through a concerted pathway. For the Rh2(cap)4 catalyst, three transition structures TS7, TS8 and TS9 have been located for three different 1,2-migrations corresponding to 1,2-C→C, -O→C and -N→C migration, respectively (Figure 4). Like in the previous simplified catalyst model, the most stable structure corresponds to 1,2-C→C migration transition structure TS7 forming the product 5b. TS7 is lower by 2.7 kcal/mol than 1,2-O→C migration transition state TS8 in which the –OTBS group transfers to the carbene atom. The Rh2(cap)4-B1 can also undergo 1,2-N→C migration to form product 7b via transition state TS9 with a barrier of 15.9 kcal/mol. When comparing the Rh2(cap)4-catalyzed pathways with its simplified catalyst model catalyzed pathways, the real catalyst model does not change the product trend, as the 1,2-C→C migration product 5b is still predicted to be the dominant product and 1,2-O→C migration could also be observed in the reaction. However, the difference between calculated relative barriers of TS7 and TS8 is lowered by 0.5 kcal/mol using realistic catalyst model Rh2(cap)4, which can lead to a reduction in the ratio of 5b:6b and can be in better agreement with the experimental result. For the Rh2(esp)2 catalyst, the mechanisms of 1,2-migrations are also similar to those using simplified catalyst model. Optimized geometries of transition states involved in three different 1,2-migrations are shown in Figure 5. Unlike in the previous simplified catalyst model, the most stable structure corresponds to 1,2-O→C migration transition structure TS11 in which the bulky phenyl groups parallel to the phenyl ring (R2) in the substrate to avoid steric interactions, and the –COOMe group in the substrate avoids interaction with the carbonyl oxygen of the pyrazolidinone ring. In the 1,2-N→C migration transition structure TS12, this interaction is so important that this structure is destabilized by 1.9 kcal/mol. The formation of the 1,2-C→C migration product is less favorable from the transition state TS10, which has a free energy 0.7 kcal/mol higher than that of the 1,2-O→C migration TS11 13


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structure. When comparing the Rh2(esp)2-catalyzed pathways with its simplified catalyst model-catalyzed pathways, the sequence of free energy barriers for three types of migrations are totally different with each other and using the real catalyst model does change the product trend, as the 1,2-O→C migration product 6b is predicted to be the dominant product and the alternative mechanism through 1,2-C→C is closely competitive. These finds are in good agreement with the experimental results These calculated energy differences can be used to calculate the isomeric excesses that should be expected in these reactions. Using the Rh2(cap)4 catalyst, the 5b:6b:7b ratio was reported to be 91:9:- at 80 °C in the literature. Our calculation suggests a value of 97.8:2.1:0.1 ratio for this temperature (entry 3, Table 1). The Rh2(esp)2 catalyst gives 15:85:ratio of 5b:6b:7b at 40 °C experimentally, and the present calculation suggests a value of 23.7 : 73.0 : 3.3 (entry 4, Table 1) for this temperature. Both of these calculated values are close to the experimental ones, and the relative efficacy of the two catalysts is reproduced very well. A better correction between the experimental value and the results of our calculations could be rooted in the fact that the geometry optimization of the transition states and the minima has been wholly performed at the QM level that provides an authentic description of ligand correction effects. The mechanistic study shows that the bulky ligand in dirhodium catalyst is needed, and we will discuss the structures of the regioisomeric transition states and the fundamental reasons of selectivity in more detail later. In the experiment, CuPF6 is found to be an effective catalyst for the 1,2-N→C migration reaction. Three 1,2-migration pathways have been investigated with computations, and the optimized geometries and free energies are illustrated in Figure 6. These energies are with respect to the resting state, CuPF6-carbene CuPF6-A. 1,2-C→C migration could take place over a concerted transition state TS13 that was confirmed by IRC analysis. Another possible pathway leading to the product 6b is 1,2-O→C migration with the transition state TS14 to 14


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regenerate the active catalyst CuPF6. The free energy barrier of TS14 is higher than that of TS13 in 1,2-C→C migration path by 0.1 kcal/mol. Meanwhile, 1,2-N→C migration leading to the product 7b proceeds with migration of group –OTBS via TS15. The 1,2-N→C migration is kinetically much more favorable than 1,2-C→C or 1,2-O→C migration by at least 4.5 kcal/mol. Thus, there is an overwhelming preference for 7b over 6b or 5b, which explains why the typical 1,2-C→C migration product 5b and 1,2-O→C migration product 6b were not observed experimentally (entry 5, Table 1). We will next discuss the origins of virtually exclusive selectivity for 1,2-N→C migration catalyzed by copper complex by examining the structures of the key transition states and intermediates. 4.4 Explanations for the chemoselectivity for 1,2-N→ →C migration catalyzed by copper complex Although 1,2-migration catalyzed by CuPF6 has three possible pathways that could engage in three different products, the reaction occurs exclusively with 1,2-N→C migration. In order to understand the origin of chemoselectivity, we analyzed, in several ways, the nature molecular orbitals in CuPF6-A and three migration transition states TS13, TS14 and TS15. The 3-D structure and Important molecular orbitals of the CuPF6-carbene CuPF6-A are shown in Figure 7. The important issue to be addressed here is the influence of the -C=O group of the pyrazolidinone ring on the character of the Cu-C4 bond system. In this structure, the -C=O group of the pyrazolidinone ring and the C-Cu bond are considered to have some interaction. Indeed, one can identify HOMO-8 of CuPF6-A (Figure 7b) that illustrates interaction between the Cu 3dz2 orbital with –C=O group of the pyrazolidinone ring. In addition, there is another distinct interaction in CuPF6-A complex. HOMO-9 (Figure 7c) illustrates donation from the nonbonding oxygen 2p orbital to the empty orbital of the Cu atom. On the other hand, no donation from the -C=O group of the pyrazolidinone ring to the Cu 4d-orbital was identified in CuPF6-B complex. This indicates that the 4d orbital of the 15


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Cu is subject to back-donation from oxygen atom of the pyrazolidinone ring, as well as back-donation from the carbene atom in conformer CuPF6-A. Thus, the -C=O group of the pyrazolidinone ring affects the character of the C-Cu system. This donation not only affects the relative stability of the different CuPF6-carbene conformers, but also is an important driving force of the 1,2-N→C migration. The computed chemoselectivity is in good accord with experiment. We herein examine the structures of diastereomeric TS13, TS14 and TS15 (Figure 6) to understand their difference in energy, from which the chemoselectivity originates favoring the 1,2-N→C migration over 1,2-C→C or 1,2-O→C migration. In TS15, the phenyl groups R1 and R2 are parallel to each other, whereas this relative position is not the case in TS13 and TS14. The orientation of phenyl group R2 toward the other phenyl group R1 is crucial because it brings significant π/π attractive dispersion forces in TS15. In fact, this kind of π/π interaction has been acknowledged previously by numerous computation investigations as a differentiating factor for the energy of optimized geometries.62-64 Interaction of the π-bonding orbital of phenyl group R2 with that of phenyl group R1 can be identified in the HOMO-2 shown in Figure 8a. Furthermore, in TS14 the bulky substituent –OTBS points in a very close direction to Cu atom, thereby strong H⋅⋅⋅Cu steric repulsion occurs in TS14 than TS15, as indicated by comparing the two sets of shortest nonbonding H⋅⋅⋅Cu distances. We have discussed the donation of the carbonyl oxygen of the pyrazolidinone ring to Cu 3d/4d orbital that leads to the CuPF6-carbene complex CuPF6-A in preference to the complex CuPF6-B, which is primarily thermodynamic because this donation in CuPF6-A makes it more stable than the complex CuPF6-B. Such donation also can be clearly identified in the orbitals of TS13, TS14 and TS15 (Here we only list the HOMO orbitals (Figure 8b, c, d) for those three transition states. For other orbitals illustrating the interaction between -C=O group of the pyrazolidinone ring and the C-Cu bond have been shown in 16


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Figure S4 in the Supporting Information). However, TS15 has a stronger donation than TS13 or TS14. Nonetheless, this donation effect alone seems insufficient to explain the difference of ca. 4.5 kcal/mol in energy between TS15 and TS13 or TS14. Thus, we calculated NBO charges of key structures to investigate bond polarities and their influence on the 1,2-migration reactions (Figure 9). The NBO charges suggest that the C4(carbene atom)-N7 Coulombic repulsions in CuPF6-A and TS15 would be weaker than C4-O6 or C4-C5 Coulombic repulsion. The electrophilic Cu atom coordinated to the carbene polarizes the Cα-Cβ bond, making Cα more positively charged, and this is corroborated by the NBO charge analysis of the 3b in isolated, unbound condition (Figure 9). In order to obtain more insights into the fundamental factors that control the activation barriers of the 1,2-migration catalyzed by CuPF6, a distortion/interaction analysis65-77 was performed for the key transition structures to quantify different contributions to the 1,2-migration barrier. This analysis which is also called as the activation-strain model,78-81 has been applied to elucidate the reactivates and selectivities in different systems including the transition metal catalysis.65-81 In bimolecular reaction, the activation barrier (∆E≠) can be decomposed into two contributions: the distortion (or strain) energy ∆Edist which is associated with the distortion of the reactants from their equilibrium structures to their geometries in the TS structure, plus the interaction energy (∆Eint) between the deformed reactants. Although the 1,2-migration from reactant complex CuPF6-A is not a bimolecular reaction, the distortion/interaction model can be still analyzed here to show the difference between TS13, TS14 and TS15 by using complex CuPF6-A as a reference, as suggested by Bickelhaupt and Fernández82 (This method has also been successfully employed on another unimolecular system recently.83 As illustrated in Table 2 (entries 1-3), the energies for distortion of the CuPF6 moiety (∆Edist(M)) are very similar in TS13, TS14 and TS15. Thus, the distortion of the catalyst CuPF6 does not noticeably affect the chemoselectivities of 17


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1,2-migration. The energy required to distort the carbene substrate into the transition state geometry (∆Edist(carbene)) shows a big difference. ∆Edist(carbene) of TS15 is 0.4 kcal/mol higher than that in TS14, and TS13 owns the lowest ∆Edist(carbene). The distortion energy (∆Edist) does not correlate well with the activation energy, which indicates that substrate distortion is not the major factor controlling the chemoselectivities. Actually, these compounds have large differences in the interaction energy ∆Eint. 1,2-N→C migration TS15 owns the significantly lowest ∆Eint which favors the regioisomeric transition state and leads to the observed exclusive product. This results again indicate that the interaction of the Cu atom with the carbonyl oxygen of the pyrazolidinone ring play a key role in the CuPF6-catalyzed 1,2-migration. Therefore, the electronic effects, coupled with the aforementioned steric factor, give a qualitative explanation for the difference in energy among TS13, TS14 and TS15, and the exclusive chemoselectivity that favors 1,2-N→C migration over 1,2-C→C or 1,2-O→C migration. 4.5 Origins of the link between 1,2-C→ →C and -O→ →C migrations and their selectivities in dirhodium-catalyzed mechanisms. The explorations of the reaction mechanisms catalyzed by Rh2(esp)2 and Rh2(cap)4 suggest that the 1,2-N→C migration mechanism can be excluded due to its relative high free energy barrier. On the other hand, the link between 1,2-C→C and -O→C migrations has been observed in those two reactions, and the major isomer can be controlled. We herein examine the structures of dirhodium-carbene and diastereomeric transition states to understand their energy difference. Calculated bond distances for Rh2(esp)2-B2 and Rh2(cap)4-B1 show that the Rh8-C4 and Rh8-Rh9 bonds in Rh2(cap)4-B1 are longer by 0.061 Å (2.016 Å vs 1.955 Å) and 0.016 Å (2.471 Å vs 2.455 Å) than those in Rh2(esp)2-B2, respectively. This indicates that the Rh8-C4 bond in Rh2(cap)4-B1 has weaker single bond character compared with that in Rh2(esp)2-B2. The longer Rh8-Rh9 bond of 2.471 Å 18


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indicates a weaker metal-metal interaction, therefore the interaction between the two dirhodium atoms should be enhanced by the two ligands, which in turn supports the significant spin density delocalization over the two ligands in Rh2(esp)2-B2. To obtain a more detail qualitative description of the Rh8-C4 character, we further visualized the molecular orbitals (Figure 10). The Rh9 nonbonding 4dz2 orbital interacts with the Rh8-C4 σ/σ*-orbitals, which weakens the Rh8-C4 σ-bond. This interaction is important in the 1,2-migration reaction, where Rh8 moves toward Rh9, and the Rh8-C4 bond is being cleaved as the migration proceeds. On the other hand, the nonbonding carbene C4 2sp orbital interacts with the Rh8-Rh9 σ/σ*-orbitals. Those interactions form the orbital interaction HOMO-2, HOMO-4 (Figure 10a, b), and LUMO+2 (not shown). With this interaction the Rh8-Rh9 bond weakens, and negative charge moves from the carbene atom to the Rh8 atom. In Rh2(cap)4-B1, the Rh9 4dz2 orbital interacts with the Rh8-C4 σ/σ*-orbitals, which can weaken the Rh8-C4 σ-bond (Figure 11a and 11b). This interaction is an important driving force to remove Rh2Ln in the transition state as the 1,2-migration proceeds when Rh8 moves toward Rh9 or to enhance the electrophilicity of the carbene center when Rh8 detaches from Rh9 (charge transfer occurs from the carbene atom to the Rh8 atom and a formal cationic Rh9-carbene complex is formed). The orbital interactions between the strongly donating caprolactamate groups and dirhodium centers increase the capacity of the dirhodium centers to back-donate to the carbene moiety, therefore the carbene atom in Rh2(cap)4-B1 holds higher electronic density than Rh2(esp)2-B2 and acts as a weaker electrophile. The calculated chemoselectivities shown above indicate that, in the copper-catalyzed pathway, the coordination of the copper center with the carbonyl oxygen of the pyrazolidinone ring is vitally important to the exclusive selectivity for 1,2-N→C migration. While in the dirhodium-promoted reactions, the metal and the carbonyl oxygen of the pyrazolidinone ring are positioned on different side. Geometries of the transition states 19


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involving dirhodium catalysts are shown in Figure 4 and 5. In Rh2(esp)2-system, the TS11 is the most stable transition structure among these three transition states. The 1,2-N→C migration (TS12) is 1.9 kcal/mol less stable than TS11. Like the discussion we have made before, the optimized structure of TS12 is significantly different from TS10 and TS11. In TS12, the carbonyl group attached with carbene atom lies close to the carbonyl oxygen of the pyrazolidinone ring to increase the steric repulsion. On the other hand, the steric bulkiness of the ligand groups might influence both the steric and electronic effects of 1,2-migration transition state. From electronic effect, it leads to a more electron-deficient (compared with the simplified catalyst model Rh2(O2CH)4) Rh(II) center due to the truncation of the ligands and thus disfavors the 1,2-N→C migration process (requires the d→π* back-donation interaction from Rh to carbene atom). From steric effect, it results in the significant steric hindrance around the dirhodium centers, withdrawing the empty space around the bulky group –OTBS and making the Rh2L2 coordination atmosphere bulky. The TS12 is destabilized by strong steric repulsion between the R1 group and the ligand on the catalyst: one of the H atoms on the R1 group (Ph group) points to one of the H atoms on the ligand at a distance of 1.94 Å, which is not expected on the simplified catalyst model Rh2(O2CH)4. To provide additional insight into the origin of the regioselectivity of 1,2-migration catalyzed by Rh2(esp)2, distortion/interaction and NBO analyses were carried out. As shown in Table 2 (entries 4-6), the 1,2-N→C migration transition state TS12 owns the highest distortion energy of Rh2(esp)2 moiety, 0.8 kcal/mol higher than 1,2-O→C migration transition state TS11. Besides, the stronger steric effect arising from the carbene moiety also contributes to greatest distortion of carbene (∆Edist(carbene)) in TS12. The total distortion energy required for TS12 is ca. 3.4 kcal.mol higher than that for 1,2-O→C migration transition state TS11, which is agreement with the optimized geometries obtained from DFT 20


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calculations. To achieve the 1,2-N→C migration would suffer from unfavorable steric interaction, which is the cause of the regioselectivity. Compared with 1,2-C→C migration transition state TS10, the 1,2-O→C migration transition state TS11 is favored as its distortion energy is 1.2 kcal/mol lower than TS10. NBO calculations (Figure 12) show that the populations of migration atoms C5 and O6 are similar with each other (C5 owns negative charge of -0.392 in TS10; and O6 owns negative charge of -0.759 in TS11), while the populations of carbene atom C4 are reverse (C4 atom in TS10 owns negative charge of -0.045; but in TS11, C4 atom owns positive charge of 0.074). The electron interaction in TS11 would be more advantageous than that in TS10, which can lead to a slight lower activation free energy barrier in TS11. These results demonstrate that the major 1,2-O→C migration product can be formed, even though the 1,2-C→C and -O→C migrations are linked with each other in Rh2(esp)2-catalyzed reaction. That this 1,2-migration reaction catalyzed by Rh2(esp)2 disfavors 1,2-N→C migration is attribute to the gap (at least 1.2 kcal/mol) between TS12 and TS10 or TS11, which gives a calculated 1,2-C→C and -O→C migrations selectivity of 96.7% that is consistent with the experimental results. We have explained above why the 1,2-N→C migration is disfavored over another two 1,2-migrations and why the 1,2-C→C and -O→C migrations are linked with each other catalyzed by Rh2(esp)2, and this chemoselectivity results from a combination of electronic and steric effects. Similar structural factors appear to set apart TS9 and TS7 or TS8 energetically in Rh2(cap)4-system. To elucidate whether the electronic effect makes an important contribution to the consistent chemoselectivity using real catalyst model Rh2(cap)4 or not, we carried out the following analysis. In one hand, the NBO charge analysis on three different 1,2-migration transition states and their reactive precursor (Figure 13) indicates that the value of the positive charge on Rh8 21


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atom using real catalyst model is slightly larger than that in corresponding transition states and reactive precursor using simplified catalyst model, and using the simplified catalyst model can lead to a little higher electron density on carbene atom C4. However, the change of the NBO charge from the reactive precursor to the 1,2-migration transition state is almost the same using real and simplified catalyst models and the electronic effects of real and simplified ligands do not show significant difference, which leads to only slight difference on the activation free energy barrier. For example, the NBO charges of the β-quaternary carbon atom C3 vary from 0.450 (in Rh2(N-methylformamide)4-carbene 8) to 0.613 (in 1,2-C→C migration transition state TS1) and the difference of the C3 atom NBO charges on 1,2-C→C migration pathway (Rh2(cap)4-B1 and TS7) is 0.179 using real catalyst model. The corresponding free energy barriers are 11.0 kcal/mol and 9.2 kcal/mol, respectively, which are similar with each other. Therefore, N-methylformamide and caprolactamate groups show similar electronic effects, and the chemoselectivity of competitive 1,2-C→C, -O→C, and -N→C migrations is very close, which is consistent with the results above. On the other hand, the optimized structures using simplified catalyst model (i.e, the configurations of carbenes and 1,2-migration transition states in Figure 2 ) are quite close to those using real catalyst model (Figure 4). All of these analyses suggest that using simplified and real ligands can have few difference on the electronic and steric effects, but those effects can significant affect the 1,2-C→C migration selectivity from the 1,2-O→C and -N→C migrations. In this context, the 1,2-N→C migration becomes more disfavored (with an extra free energy barrier of ca. 2.1 kcal/mol), and the 1,2-C→C and -O→C coupling products are obtained with a slightly high yield of 1,2-C→C migration product 5b. Even though we can successfully explore the effect of simply and real catalyst ligands and the reason of the disfavored 1,2-N→C migration pathway using NBO analysis, the straightforward factor to distinguish the 1,2-C→C and -O→C migration pathways is needed to describe the origins of 22


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reactivities and regioselectivities. We performed the distortion/interaction analysis on these three transition states. The result from distortion/interaction analysis mirrors those from DFT analysis and suggests that a more subtle effect could be operative. As illustrated in Table 2 (entries 7-9), the energy for distortion of the Rh2(cap)4 moiety (∆Edist(M)) in 1,2-N→C migration transition state TS9 is much larger than that in other two transition states TS7 and TS8, which leads to the highest distortion energy (∆Edist) TS9. This is corresponding to the relatively large deformation for the Rh2(cap)4-carbene in TS9 because of the steric effect between the ligands on Rh2(cap)4 and the carbene group. In the case of 1,2-C→C and -O→C migration, both the catalyst moiety and the carbene moiety are more distorted in 1,2-O→C migration transition state TS8 than in 1,2-C→C migration transition state TS7. The latter TS is favored as its total distortion energy is 2.2 kcal/mol lower than the former one, implying that substrate distortion is the major factor that results in the observed 1,2-C→C migration major product. In conclusion, computational investigations have shed light on the mechanistic pathways of metal-catalyzed 1,2-migration reactions. Our computational results successfully explain the disfavored direction of the 1,2-N→C migration and the fundamental reason for the link between 1,2-C→C and -O→C migration. In addition, our results explain the observed result that the major migration product can be controlled by changing the ligands on dirhodium catalysts. 5. Conclusion Metal-catalyzed chemoselective α-diazoacetates 1,2-migration reactions is a powerful strategy for the preparation of highly functionalized dinitrogen-fused heterocyclic compounds. To figure out the fundamental reasons of this intriguing chemoselectivity, we conducted a DFT study on 1,2-migration reactions from β-methylene-β-silyloxy-

β-amido-α-diazoacetates catalyzed by simplified and real catalyst models and gain the 23


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following conclusions. The present studies have revealed, for the first time, the energies, the electronic properties, the 3-D structures of the reactive precursors and the TSs in the 1,2-migration reactions catalyzed by dirhodium and copper complexes. Some pertinent experimental results have been reasonably reproduced by the DFT calculations using the realistic structural models for catalysts, that is, the distinctive and virtually exclusive selectivity for 1,2-N→C migration catalyzed by copper catalysis, the link between 1,2-C→C and -O→C migrations when the reaction catalyzed by dirhodium complexes, and the experimental chemoselectivities of competitive three different migrations. The calculations indicate the coordination of the copper atom with the carbonyl oxygen of the pyrazolidinone ring mainly leads that the copper-carbene 4 prefers to be CuPF6-A rather than CuPF6-B in which the Cu-group is too far away from the carbonyl oxygen of the pyrazolidinone ring to have any interaction. On the other hand, Rh2Ln-B conformation is more favored than Rh2Ln-A due to the steric effect and the absence of the donation to metal atom from the carbonyl oxygen of the pyrazolidinone. Meantime, the comparative analyses of the optimized TSs geometries as well as of the chemoselectivities for the 1,2-migration reactions of the Rh2Ln catalyst with and without bulky-ligands imply that the electronic and steric effects from the ligands play a key role in governing the chemoselectivity. Additional calculations involving the molecular orbital, distortion/interaction and NBO analyses further imply that these effects and noncovalent

interaction

contribute

significantly

toward

the

chemoselectivity

of

1,2-migration. The above mechanisms could well explain the experimental observations. The calculated isomeric excess catalyzed by CuPF6, Rh2(esp)2 and Rh2(cap)4 are in excellent agreement with the experimental results. On this basis, it was found that the widely used simplified dirhodium catalysts model Rh2(O2CH)4 could not perform well in the

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α-diazoacetates 1,2-migration systems even though it can successfully describe the reaction mechanisms in other similar systems. The result highlights the subtle effect the ligand has on the carbene intermediates, and thereby plays an influential role in the regiochemical outcome of the 1,2-migration reaction. In order to get quantitative results, the effect of the ligands on Rh2Ln catalysts which provide steric effect and/or electronic effect, must be considered. Therefore, it should be very careful when using the truncated Rh2Ln catalyst models in the calculations. These theoretical results presented here will be helpful in understanding other migration reactions in a wide range of substrates and could be used to guide both ligand and experimental design to optimize the chemoselectivity of metal-catalyzed 1,2-migration reaction. Further theoretical and experimental studies of chemoselective 1,2-migration reactions catalyzed by other metal catalysts are in progress. ASSOCIATED CONTENT Supporting Information

Additional computation results. This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Authors [email protected] Notes The authors declare no competing financial interest

ACKNOWLEDGMENT This project has been supported by the National Natural Science Foundation of China (Grant Nos. 21573153 and 21173151).

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Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision D.01; Gaussian, Inc., Wallingford, CT, 2009. (62) Tsuzuki, S.; Honda, K.; Uchimaru, T.; Mikami, M.; Tanabe, K. J. Am. Chem. Soc. 2002, 124, 104–112. (63) Gignone, A.; Piane, M. D.; Corno,M.; Ugliengo, P.; Onida, B. J. Phys. Chem. C 2015, 119 , 13068–13079. (64) Medveď, M.; Budzák, Š.; Laurent, A. D.; Jacquemin, D. J. Phys. Chem. A 2015, 119, 3112−3124 (65) Ess, D. H.; Houk, K. N. J. Am. Chem. Soc. 2007, 129, 10646−10647. (66)Legault, C. Y.; Garcia, Y.; Merlic, C. A.; Houk, K. N. J. Am. Chem. Soc. 2007, 129, 12664−12665. (67) Ess, D. H.; Houk, K. N. J. Am. Chem. Soc. 2008, 130, 10187−10198. (68) Hayden, A. E.; Houk, K. N. J. Am. Chem. Soc. 2009, 131, 4084−4089. (69) Belding, L.; Taimoory, S. M.; Dudding, T. ACS Catal. 2015, 5, 343–349 (70) Liang, Y.; Mackey, J. L.; Lopez, S. A.; Liu, F.; Houk, K. N. J. Am. Chem. Soc. 2012, 134, 17904−17907.

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ACS Catalysis

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Entry

Catalyst

1

Rh2(N-methylformamide)4

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∆∆G≠

∆∆G≠

∆∆G≠

(5b)

(6b)

(7b)

0

3.2

Ratio

Ratio

(5b:6b:7b)

(5b:6b:7b)

computed

experimental

5.3

98.9:1.04:0.06

91:9:-

2

Rh2(O2CH)4

0

0.3

1.3

57.4:35.5:7.1

15:85:-

3

Rh2(cap)4

0

2.7

4.9

97.8:2.1:0.1

91:9:-

4

Rh2(esp)2

0

-0.7

1.2

23.7:73.0:3.3

15:85:-

5

CuPF6

0

0.1

-4.5

-:-:100

-:-:100

Table 1. Relative free energies (kcal/mol) and product ratio of 1,2-migration reactions catalyzed by simple and real catalyst models.

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ACS Catalysis

∆E≠

Entry

Transition State

1

TS13

5.4

0.3

3.2

3.5

1.9

2

TS14

6.6

0.5

3.9

4.4

2.2

3

TS15

2.3

0.8

4.3

5.1

-2.8

4

TS10

5.5

1.2

4.1

5.3

0.2

5

TS11

4.7

2.0

2.1

4.1

0.6

6

TS12

8.9

2.1

5.4

7.5

1.4

7

TS7

9.3

1.1

4.1

5.2

4.1

8

TS8

13.4

1.5

5.5

7.0

6.4

9

TS9

16.7

3.4

6.7

10.1

6.6

∆Edist(M)

∆Edist(carbene)

Table 2. Distortion/interaction analysis of key transition states.

33


∆Edist

∆Eint

ACS Catalysis

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Scheme 1. Strategy for the synthesis of α-diazoacetates bearing β-quaternary carbons and catalyst screening for the chemoselectivity of competitive 1,2-C→C, -O→C, and -N→C migrations.

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ACS Catalysis

Scheme 2. Conformations of dirhodium-carbenes involved in the 1,2-migration reactions ((a) Metal group (red) and the substrate carbonyl oxygen of the pyrazolidinone ring (green) are positioned on the same side. (b) Metal group and the substrate carbonyl oxygen of the pyrazolidinone ring are on different side).

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ACS Catalysis

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 1. Two real catalysts, Rh2(esp)2 and Rh2(cap)4, involved in the present paper, and their simplified catalyst models.

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ACS Catalysis

Figure 2. Optimized structures and free energy barriers (kcal/mol) of Rh2(N-methylformamide)4-catalyzed 1,2-migration reaction with selected bond distances given in angstroms.

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ACS Catalysis

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Figure 3. Optimized structures and free energy barriers (kcal/mol) of Rh2(O2CH)4-catalyzed 1,2-migration reaction with selected bond distances given in angstroms.

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ACS Catalysis

Figure 4. Optimized structures and free energy barriers (kcal/mol) of Rh2(cap)4-catalyzed 1,2-migration reaction with selected bond distances given in angstroms.

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ACS Catalysis

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Figure 5. Optimized structures and free energy barriers (kcal/mol) of Rh2(esp)2-catalyzed 1,2-migration reaction with selected bond distances given in angstroms.

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ACS Catalysis

Figure 6. Optimized structures and free energy barriers (kcal/mol) of CuPF6-catalyzed 1,2-migration reaction with selected bond distances given in angstroms.

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ACS Catalysis

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Figure 7. (a) Optimized geometry and important molecular orbital interactions involved in the complex CuPF6-A (b, HOMO-8 and c, HOMO-9).

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ACS Catalysis

Figure 8. Important molecular orbital interactions involved in CuPF6-catalyzed 1,2-migration transition states: (a) HOMO-2 of TS15; (b) HOMO of TS13; (c) HOMO of TS14; (d) HOMO of TS15.

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ACS Catalysis

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Figure 9. NBO charge on three 1,2-migration transition states catalyzed by CuPF6 and their precursor CuPF6-A.

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ACS Catalysis

Figure 10. Important molecular orbitals of Rh2(esp)2-B2 (a, HOMO-2; and b, HOMO-4).

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ACS Catalysis

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Figure 11. Important molecular orbitals of Rh2(cap)4-B1 (a, HOMO-2; and b, HOMO-3).

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ACS Catalysis

Figure 12. NBO charge for (a) 1,2-C→C migration transition sate TS10 and (b) 1,2-O→C migration transition sate TS11.

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ACS Catalysis

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Figure 13. NBO charge on three 1,2-migration reactions catalyzed by Rh2(cap)4 and its simplified catalyst model Rh2(N-methylformamide)4.

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ACS Catalysis

TOC

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Computational Mechanism Study of Catalyst-Dependent Competitive

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