Theoretical Study of Ruthenium(0)-Catalyzed Transfer Hydrogenative

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Theoretical Study of Ruthenium(0)-Catalyzed Transfer Hydrogenative Cycloaddition of Cyclohexadiene and Norbornadiene with 1,2-Diols to Form Bridged Carbocycles Tian Zhang, Ting Li, Xiajun Wu, and Juan Li J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03276 • Publication Date (Web): 18 Feb 2019 Downloaded from http://pubs.acs.org on February 19, 2019

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The Journal of Organic Chemistry

Theoretical Study of Ruthenium(0)-Catalyzed Transfer Hydrogenative Cycloaddition of Cyclohexadiene and Norbornadiene with 1,2-Diols to Form Bridged Carbocycles Tian Zhang, Ting Li, Xiajun Wu and Juan Li*

Department of Chemistry, Jinan University, Huangpu Road West 601, Guangzhou, Guangdong 510632, P. R. China

*Corresponding author. E-mail: [email protected] (J. Li) RuLn

Ru0

Ru0

O O

3,5-Me2BzOH

OH OH

exo- and diastereoselectivity HO

OH

DFT Calculations RuLn

Ru0

O O

HO

OH

exo- and diastereoselectivity

ABSTRACT The recent success of Krische et al. (Angew. Chem., Int. Ed. 2017, 56, 14667–14671)

in

achieving

ruthenium(0)-catalyzed

transfer

hydrogenative

cycloaddition of 1,2-diols with cyclohexadiene and norbornadiene in excellent yield with exo- and diastereoselectivity represents an exciting development in synthesis of bridged carbocycles. In the present work, the possible catalytic mechanisms and origin of the exo- and diastereoselectivity for cyclohexadiene and norbornadiene were 1

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studied in detail by density functional theory calculations. The theoretical results indicate that the exo-selective pathway for cyclohexadiene substrate proceeds by novel two-step successive C–C coupling, while the endo-selective pathway undergoes the C–C coupling reaction in a conventional concerted manner. The origin of the preferential

chemoselectivity

of

dione–cyclohexadiene

C–C

coupling

over

aromatization to benzene was investigated. Aromatization to benzene is unfavorable because of the large distortion energy of the three-membered ring in the transition state of hydrogen migration. From distortion/interaction analysis, for norbornadiene, the distortion energy plays the main role in determining the exo-selectivity.

1. INTRODUCTION Bridged carbocycle systems, including bridged bicyclic and tricyclic carbocycles, are ubiquitous in numerous families of biologically active natural products and unnatural bioactive compounds because of their versatile reactivity.1 Efficient construction of bridged carbocycles has therefore attracted considerable interest from synthetic chemists, and it has prompted the development of numerous synthetic strategies.2 Since the advent of photocycloaddition (1908)3 and the Diels–Alder reaction (1928),4

various metal-catalyzed cycloaddition reactions have been

developed. Transition-metal-catalyzed cycloadditions5 are among the most important methods

for

construction

of

complex

ring

systems.

Catalytic

hydrogen-transfer-mediated cycloaddition, which can convert lower alcohols to higher alcohols,6 is a broad area of research. Diols are of interest for biomass 2


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conversion7 and they are important intermediates or terminal structural elements in many syntheses.8 A wide range of diols have been found to participate in metal-catalyzed hydrogen transfer to π-unsaturated reactants.9-11 Hydrogen exchange to promote C–C coupling between diols and dienes has been achieved using ruthenium(0) catalysts. Although exceptions exist,10d the substrate scope is generally restricted to acyclic dienes.10 C–C bond-formation hydrogen transfer reactions of diols with cyclic dienes, such as cyclohexadiene or norbornadiene, is still difficult because competing aromatization (cyclohexadiene to benzene) and catalyst deactivation decrease the feasibility of such processes. Krische et al.11 recently reported phosphine-modified zero-valent ruthenium complexes catalyzed

transfer

hydrogenative

cycloaddition

of

cyclohexadiene

2a

and

norbornadiene 2b with 1,2-diols 1 to form bridged carbocycles (Scheme 1). One of the key aspects of their results is that novel bridged bicyclic ring systems are accessible from diols with good yield and complete control of the exo- and diastereoselectivity. Experiments also showed that the reactivity of the C–C bond-formation hydrogen transfer reactions between 2a and 1 is greatly affected by the 3,5-dimethylbenzoic acid (3,5-Me2BzOH) additive. The aim of this study is to determine plausible explanations to some of the mechanistic issues of Ru3(CO)12-catalyzed transfer hydrogenative cycloaddition: (1) Why is C–C bond-formation hydrogen transfer favored over aromatization when cyclohexadiene is the substrate? (2) What factors control the exo- and diastereoselectivity of the reaction? (3) Why does introduction of a carboxylic acid 3



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additive into the reaction system result in a significant increase in the yield? What is the role of the 3,5-Me2BzOH additive? (4) Do conjugated and non-conjugated dienes have different reaction pathways? To investigate these issues, we performed density functional theory (DFT) calculations. We expect that this study will help experimentalists to perform more challenging metal-catalyzed transfer hydrogenative cycloadditions. Scheme 1. Ruthenium(0)-Catalyzed Transfer Hydrogenative Cycloaddition 2a

HO

OH

Ru3(CO)12 dppe PhMe

3,5-Me2BzOH 140 °C

1

+

OH OH

HO HO

3a endo 3a:3a >20:1

3a exo

2b 130 °C

HO

OH

3b exo

+

HO

OH

3b endo 3b:3b >20:1

2. COMPUTATIONAL DETAILS All of the calculations were performed with the Gaussian 09 program.12 The geometries of all of the species were fully optimized in the solvent phase by DFT with the B3LYP functional.13 In these calculations, the Ru atom was described by the LANL2DZ basis set, including a double-valence basis set with the Hay and Wadt effective core potential.14 Polarization functions were added for Ru (f = 1.235).15 The 6-311G*16 basis set was used for the other atoms. Frequency calculations were also performed at the same level of theory to identify all of the stationary points as minima (zero imaginary frequencies) or transition states (one imaginary frequency), and to calculate the free energies. The connections between the key transition-state structures and the corresponding reactants and products were confirmed by intrinsic 4


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reaction coordinate calculations.17 The solvent effect was considered with the SMD solvation model18 using toluene as the solvent. To acquire more accurate energy information, all of the energies were corrected by single-point calculations at the M06 level.19 In the single-point energy calculations, the def2-TZVP20 basis set was used for Ru and the 6-311++G** basis set was used for all of the other atoms. We also performed single-point energy calculations using the DFT-D3 empirical dispersion correction reported by Grimme et al.21 3. RESULTS AND DISCUSSION Scheme 2 outlines the reaction sequence, including four stages: transformation of diol

1

to

ketol

1′,

transformation

of

ketol

1′

to

dione

1′′,

dione–cyclohexadiene/norbornadiene C–C coupling, and protonation leading to final product 3a or 3b. We detail below the mechanism of the reaction in terms of the four stages. Scheme 2. Sequence of Reaction in Scheme 1. O

HO Ph2P OC

Ru

PPh2

Ph2P

Ru

CO RuLn

CO RuLn

4 RuLn

OH

RuLn

O

RuLn

O

O

1 OH OH

O O

OH

2b

2b

RuLn

O O

1

2b O O RuLn

1 2b

O O

1 OH OH

3a

OH OH

1

RuLn

O

H

4

H RuLn

1

1 RuLn

O

1 + 4 + 4

O O

2a

2a

O

O RuLn H O O

RuLn

1

2a

2a

2a RuLn

O

O O

PPh2

RuLn

3a

1

O O OH

HO

1

3b

2b

3.1 Cyclohexadiene Substrate. 3.1.1. Transformation from the Diol to the Ketol. The calculated free-energy profile for transformation of diol 1 to ketol 1′ is shown in Figure 1. The reaction starts 5



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with coordination of the hydroxyl group of 1 to the Ru center of the catalyst to form complex A-INa1, which is calculated to be exergonic by 5.8 kcal/mol. O–H bond cleavage then occurs via transition state A-TSa1 with an energy barrier of 21.0 kcal/mol to give Ru–alkoxide complex A-INa2. Subsequently, A-INa2 prepares for β-hydrogen elimination by dissociation of a CO ligand to give A-INa3. A-INa3 then undergoes β-hydrogen elimination by overcoming an energy barrier of 20.7 kcal/mol (A-TSa2) relative to A-INa2, generating Ru–dihydride complex A-INa4. The Ru–O bond is broken to generate ketol 1′ and ruthenium hydride complex H2RuLn′. Cyclohexadiene 2a further acts as a sacrificial hydrogen acceptor for reduction of H2RuLn′ to RuLn. Coordination of H2RuLn′ to 2a leads to formation of stable complex A-INa5. From A-INa5, hydrogen migration from Ru to the C atom through four-membered transition state A-TSa3 is relatively facile, with a calculated energy barrier of 5.5 kcal/mol. Hydrogen migration is calculated to be slightly endergonic with the resulting intermediate A-INa6 being 1.8 kcal/mol higher in energy than A-INa5. A-INa6 then isomerizes to the more stable η3-allyl intermediate A-INa7 by coordination of the double bond to the Ru center. The second hydrogen migration is accomplished via transition state A-TSa4 with an energy barrier of 13.2 kcal/mol. Finally, a ligand exchange process occurs to give cyclohexene 2a′ with regeneration of the RuLn catalyst.

6


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OH O

Relative Free Energies (kcal/mol)

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


H OH

RuLn

H O

15.2 A-TSa1

CO

OC

OH

0.0 RuLn

H

-5.8 A-INa1

RuLn

OH

RuLn

CO

O

H

H RuLn

6.6 H2RuLn 2a

OH

A-TSa3

1

-5.0 A-INa5 RuLn

A-INa2 OH

H O

H

1.3 A-TSa4

0.5

O

RuLn

RuLn

H

H

-9.0 H

Ru

H

H

OH O

3.3 A-INa4

H O

CO

1

H

6.5 A-INa3

Ru

PPh2

Ph2P

11.7 A-TSa2

PPh2

Ph2P

RuLn

H

H

RuLn

-3.2 A-INa6 RuLn H

RuLn

-6.5 A-INa8 CO

H

-11.9 A-INa7 RuLn

2a -16.6 RuLn

H

Figure 1. Calculated free-energy profile for transformation of diol 1 to ketol 1′ and regeneration of the catalyst. Free-energy values (kcal/mol) were computed with toluene as solvent. 3.1.2. Transformation of the Ketol to the Dione. The calculated free-energy profile for transformation of ketol 1′ to dione 1′′ is shown Figure S2. The reaction begins with coordination of 1′ to the Ru center of RuLn to form the A-INa9 intermediate, which is an exoergic process. Subsequent O–H deprotonation via three-centered transition-state A-TSa5 with an energy barrier of 21.3 kcal/mol relative to A-INa9 gives Ru–alkoxide intermediate A-INa10. A CO ligand then dissociates from 18e Ru(II) complex A-INa10 to give 16e Ru(II) complex A-INa11. From A-INa11, C–H deprotonation via transition state A-TSa6 gives Ru–dione intermediate A-INa12 with an energy barrier of 23.9 kcal/mol relative to A-INa10. The dione 1′′ dissociates and 2a then enters to form Ru–alkene complex A-INa13. Subsequently, two consecutive hydrogen migrations occur via transition states A-TSa7 and A-TSa8 with energy barriers of 5.5 and 13.2 kcal/mol, respectively. Regeneration of RuLn is realized by Ru–alkene dative bond cleavage followed by CO coordination. 7



Page 8 of 30

3.1.3. Dione–cyclohexadiene C–C Coupling. The calculated free-energy profile for dione–cyclohexadiene C–C coupling is shown in Figure 2. Figure 3 shows the optimized structures of the key stationary points labeled in Figure 2. Dione 1′′ initially coordinates to the ruthenium center of the active catalyst RuLn by two carbonyl groups to form intermediate A-INa17, which is exoergic by 6.8 kcal/mol. In A-INa17, the C1–O1, C2–O2, and C1–C2 distances are 1.356, 1.358, and 1.347 Å, respectively. Compared with isolated dione compound 1′′, the C1–O1 and C2–O2 distances are longer and the C1–C2 distance is shorter (the numbering of the atoms is given in Figure 2). This indicates that the Ru–O1 and Ru–O2 bonds are single covalent bonds. A CO ligand then dissociates from Ru(II) complex A-INa17 to give Ru(0) complex A-INa18. Compared with A-INa17, A-INa18 has shorter C1–O1 and C2–O2 distances (1.356 and 1.358 Å for A-INa17 vs 1.325 and 1.315 Å for A-INa18). These distance changes provide direct evidence for the Ru(0) center in A-INa18. In the following step, cyclohexadiene 2a attacks A-INa18 to complete the first C–C bond linkage via five-centered transition state A-TSa9 with an energy barrier of 12.2 kcal/mol. The second C–C bond is formed via five-centered transition state A-TSa10 by overcoming an energy barrier of 21.5 kcal/mol to give Ru(II) complex A-INa20. Because the second C–C bond linkage is less facile than the first C–C bond linkage, the first C–C bond linkage is fast and reversible. The relatively high stability of the oxaruthenacycle intermediate A-INa19 can be demonstrated by the experimental fact that a structurally similar oxaruthenacycle intermediate has been isolated.22 The higher energy barrier for the second C–C bond linkage is attributed to 8


Page 9 of 30

the coordination ability of the carbonyl group of A-TSa9 being stronger than that of the double bond of A-TSa10.


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


n RuL O1

1

2

RuLn O O

RuLn

12.2

O 2

A-TSb9

-2.3

O O

A-TSc9 2a RuLn

1

-23.4

-21.9

2a

O

n RuL

A-INc17

1

2a

-30.2

O

RuLn 1

O2 2

O O

O

A-INa17 1O

2 RuLn

-25.8

RuLn

A-TSa10

1

A-TSa9

O

-17.3

RuLn 1 2 O O

-34.1 CO

A-INa18 RuLn 1O 1

O2 2

RuLn

-34.4 A-INc18

-38.8 A-INa19

RuLn O O

O O 1 2

-33.2 A-INb19 -38.4 A-INa20

Figure 2. Calculated free-energy profile for dione–cyclohexadiene C–C coupling. Free-energy values (kcal/mol) were computed with toluene as solvent. As shown in Figure 2, A-INa18 determines formation of an exo or an endo product. In the straightforward pathway to the endo product (green line in Figure 2), there is a concerted process via transition state A-TSb9,23 in which two C–C bond linkages simultaneously occur, with an energy barrier of 46.3 kcal/mol. Because the endo-selective barrier (46.3 kcal/mol) is much higher than the exo-selective barrier (22.0 kcal/mol), the pathway to the resulting endo product is less kinetically favorable. The theoretical results for the exo-selectivity are consistent with experimental observations.11 The kinetic preference for formation of the exo product can be attributed to A-TSb9 being more rigid and forming in a much more concerted fashion than stepwise A-TSa9 and A-TSa10. As shown in the blue line in Figure 2, dione 1′′ can also coordinate to the ruthenium center of the active catalyst RuLn by one carbonyl group to form Ru(0) 9



Page 10 of 30

complex A-INc17, which is exoergic by 2.4 kcal/mol. Subsequently, A-INc17 is oxidized to Ru(II) complex A-INc18 through C–C bond linkage via five-centered transition state A-TSc9 with an energy barrier of 23.5 kcal/mol. The calculations show that transition state A-TSc9 is 19.6 kcal/mol higher in energy than the analogous transition state A-TSa9. The lower energy of A-TSa9 compared with A-TSc9 is because of coordination of two carbonyl groups to the Ru center. The shorter C1–C2 distance in A-TSa9 (1.408 Å) than in A-TSc9 (1.470 Å), as well as the longer C2–O2 distance in A-TSa9 (1.285 Å) than in A-TSc9 (1.231 Å), suggests that there is cooperation from the other carbonyl group in A-TSa9. The chirality of the C2 atom in the product is directly determined by the initial configurations of the A-INa19 and A-INc19 intermediates. In A-INa19, the carbonyl group is syn to the ether group, and the syn-product finally forms (black line in Figure 2). In A-INc19, the carbonyl group is anti to the ether group and the anti-product finally forms mediated by a second active catalyst RuLn molecule (Scheme 3). For the pathway of anti-product formation (Scheme 3), the transition state of the second C–C bond linkage A-TSc10 is much higher in free energy (5.2 kcal/mol). In view of A-TSc10 being 22.5 kcal/mol higher in energy than A-TSa10, the reaction prefers to occur by the path to give the syn product rather than that to give the anti product. This is because the A-TSc10 transition state along the anti-product formation pathway generates the very unstable diradical intermediate A-INc21 (−3.0 kcal/mol).

10


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Ru

Ru O1 C1-O1 = 1.356 C2-O2 = 1.358 C1-C2 = 1.347

O2 C1

C1-O1 = 1.325 C2-O2 = 1.315 C1-C2 = 1.364

C2

C1-C3 = 1.572 Ru-O1 = 2.130 Ru-C4 = 2.214 C1-C2 = 1.522 C2-O2 = 1.229

C2

C1

C4

O1

O2 C1 C2

O2

C1-C3 = 1.875 C2-C6 = 3.040 Ru-O1 = 2.130 Ru-O2 = 2.161

C3

A-TSa9

C2

C3 C2

Ru

Ru

Ru O1

C4 O2

C1

A-INa19

A-INa18

A-INa17

C1-C3 = 2.331 Ru-O1 = 2.155 Ru-C4 = 2.412 C1-C2 = 1.408 C2-O2 = 1.285

Ru O1

O2

O1

O1

C4

C1

C3

C1

O2 C2

C3 C6

A-TSb9

C1-C3 = 2.287 Ru-O1 = 2.122 Ru-C4 = 2.835 C1-C2 = 1.470 C2-O2 = 1.231

A-TSc9

Figure 3. Optimized structures of key species labeled in Figure 2. Key bond lengths are given in Å. Scheme 3. Pathway for Anti-Product Formationa RuLn O

O RuLn

RuLn

RuLn

O

O

A-INc19 -36.9 aFree-energy

CO

O

RuLn

RuLn

A-TSc10 5.2 O RuLn

A-INc20 -39.7

O

O RuLn

A-INc21 -3.0

values (kcal/mol) were computed with toluene as solvent.

3.1.4. Protonation leading to product 3a. Krische et al.11 found that the yield significantly increases when 3,5-Me2BzOH additive is introduced into the reaction system. In the literature,24 it is well-documented that the 1,2-diol substrate itself can act as a proton-transfer agent and facilitate protonation of A-INa20. In this stage, protonation of A-INa20 promoted by a 3,5-Me2BzOH (black line in Figure 4) and a 11



Page 12 of 30

1,2-diol (blue line in Figure 4) were both investigated. We first investigated hydrogen transfer between the 3,5-Me2BzOH and A-INa20. Binding of A-INa20 to 3,5-Me2BzOH 4 by a hydrogen bond affords intermediate A-INa21. The hydrogen bond weakens the carboxyl group O–H bond and consequently strengthens the O2–H interaction. As a consequence, the subsequent proton transfer promoted by the 3,5-Me2BzOH becomes facile. The calculated activation barrier for this elementary step via transition state A-TSa11 is −2.2 kcal/mol. Because there are several ligands surrounding the Ru center of the catalyst with strong trans influence, the O atom of the carboxyl group disfavors coordination to ruthenium in A-TSa11 and A-INa22. From A-INa22, the secondary 3,5-Me2BzOH approaches the O1 atom of the ether group and forms intermediate A-INa23 with a hydrogen bond. Hydrogen transfer then occurs via A-TSa12 to give A-INa24 with an energy barrier of −0.4 kcal/mol. In the final step, a ligand exchange process occurs to give the product 3a and the original catalyst RuLn is regenerated to start the next catalytic cycle. For the pathway assisted by 1,2-diol 1 (blue line in Figure 4), the calculated free energy of hydrogen-transfer transition state A-TSb11 is −22.1 kcal/mol, which is higher than that of A-TSa11. The hydride then transfers to the Ru center via A-TSb12 (ΔG‡ = 12.7 kcal/mol relative to A-INb22) to give hydride complex A-INb24 (−27.1 kcal/mol). Hydrogen migration from ruthenium to the O1 oxygen atom finally generates product 3a. The activation free energy barrier for the transition state of hydrogen transfer A-TSb13 is 28.2 kcal/mol. The A-TSa12 and A-TSb12 transition structures correspond to the highest energy points along the pathways mediated by the 12


Page 13 of 30

3,5-Me2BzOH and 1,2-diol, respectively (Figure 4). The lower basicity of the 1,2-diol substrate compared with the 3,5-Me2BzOH makes A-TSb12 higher in energy than A-TSa12, which is consistent with the experimental observation11 that a 3,5-Me2BzOH can increase the catalytic activity of the system. n

uL

R

n

OH O

R

uL

n

OH O

R

H

H


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


1O O2

OH

uL

O

uL

R

H

O O

n

HO

O

O HO

O O

n uL H O O HO

HO

n

uL

R

R

n uL R H 1 O HO 2 1

n

H

O HO

uL

R

H

O HO

1

2

2

A-INb21

A-TSb11

A-INb23

A-INb22

A-INb25

A-INb24

A-TSb12

A-TSb13

-10.0

-11.1

A-TSb12 -22.1

1

-20.5

-22.7 A-INb22

A-TSb11

A-INb23

3a -27.1

-29.9

1

A-INb24

A-INb21 -38.4 -38.5

A-INa20 O

OH

A-TSb13

-40.7 A-TSa11

A-INa21

-38.9 A-INa22

CO -28.1 RuLn

4 -39.8

-40.2

A-INa23

A-TSa12

-39.7 A-INa24

-39.3

CO

A-INb25

1 + 4 + 4

-47.5 3a

4

H

RuLn

1 O O2 1

O

RuLn H O O

2

A-INa21

A-TSa11

O

O

O

O O

O

RuLn H 1O O 2 1 2

A-INa22

H

H RuLn 1O O2 1 2

A-INa23

O

O

O

O O

A-INa25

O

O O

H

H RuLn O O

A-TSa12

1

O O

O

H

H RuLn

RuLn O

O

O

O

O O

A-INa24

A-INa25

Figure 4. Calculated free-energy profiles for the protonation process leading to product 3a assisted by 1,2-diol 1 (blue) and 3,5-Me2BzOH 4 (black). Free-energy values (kcal/mol) were computed with toluene as solvent. 3.1.5. Competing aromatization mechanism. As mentioned in Section 1, aromatization to benzene competes with cycloaddition to the bridged bicycle for cyclohexadiene. We calculated the aromatization mechanism and compared it with the cycloaddition mechanism. The calculated free-energy profile for the competing aromatization mechanism is shown in Figure 5. The pathway starts with coordination of substrate 2a to the Ru center to give A-INd17, which is calculated to be endergonic by 3.2 kcal/mol. From A-INd17, hydride is transferred to the Ru center via A-TSd9 13



to give ruthenium hydride complex A-INd18. We also considered that the hydride transfer begins with the Ru–alkene complex A-INe18. The calculations show that the free energy of the transition state A-TSe9 for the hydride transfer started from the Ru–alkene complex A-INe18 is 1.0 kcal/mol higher than that of the transition state A-TSd9. A CO ligand then dissociates from A-INd18 to give less stable complex A-INd19. Upon formation of intermediate A-INd19, a second hydride migrates to the Ru atom through transition state A-TSd10 with an activation barrier of 13.8 kcal/mol relative to A-INd18 to give stable dihydride species A-INd20, in which the benzene ring coordinates to Ru by the C=C double bond in a η2 fashion with Ru–C distances of 3.219 and 3.271 Å. The highest energy point leading to benzene is A-TSd9, which is energetically less favorable by 10.0 kcal/mol compared with that of A-TSa9 leading to bridged bicycle 3a. Therefore, from a kinetic point of view, we can understand that no aromatization of cyclohexadiene was observed by Krische and co-workers11. The preference for A-TSa9 over A-TSd9 can be attributed to the distortion energy of the three-membered ring of A-TSd9 being larger than that of the five-membered ring of A-TSa9. Relative Free Energies (kcal/mol)

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

Page 14 of 30

H

RuLn

RuLn

-11.9 A-TSd9

H

H

-10.9 A-TSe9

H RuLn

RuLn

2a

RuLn

-20.2

H

A-INd17

-23.4 RuLn

H

H RuLn H

-18.2

-18.8

A-INd19

A-TSd10

H

-23.9

RuLn

A-INe19

2a RuLn

RuLn

-39.9

A-INd18

H

CO

-32.6 H RuLn

A-INe17 CO

-43.8 A-INe18

-30.4 A-INd20

benzene -33.2 H2RuLn

Figure 5. Calculated free-energy profile for the competing aromatization mechanism. 14


Page 15 of 30 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


Free-energy values (kcal/mol) were computed with toluene as solvent. 3.2 Norbornadiene Substrate The calculated free-energy profile for dione–norbornadiene C–C coupling is shown in Figure 6. Figure 7 shows the optimized structures of the key stationary points labeled in Figure 6. The cycle starts with substrate 1′′ coordinating to the Ru center to give B-INa1, which is calculated to be exoergic by 7.3 kcal/mol. Subsequently, the binding of ruthenium to the two carbonyl groups switches from the η1 mode to the η2 mode with dissociation of a CO ligand. From B-INa2, C–C bond coupling can occur via transition state B-TSa1 to give oxaruthenacycle B-INa3. The calculated energy barrier for this step is 13.4 kcal/mol relative to B-INa2. For B-TSa1, the coupling C1–C3 bond distance is 2.679 Å, while the Ru–C5 bond shortens to 2.546 Å. B-INa3 is 12.8 kcal/mol more stable than B-INa2 owing to formation of the five-membered ruthenium heterocycle. The transition state B-TSa2 for the second C–C bond coupling has an activation barrier of 26.3 kcal/mol. From the structure of B-TSa2, the C2–C4 and C5–C6 distances are 1.832 and 2.177 Å, indicating formation of a three-membered ring with the second coupling between norbornadiene and the 1,2-diol.

15



RuLn RuLn


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

Page 16 of 30

O O

O O 3

4 6

1

2

B-TSb1

2 5

RuLn O O

2.6

1

B-TSa1

2b

4

1

23.3

3

0.00

6

15.4 B-TSb2

5

RuLn

2.7

6

3 2

5

O O

B-TSa2

4

5 6

3

1 4

2

RuLn 2b RuLn

O

-7.3 B-INa1

O

-10.8 B-INa2

RuLn

1

O

O

RuLn

O O

CO

O O

RuLn O

O

RuLn O O

-23.6

RuLn

B-INa3

-30.0

O O

-31.9

B-INb4 -33.2

B-INb3

B-INa4

Figure 6. Calculated free-energy profile for dione–norbornadiene C–C coupling. Free-energy values (kcal/mol) were computed with toluene as solvent.

Ru

Ru O1 C1-C3 = 2.679 Ru-O1 = 2.138 Ru-C5 = 2.546

Ru C5

O2 C3

C1 C2

C4

B-TSa1

C6

Ru-O2 = 2.147 C2-C4 = 1.832 C5-C6 = 2.177

O2

C1

C3 C2

B-TSa2

C4

C6

C4

O1

C5

O1

C1-C3 = 2.781 Ru-O1 = 2.189 Ru-C4 = 2.147 C5-C6 = 2.177

O2

C1 C2

O1

C6

C3 C5

Ru-O2 = 2.087 C2-C4 = 2.297 Ru-C4 = 2.682

O2

Ru C1 C3 C4

C2 C5

B-TSb1

C6

B-TSb2

Figure 7. Optimized structures of key species labeled in Figure 6. Key bond lengths are given in Å. To investigate the origin of the exo-selectivity for norbornadiene 2b, we also investigated the pathway for formation of the endo product. For the green line in Figure 6, the first carbon–carbon bond coupling between norbornadiene and the 1,2-diol concurrently occurs with C5–C6 arene bond linkage. The free energy of the transition state for the first carbon–carbon bond coupling (B-TSb1) is 23.3 kcal/mol. The second carbon–carbon bond coupling between norbornadiene and the 1,2-diol then proceeds via transition state B-TSb2 to give the B-INb4 intermediate (−30.0 kcal/mol). The activation barrier of transition state B-TSb2 is 47.3 kcal/mol. The 16


Page 17 of 30 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


highest energy point leading to the endo product is B-TSb1, which is 20.6 kcal/mol energetically less favorable than B-TSa2 leading to the exo product. Therefore, there is strong exo-selectivity, which is consistent with the experimental observation11 that only the exo product 3b forms. To understand the origin of this exo-selectivity, distortion/interaction analysis25,26 was performed for the competing transition states (B-TSa1 and B-TSb1). The results are shown in Scheme 4. Each transition state structure was separated into two fragments (the distorted catalyst and substrate), and single point energy calculations were performed for each of the distorted fragments. According to the interaction energies of the two fragments (ΔEint), B-TSb1 is 26.9 kcal/mol less energetically favorable than B-TSa1 (−9.9 vs −36.8 kcal/mol). However, the distortion energy of B-TSa1 (ΔEdist) is 50.6 kcal/mol smaller than that of B-TSb1 (19.3 vs 69.9 kcal/mol). Comparing the two C–C bond linkage transition states (B-TSa1 and B-TSb1), the substrate distortion is the major factor controlling the exo-selectivity. Scheme 4. Distortion/Interaction Analysis of the Competing Transition States B-TSa1 and B-TSb1.

Ru Ru O1

C5

O2 C3

C1 C2

C6

C1-C3 = 2.679 Ru-O1 = 2.138 Ru-C5 = 2.546

C4

C4

O1

O2

C1 C2

C6

C3

C1-C3 = 2.781 Ru-O1 = 2.189 Ru-C4 = 2.147 C5-C6 = 2.177

C5

B-TSa1

B-TSb1

17



The steps following formation of the B-INa4 intermediate are associated with generation of the product 3b. The calculated free-energy profile of the protonation process leading to 3b is shown in Figure 8. Binding of B-INa4 with 1 by a hydrogen bond gives intermediate B-INa5. Subsequently, 1,2-diol 1 undergoes a proton-transfer step to the ether group to give B-INa6. The predicted energy barrier (B-TSa3) for this proton transfer step is 5.9 kcal/mol relative to B-INa5 and 9.4 kcal/mol relative to B-INa4. Conformational change (B-INa6 → B-INa7) through facile dissociation of the hydroxyl group from the Ru center makes the ether carbon atom proximal to Ru, favoring subsequent hydrogen migration. The hydrogen is then transferred to the Ru atom via transition state B-TSa4, giving the intermediate B-INa8 and 1′. The calculated energy barrier for this step is 8.9 kcal/mol relative to B-INa7 (i.e., 11.3 kcal/mol relative to B-INa6). After transformation of B-INa8 to B-INa9 with Ru–CO coordination, ether H migration to the Ru-attached O atom via B-TSa5 gives the final product 3b with release of the RuLn catalyst. The energy demand for the H-migration step is 26.7 kcal/mol relative to B-INa9. 

Ln Ru H

HO

Ln H

Ru

O O HO


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

Page 18 of 30

Ln

Ru

O HO

OH



O H

-13.1

O O

-14.0

B-TSa4

B-TSa5

O OH

-22.0 -23.8 B-TSa3

OH

-33.2 B-INa4

Ru

-29.7

 Ln O Ru H O O

OH

 Ln

O H

B-INa5 OH



B-INa6

OH

1

B-INa7

-24.4

O O

Ln Ru O

HO

O HO

3b

-29.9

-30.9 B-INa8 n

L Ru

RuLn CO

Ln H

Ru

H

O HO

OH

HO

1

-40.7

O HO

B-INa9

Figure 8. Calculated free-energy profile for the protonation process leading to 18


Page 19 of 30 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


product 3b. Free-energy values (kcal/mol) were computed with toluene as solvent. 3.3 1,4-Cyclohexadiene Substrate Krische et al.11 found that non-conjugated dienes also participate in [4+2] cycloaddition to form a bridged bicycle with high yield. Because non-conjugated dienes can transform to conjugated dienes through olefin isomerization, we first investigated the olefin-isomerization pathway promoted by Ru(II) hydride intermediate H2RuLn′.27 The calculated free-energy profile for transformation of non-conjugated diene 2c to conjugated diene 2a is shown in Figure S3. Isomerization begins with coordination of the C–C double bond of 2c to the Ru center of H2RuLn′ to form π complex C-INa1, which is exoergic by 9.5 kcal/mol. Insertion of the double bond into the Ru–H bond occurs through transition state C-TSa1 to give Ru(II)–alkyl intermediate C-INa2. Subsequently, C-INa2 prepares for β-hydride elimination by isomerizing to C-INa3. From C-INa3, β-hydride elimination via transition state C-TSa2 gives the C-INa4 intermediate, from which a ligand dissociation step produces the conjugated diene 2a and H2RuLn′. The results show that the energy barrier for transformation from non-conjugated diene 2c to conjugated diene 2a is low (8.3 kcal/mol with respect to C-INa1), and it is thus kinetically accessible. Therefore, the calculations indicate that the non-conjugated diene first isomerizes to the conjugated diene before C–C bond coupling. 4. CONCLUSIONS The mechanisms and origin of the exo- and diastereoselectivity of ruthenium(0)-catalyzed transfer hydrogenative cycloaddition of 1,2-diols with 19



Page 20 of 30

cyclohexadiene and norbornadiene have been investigated in detail by the DFT method. The coupling reaction between the dione and cyclohexadiene consists of four major steps: transformation from the diol to the ketol, transformation of the ketol to the dione, dione–cyclohexadiene C–C coupling, and final protonation leading to the product. The DFT results indicate that the exo-selective pathway proceeds by novel two-step successive C–C coupling, while the endo-selective pathway proceeds by the C–C coupling reaction in a conventionally concerted manner. The exo-selectivity for the cyclohexadiene substrate can be attributed to the flexible two-step successive pathways and the exo-selectivity for the norbornadiene substrate can be explained by the distortion energy. The preference for dione–cyclohexadiene C–C coupling over aromatization to benzene can be attributed to the distortion energy of the three-membered ring in the transition state of hydrogen migration being larger than that of the five-membered ring in the transition state of C–C coupling. We found that the second C–C bond linkage is diastereoselectivity determining, which agrees well the experimentally observed selectivity. Calculations of the pathways with and without a carboxylic acid additive show that the carboxylic acid affects the protonation step after C–C bond coupling between the dione and cyclohexadiene. We expect that the mechanistic insight revealed by the calculations in this study will guide the development of synthesis of bridged carbocycles. Supporting Information Additional

computational

results,

calculated

imaginary

frequencies

of

all 20


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transition-state species, xyz coordinate file, and energies. ACKNOWLEDGEMNTS This work was supported by the National Natural Science Foundation of China (Grant No. 21573095), the Science and Technology Program of Guangzhou (Grant No. 201707010269), and the high-performance computing platform of Jinan University. REFERENCES (1) For selected reviews, see: (a) Filippini, M.-H.; Rodriguez, J. Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry. Chem. Rev. 1999, 99, 27−76. (b) Zhao, W. Novel Syntheses of Bridge-Containing Organic Compounds. Chem. Rev. 2010, 110, 1706−1745. (c) Pressset, M.; Coquerel, Y.; Rodriguez, J. Syntheses and Applications of Functionalized Bicyclo[3.2.1]octanes: Thirteen Years of Progress. Chem. Rev. 2013, 113, 525−595. (d) Stockdale, T. P.; Williams, C. M. Pharmaceuticals that Contain Polycyclic Hydrocarbon Scaffolds. Chem. Soc. Rev. 2015, 44, 7737−7763. (e) Le Bideau, F.; Kousara, M.; Chen, L.; Wei, L.; Dumas, F. Tricyclic Sesquiterpenes from Marine Origin. Chem. Rev. 2017, 117, 6110−6159. (f) Thombare, V. J.; Hutton, C. A. Bridged Bicyclic Peptides: Structure and Function. Peptide Science 2018, 110, e24057. (2) For selected reviews, see: (a) Roche, S. P.; Porco, J. A., Jr. Dearomatization Strategies in the Synthesis of Complex Natural Products. Angew. Chem., Int. Ed., 2011, 50, 4068−4093. (b) Richard, J.-A.; Pouwer, R. H.; Chen, D. Y.-K.; The Chemistry of the Polycyclic Polyprenylated Acylphloroglucinols. Angew. Chem., Int. Ed., 2012, 51, 4536−4561. (c) Parvatkar, P. T.; Kadam, H. K.; Tilve, S. G. Intramolecular Diels-Alder Reaction as A Key Step in Tandem or Sequential Processes: A Versatile Tool for the Synthesis of Fused and Bridged Bicyclic or 21



Page 22 of 30

Polycyclic Compounds. Tetrahedron 2014, 70, 2857−2888. (d) Xu, J.; Lacoske, M. H.; Theodorakis, E. A. Neurotrophic Natural Products: Chemistry and Biology. Angew. Chem., Int. Ed. 2014, 53, 956−987. (e) Büschleb, M.; Dorich, S.; Hanessian, S.; Tao, D.; Schenthal, K. B.; Overman, L. E. Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms. Angew. Chem., Int. Ed. 2016, 55, 4156−4186. (3) Ciamician, G.; Silber, P. Chemische Lichtwirkungen. Chem. Ber. 1908, 41, 1928−1935. (4) Diels, O.; Alder, K. Synthesen in der hydroaromatischen Reihe. Justus Liebigs Ann. Chem. 1928, 460, 98−122. (5) For selected reviews on transition-metal-catalyzed cycloadditions, see: (a) Lautens, M.; Klute, W.; Tam, W. Transition Metal-Mediated Cycloaddition Reactions. Chem. Rev. 1996, 96, 49−92. (b) Gulías, M.; López, F.; Mascareñas, J. L. Development of Transition-metal-catalyzed Cycloaddition Reactions Leading to Polycarbocyclic Systems. Pure Appl. Chem. 2011, 83, 495−506. (c) Johansson, J. R.; Beke-Somfai, T.; Said Stålsmeded, A.; Kann, N. Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications. Chem. Rev. 2016, 116, 14726−14768. (d) Cheng, Q.-Q.; Deng, Y.; Lankelma, M.; Doyle, M. P. Cycloaddition Reactions of Enoldiazo Compounds. Chem. Soc. Rev. 2017, 46, 5425−5443. (6) (a) Ketcham, J. M.; Shin, I.; Montgomery, T. P.; Krische, M. J. Catalytic Enantioselective C−H Functionalization of Alcohols by Redox-Triggered Carbonyl Addition: Borrowing Hydrogen, Returning Carbon. Angew. Chem., Int. Ed. 2014, 53, 9142−9150. (b) Dechert Schmitt, A.-M. R.; Schmitt, D. C.; Gao, X.; Itoh, T.; Krische, M. J. Polyketide Construction via Hydrohydroxyalkylation and Related Alcohol C−H Functionalizations: Reinventing the Chemistry of Carbonyl Addition. Nat. Prod. Rep. 22


Page 23 of 30 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


2014, 31, 504−513. (c) Perez, F.; Oda, S.; Geary, L. M.; Krische, M. J. Ruthenium-Catalyzed

Transfer

Hydrogenation

for

C−C

Bond

Formation:

Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs. Top. Curr. Chem. 2016, 374, 365−387. (d) Nguyen, K. D.; Park, B. Y.; Luong, T.; Sato, H.; Garza, V. J.; Krische, M. J. Metal-Catalyzed Reductive Coupling of Olefin-Derived Nucleophiles: Reinventing Carbonyl Addition. Science 2016, 354, 300 (aah5133−1-5). (e) Feng, J.; Kasun, Z. A.; Krische, M. J. Enantioselective Alcohol C−H Functionalization for Polyketide Construction: Unlocking Redox-Economy and Site-Selectivity for Ideal Chemical Synthesis. J. Am. Chem. Soc. 2016, 138, 5467 –5478. (f) Kim, S. W.; Zhang, W.; Krische, M. J. Catalytic Enantioselective Carbonyl Allylation and Propargylation via Alcohol-Mediated Hydrogen Transfer: Merging the Chemistry of Grignard and Sabatier. Acc. Chem. Res. 2017, 50, 2371–2380. (7) For selected reviews, see: (a) Gallezot, P. Conversion of Biomass to Selected Chemical Products. Chem. Soc. Rev. 2012, 41, 1538−1558. (b) Dapsens, P. Y.; Mondelli, C.; Pérez-Ramírez, J. Biobased Chemicals from Conception toward Industrial Reality: Lessons Learned and To Be Learned. ACS Catal. 2012, 2, 1487−1499. (c) Zheng, M.; Pang, J.; Sun, R.; Wang, A.; Zhang, T. Selectivity Control for Cellulose to Diols: Dancing on Eggs. ACS Catal. 2017, 7, 1939−1954. (8) For selected reviews, see: (a) Nicholas, K. M. Selective Catalysis for Renewable Feedstocks and Chemicals. Top. Curr. Chem. 2014, 353, 163−184. (b) Raju, S.; Moret, M.-E;

Klein

Gebbink,

R.

J.

M.

Rhenium-Catalyzed

Dehydration

and

Deoxydehydration of Alcohols and Polyols: Opportunities for the Formation of Olefins from Biomass. ACS Catal. 2015, 5, 281−300. (c) Dethlefsen, J. R.; Fristrup, P. Rhenium-Catalyzed Deoxydehydration of Diols and Polyols. ChemSusChem 2015, 8, 767−775. (d) Petersen, A. R.; Fristrup, P. New Motifs in Deoxydehydration: Beyond 23



Page 24 of 30

the Realms of Rhenium. Chem. Eur. J. 2017, 23, 10235−10243. (9) Selected examples, see: (a) Saxena, A.; Perez, F.; Krische, M. J. Ruthenium(0) Catalyzed Endiyne−α-Ketol [4 + 2] Cycloaddition: Convergent Assembly of Type II Polyketide Substructures via C−C Bond Forming Transfer Hydrogenation. J. Am. Chem. Soc. 2015, 137, 5883−5886. (b) Sato, H.; Bender, M.; Chen, W.; Krische, M. J. Diols, α-Ketols, and Diones as 22π Components in [2+2+2] Cycloadditions of 1,6-Diynes via Ruthenium(0)-Catalyzed Transfer Hydrogenation. J. Am. Chem. Soc. 2016, 138, 16244−16247. (c) Bender, M.; Turnbull, B. W. H.; Ambler, B. R.; Krische, M. J. Ruthenium-catalyzed Insertion of Adjacent Diol Carbon Atoms into C−C bonds: Entry to Type II polyketides. Science 2017, 357, 779−781. (10) (a) Geary, L. M.; Glasspoole, B. W.; Kim, M. M.; Krische, M. J. Successive C−C Coupling of Dienes to Vicinally Dioxygenated Hydrocarbons: Ruthenium Catalyzed [4 + 2] Cycloaddition across the Diol, Hydroxycarbonyl, or Dione Oxidation Levels. J. Am. Chem. Soc. 2013, 135, 3796−3799. (b) Geary, L. M.; Chen, T.-Y.; Montgomery, T. P.; Krische, M. J. Benzannulation via Ruthenium-Catalyzed Diol−Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes. J. Am. Chem. Soc. 2014, 136, 5920−5922. (c) Kasun, Z. A.; Geary, L. M.; Krische, M. J. Ring Expansion of Cyclic 1,2-diols to Form Medium Sized Rings via Ruthenium Catalyzed Transfer Hydrogenative [4+2] Cycloaddition. Chem. Comm. 2014, 50, 7545−7547. (d) Chen, T.-Y.; Krische, M. J. Regioselective Ruthenium Catalyzed Hydrohydroxyalkylation of Dienes with 3-Hydroxy-2-oxindoles: Prenylation, Geranylation, and Beyond. Org. Lett. 2013, 15, 2994−2997. (11) Sato, H.; Fukaya, K.; Poudel, B. S.; Krische, M. J. Diols as Dienophiles: Bridged Carbocycles via Ruthenium(0)-Catalyzed Transfer Hydrogenative Cycloadditions of Cyclohexadiene or Norbornadiene. Angew. Chem., Int. Ed. 2017, 56, 14667−14671. 24


Page 25 of 30 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


(12) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; 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.; Keith, T; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; 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, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision D.01; Gaussian, Inc.: Wallingford CT, 2013. (13) (a) Lee, C.; Yang, W.; Parr, R. G. Development of the Colic-Salvetti Correlation-Energy Formula into a Functional of the Electron Density. Phys. Rev. B, 1988, 37, 785−789. (b) Becke, A. D. Density-Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648−5652. (c) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields. J. Phys. Chem. 1994, 98, 11623−11627. (14) (a) Hay, P. J.; Wadt, W. R. Ab Initio Effective Core Potentials for Molecular Calculations. Potentials for K to Au Including the Outermost Core Orbitals. J. Chem. Phys. 1985, 82, 299−310. (b) Wadt, W. R.; Hay, P. J. Ab Initio Effective Core Potentials for Molecular Calculations. Potentials for Main Group Elements Na to Bi. J. 25



Page 26 of 30

Chem. Phys. 1985, 82, 284−298. (15) Ehlers, A. W.; Böhme, M.; Dapprich, S.; Gobbi, A.; Höllwarth, A.; Jonas, V.; Köhler, K. F.; Stegmann, R.; Veldkamp A.; Frenking, G. A set of f-polarization Functions for Pseudo-Potential Basis sets of the Transition Metals SC-Cu, Y-Ag and La-Au. Chem. Phys. Lett. 1993, 208, 111−114. (16) (a) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. Self-Consistent Molecular Orbital Methods. XX. A Basis set for Correlated Wave Functions. J. Chem. Phys. 1980, 72, 650−654. (b) McLean, A. D.; Chandler, G. S. Contracted Gaussian Basis Sets for Molecular Calculations. I. Second Row Atoms, Z=11-18. J. Chem. Phys. 1980, 72, 5639−5648. (17) (a) Fukui, K. Formulation of the Reaction Coordinate. J. Phys. Chem. 1970, 74, 4161−4163. (b) Fukui, K. The Path of Chemical Reactions-the IRC Approach. Acc. Chem. Res. 1981, 14, 363−368. (18) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Performance of SM6, SM8, and SMD on the SAMPL1 Test Set for the Prediction of Small-Molecule Solvation Free Energies. J. Phys. Chem. B 2009, 113, 4538−4543. (19) (a) Zhao, Y.; Schultz, N. E. Truhlar, D. G. Exchange-Correlation Functional with Broad Accuracy for Metallic and Nonmetallic Compounds, Kinetics, and Noncovalent Interactions. J. Chem. Phys. 2005, 123, 161103/1−161103/4. (b) Zhao, Y.; Truhlar, D. G. Density Functionals with Broad Applicability in Chemistry. Acc. Chem. Res. 2008, 41, 157−167. (c) Zhao, Y.; Truhlar, D. G. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 other Functionals. Theor. Chem. Acc. 2008, 120, 215−241. (d) Zhao, Y.; Truhlar, D. G. 26


Page 27 of 30 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


Benchmark Energetic Data in a Model System for Grubbs II Metathesis Catalysis and Their Use for the Development, Assessment, and Validation of Electronic Structure Methods. J. Chem. Theory Comput. 2009, 5, 324−333. (20) Weigend, F.; Ahlrichs, R. Balanced Basis Sets of Split Valence, Triple Zeta Valence and Quadruple Zeta Valence Quality for H to Rn: Design and Assessment of Accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297−3305. (21) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A Consistent and Accurate ab Initio Parametrization of Density Functional Dispersion Correction (DFT-D) for the 94 Elements H-Pu. J. Chem. Phys. 2010, 132, 154104−154119. (22) Park, B. Y.; Montgomery, T. P.; Garza, V. J.; Krische, M. J. Ruthenium Catalyzed Hydrohydroxyalkylation of Isoprene Employing Heteroaromatic Secondary Alcohols: Isolation and Reversible Formation of the Putative Metallacycle Intermediate. J. Am. Chem. Soc. 2013, 135, 16320−16323. (23) For some theoretical calculations on the endo:exo selectivity, see: (a) Norrby, P.-O.; Mader, M. M.; Vitale, M.; Prestat, G.; Poli, G. Rationalizing Ring-Size Selectivity in Intramolecular Pd-Catalyzed Allylations of Resonance-Stabilized Carbanions. Organometallics 2003, 22, 1849−1855. (b) Fosu, E.; Tia, R.; Adei, E. Mechanistic Studies on Diels-Alder [4+2] Cycloaddition Reactions of α,β-Substituted Cyclobutenones: Role of Substituents in Regio- and Stereoselectivity. Tetrahedron 2016, 72, 8261−8273. (c) Levandowski, B. J.; Hamlin, T. A.; Helgeson, R. C.; Bickelhaupt, F. M.; Houk, K. N. Origins of the Endo and Exo Selectivities in Cyclopropenone, Iminocyclopropene, and Triafulvene Diels-Alder Cycloadditions. J. Org. Chem. 2018, 83, 3164−3170. (d) Maiga-Wandiam, B.; Corbu, A.; Massiot, G.; Sautel, F.; Yu, P.; Lin, B. W. Y.; Houk, K. N.; Cossy, J. Intramolecular Diels-Alder Approaches to the Decalin Core of Verongidolide: The Origin of the exo-Selectivity, 27



Page 28 of 30

a DFT Analysis. J. Org. Chem. 2018, 83, 5975−5985. (e) Leal, R. C.; Pereira, D. H.; Custodio, R. An Energetic Analysis of the Diels-Alder endo:exo Selectivity Reaction by Using Composite Methods. Computational and Theoretical Chemistry 2018, 1123, 161−168. (f) Merzoud, L.; Saal, A.; Moussaoui, R.; Ouamerali, O.; Morell, C.; Chermette, H. Fluorine Substituent Effect on the Stereochemistry of Catalyzed and Non-Catalyzed Diels-Alder Reactions. The Case of R-butenone with Cyclopentadiene: a Computational Assessment of the Mechanism. Phys. Chem. Chem. Phys. 2018, 20, 16102−16116. (24) The 1,2-diol substrate itself can act as a proton transferring agent, see: (a) Blum, Y.; Shvo, Y. Catalytic Oxidation of Alcohols to Esters with Ru

3

(CO)

12.

J. Org.

Chem. 1984, 263, 93−107. (b) Meijer, R. H.; Ligthart, G. B. W. L.; Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof, L. A. RuCl2[S-BINAP]-Catalyzed Synthesis of Aldehydes and Ketones by Dehydrogenation of Alcohols. J. Mol. Catal. A: Chem. 2004, 218, 29−40. (c) Meijer, R. H.; Ligthart, G. B. W. L.; Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof, L. A.; Mills, A. M.; Kooijman, H.; Spek, A. L. Triruthenium Dodecacarbonyl/Triphenylphosphine Catalyzed Dehydrogenation of Primary and Secondary Alcohols. Tetrahedron 2004, 60, 1065−1072. (d) Bähn, S.; Tillack, A .; Imm, S.; Mevius, K.; Michalik, D.; Hollmann, D.; Neubert, L.; Beller, M. Ruthenium-Catalyzed Selective Monoamination of Vicinal Diols. ChemSusChem 2009, 2, 551−557. (e) Pingen, D.; Müller, C.; Vogt, D. Direct Amination of Secondary Alcohols Using Ammonia. Angew. Chem., Int. Ed. 2010, 49, 8130−8133. (f) Alsabeh, P.G.; Mellmann, D.; Junge, H.; Beller, M. Ruthenium-Catalyzed Hydrogen Generation from Alcohols and Formic Acid, Including Ru-Pincer-Type Complexes. Top. Organomet. Chem. 2014, 48, 45−79. (g) Pingen, D.; Lutz, M.; Vogt, D. Mechanistic Study on the Ruthenium-Catalyzed Direct Amination of Alcohols. 28


Page 29 of 30 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


Organometallics 2014, 33, 1623−1629. (25) (a) Ess, D. H.; Houk, K. N. Distortion/Interaction Energy Control of 1,3-Dipolar Cycloaddition Reactivity. J. Am. Chem. Soc. 2007, 129, 10646−10647. (b) Legault, C. Y.; Garcia, Y.; Merlic, C. A.; Houk, K. N. Origin of Regioselectivity in Palladium-Catalyzed Cross Coupling Reactions of Polyhalogenated Heterocycles. J. Am. Chem. Soc. 2007, 129, 12664−12665. (c) Ess, D. H.; Houk, K. N. Theory of 1,3-Dipolar Cycloadditions: Distortion/Interaction and Frontier Molecular Orbital Models. J. Am. Chem. Soc. 2008, 130, 10187−10198. (d) Hong, X.; Liang, Y.; Houk, K. N. Mechanisms and Origins of Switchable Chemoselectivity of Ni-Catalyzed C(aryl)−O and C(acyl)−O Activation of Aryl Esters with Phosphine Ligands. J. Am. Chem. Soc. 2014, 136, 2017−2025. (e) Green, A. G.; Liu, P.; Merlic, C. A.; Houk, K. N. Distortion/Interaction Analysis Reveals the Origins of Selectivities in Iridium-Catalyzed C−H Borylation of Substituted Arenes and 5-Membered Heterocycles. J. Am. Chem. Soc. 2014, 136, 4575−4583. (f) Liu, F.; Liang, Y.; Houk, K. N. Theoretical Elucidation of the Origins of Substituent and Strain Effects on the Rates of Diels-Alder Reactions of 1,2,4,5 Tetrazines. J. Am. Chem. Soc. 2014, 136, 11483−11493. (26) The distortion/interaction model is also called the activation-strain model: (a) Zeist, W-J. V.; Bickelhaupt, F. M. The Activation Strain Model of Chemical Reactivity. Org. Biomol. Chem. 2010, 8, 3118−3127. (b) Fernández, I.; Cossío, F. P.; Bickelhaupt, F. M. Aromaticity and Activation Strain Analysis of [3+2] Cycloaddition Reactions between Group 14 Heteroallenes and Triple Bonds. J. Org. Chem. 2011, 76, 2310−2314. (c) Fernández, I.; Bickelhaupt, F. M.; Alder-Ene Reaction: Aromaticity and Activation-Strain Analysis. J. Comput. Chem. 2012, 33, 509−516. (d) Fernández, I.; Wolters, L. P.; Bickelhaupt, F. M.; Controlling the 29



Page 30 of 30

Oxidative Addition of Aryl Halides to Au(I). J. Comput. Chem. 2014, 35, 2140−2145. (27) Transition-metal-catalyzed olefin isomerization has been widely proposed that with the aid of the M−H species, see: (a) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 5th ed.; Wiley: Hoboken, NJ, 2009; pp 229−231. (b) Werner, E. W.; Mei, T.-S.; Burckle, A. J.; Sigman, M. S. Enantioselective Heck Arylations of Acyclic Alkenyl Alcohols Using a Redox-Relay Strategy. Science 2012, 338, 1455−1458. (c) Henriksen, S. T.; Tanner, D.; Cacchi, S.; Norrby, P.-O. DFT-Based Explanation of the Effect of Simple Anionic Ligands on the Regioselectivity of the Heck Arylation of Acrolein Acetals. Organometallics 2009, 28, 6201−6205. (d) Hamasaki, T.; Aoyama, Y.; Kawasaki, J.; Kakiuchi, F.; Kochi, T. Chain Walking as a Strategy for Carbon-Carbon Bond Formation at Unreactive Sites in Organic Synthesis: Catalytic Cycloisomerization of Various 1,n-Dienes. J. Am. Chem. Soc. 2015, 137, 16163−16171. (e) Dang, Y.; Qu, S.; Wang, Z.-X.; Wang, X. A Computational Mechanistic Study of an Unprecedented Heck-Type Relay Reaction: Insight into the Origins of Regio- and Enantioselectivities. J. Am. Chem. Soc. 2014, 136, 986−998. (f) Zhang, M.; Hu, L.; Lang, Y.; Cao, Y.; Huang, G. Mechanism and Origins of Regio- and Enantioselectivities of Iridium-Catalyzed Hydroarylation of Alkenyl Ethers. J. Org. Chem. 2018, 83, 2937−2947.

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Theoretical Study of Ruthenium(0)-Catalyzed Transfer Hydrogenative

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