Methanol-Assisted Phthalimide Ring Opening ... - ACS Publications

Subscriber access provided by UNIV OF NEW ENGLAND ARMIDALE

A: Kinetics and Dynamics

Methanol-Assisted Phthalimide Ring Opening: Concerted or Stepwise Mechanism? Weihao Chen, Xuejiao J. Gao, and Xingfa Gao J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b11347 • Publication Date (Web): 07 Mar 2018 Downloaded from http://pubs.acs.org on March 8, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 16 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

The Journal of Physical Chemistry

Methanol-Assisted Phthalimide Ring Opening: Concerted or Stepwise Mechanism? WeiHao Chen, Xuejiao J. Gao,* and Xingfa Gao*

Key Laboratory of Functional Small Organic Molecule, Ministry of Education, and Jiangxi’s Key Laboratory of Green Chemistry, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China

ABSTRACT: The opening of the five-membered ring is the essential step for phthalimide and its derivatives to be used as the reactants in many chemical synthetic routes. Reportedly, such ring opening follows the concerted mechanism in methanol solvent, which, however, has an unreasonably high energy barrier (36.3 kcal mol−1 at the M06-2X/6-311++G(d,p) level of theory). By density functional theory calculations, we report that this ring opening prefers the alternatively stepwise mechanism. The stepwise mechanism has a much lower energy barrier (21.0 kcal mol−1 at the same level of theory) and thus is much more completive than the concerted one. The stepwise mechanism should be considered as the dominant mechanism responsible for the phthalimide ring opening when studying the kinetics of the relevant synthetic reactions in the future.

■ INTRODUCTION

ACS Paragon Plus Environment

The Journal of Physical Chemistry 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

Phthalimide and its derivatives are the precursors of anthranilic acids, which are widely used to synthesize useful organic compounds like azo dyes and saccharins.1-5 They have also been used to synthesize pharmaceutical molecules containing benzamides.6-9 Recently, Piou and Rovis have developed an elegant reaction methodology with N-enoxyphthalimides for the syn-carboamination of alkenes, in which N-enoxyphthalimides serve as the source of both C and N functionality and the Rh(III) complexes serve as the catalysts.10 Reportedly, the use of methanol as the solvent is critical to improve the efficiency of this carboamination reaction.10

Scheme1. The concerted (path 1) and stepwise (path 2) mechanisms for the opening of the phthalimide ring of N-enoxythalimide 1. Me, methyl.

To understand the underlying mechanisms responsible for the Rh(III)-catalyzed carboaminations, Liu and coworkers11 have computationally studied the reactions between N-enoxyphthalimides and alkenes with the presence of the Rh(III) compounds in methanol using density functional theory (DFT) calculations. Their results have provided detailed mechanisms for the carboamination processes and the atomistic-level insights into the stereospecifity of the reactions.10 However, according


Page 2 of 16

Page 3 of 16 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


to their results, the phthalimide group of N-enoxyphthalimide 1 follows the concerted ring opening mechanism (path 1 of Scheme 1), giving the open-ring compound 2 to further react with the alkenes to afford the final carboamination products.10 This concerted mechanism path 1 has an unreasonably high activation energy barrier (> 39.5 kcal mol−1 at the B3LYP/6-31(d,p) level of theory),12 which thus contradicts with the facile carboamination reaction experimentally observed at room temperature.10 The alternatively new ring opening mechanism with a lower energy barrier must exist to be responsible for the opening of the five-membered rings of the N-enoxyphthalimide 1.

Here, we will revisit the ring opening process of N-enoxyphthalimide using DFT calculations. We will report that N-enoxyphthalimide 1 prefers to follow the stepwise ring opening mechanism (path 2 of scheme 1) rather than the concerted mechanism path 1. The former has a much lower energy barrier than the latter (21.0 vs. 36.3 kcal mol−1 at the M06-2X/6-311++G(d,p) level of theory). Therefore, the stepwise mechanism is much more completive and should be considered as the dominant mechanism responsible for the ring opening of enoxyphthalimides when studying the kinetics of the relevant synthetic reactions in the future.10,13-18 ■ COMPUTATIONAL METHODS The ring opening mechanism of N-enoxyphthalimide 1 in methanol was explored by computationally optimizing the structures and calculating the energies for the possible intermediates and transition states involved in the reactions. All these calculations were conducted using the M06-2X functional19, 20 in conjunction with the 6-31G(d,p)



basis set21, 22 as implemented in the Gaussian 09 package.23 Reportedly, the M06-2X functional can more accurately calculate activation and reaction energies.24 Frequency analyses were done for all these optimized structures at the same level of theory, which confirmed that each intermediate and transition state had no and only one imaginary frequency, respectively. Single-point energy calculations were performed for some of the optimized structures at the M06-2X/6-311++G(d,p) level of theory to refine the total energies. Entropies and zero-point energies were obtained from the frequency calculations, which were then used to calculate the Gibbs free energies in combination with the total energies obtained from the single-point calculations. In all these calculations, the effects of solvents like methanol were considered using the polarizable continuum model.25, 26 ■ RESULTS AND DISCUSSION Concerted Mechanism. The concerted ring opening of N-enoxyphthalimide (path 1) has been recently studied by Liu and coworkers using the B3LYP/6-31G(d,p) method.11 To compare the energetics of the concerted and stepwise paths (paths 1 and 2) at the same level of theory, we calculated the Gibbs free energy profiles for both paths using the M06-2X/6-31G(d,p) method. It is known that the M06-2X functional can more accurately describe activation and reaction energies.24 Corresponding to the 1−ts1.1−2 transformation (i.e., path 1.1) in Figure 1, the concerted ring opening can be achieved by the addition of one methanol molecule to the phthalimide ring of 1, which encounters a high energy barrier of 42.1 kcal mol−1. The corresponding energy barrier calculated with the B3LYP/6-31G(d,p) method is 40.8 kcal mol−1, which is


Page 4 of 16

Page 5 of 16 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


comparable to that calculated here with the M06-2X/6-31G(d,p) method. Inspecting transition state structure ts1.1, this process consists of the formation of two new covalent bonds (the C−O bond between 1’s carbonyl C and the methanol’s O and the N−H bond between 1’s N and the methanol’s hydroxyl H) and the breaking of one old covalent bond (the methanol’s O−H bond). The formation of the N−H bond and the breaking of the O−H bond can be regarded as the H transfer from the O to the N.

Figure 1. The potential energy profiles for the concerted ring opening mechanism (path 1) of the phthalimide groups calculated at the M06-2X/6-31G(d,p) level of theory. The total energies (Gibbs free energies in parentheses) relative to the corresponding reactants are labeled. Paths 1.1, 1.2, and 1.3 correspond the ring opening processes assisted by one, two, and three methanol molecules, respectively; the extra one and two methanol molecules in paths 1.2 and 1.3 serve as the catalysts to transfer H atoms. The insert shows the structures of the reaction centers of the



transition states, in which the atomic distances closely relevant to the chemical bond rearrangements are labeled. The dashed circles designate the methanol molecules involved in the reactions. The unit of energy is kcal mol−1. Me, methyl.

The energy barrier of the concerted ring opening can be remarkably decreased when one or more methanol molecules participate into the reaction as the H-transfer catalysts, similar to the result reported by Liu and coworkers. The 1−ts1.2−2 transformation (i.e., path 1.2) in Figure 1 corresponds to the concerted opening of the phthalimide ring that is achieved by the addition of one methanol molecule to 1 with another methanol molecule as the H-transfer catalyst. Inspecting transition state structure ts1.2, methanol 1 passes its H to methanol 2, and methanol 2 passes its H to the N to complete the opening of the phthalimide ring, in which methanol 2 acts as the H-transfer catalyst. Similar to the case of the 1−ts1.2−2 transformation, methanols 2 and 3 act as the H-transfer catalysts in the 1−ts1.3−2 transformation (i.e., path 1.3). Paths 1.2 and 1.3 have lower energy barriers, which are 39.3 and 33.4 kcal mol−1, respectively, than that of path 1.1. However, the energy barriers of paths 1.2 and 1.3 are still too high to overcome at room temperature. The corresponding energy barriers for paths 1.2 and 1.3 calculated at the B3LYP/6-31G(d,p) level of theory are both above 39.5 kcal mol−1. Therefore, the M06-2X and B3LYP results consistently suggest that the concerted mechanism path 1 is unlikely the dominant mechanism responsible for the opening of the phthalimide ring.


Page 6 of 16

Page 7 of 16 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


The change in Gibbs free energy from 1 to 2 is −6.3 kcal mol−1 (Figure 1). Because extra methanol molecules are involved in the reaction paths, the formation of 2 via ts1.2 and ts1.3 needs some extra energy to remove the methanol molecules from the reaction system. The removal of these methanol molecules will be facile, because they bind with 2 through weak hydrogen bonds and their leaving is thermodynamically favorable (∆Gr = −4.6 kcal mol−1 when two methanols are removed, see Figure S1 of the supporting information, SI). Stepwise Mechanism. Our DFT calculations have suggested an alternatively stepwise mechanism path 2 for the phthalimide ring opening (Scheme 1), which has a much lower energy barrier than that of path 1 and thus is much more competitive. As shown in Figure 2, paths 2.1, 2.2, and 2.3 are the stepwise ring opening pathways. Each of these pathways consists of two steps: the first step is the nucleophilic addition of the methanol to the carbonyl C=O bond of the N-enoxyphthalimide 1, which doesn’t open the phthalimide ring; the second step is the ring opening process induced by transfer of the H atom from the hydroxyl O to the N atom. The difference among these three steps is that path 2.1 has no methanol molecules as the H-transfer catalysts, but paths 2.2 and 2.3 have extra one and two methanol molecules as the H-transfer catalysts, respectively. As shown in the insert of Figure 2, methanols 2 and 3 with dashed circles in transition state structures ts2.2, ts3.2, ts2.3, and ts3.3 are the methanol molecules as the H-transfer catalysts. The 1−ts2.1−int and int−ts3.1−2 transformations are the first and second steps of path 2.1, which have high energy barriers of 37.0 and 30.4 kcal mol−1, respectively. In contrast, the corresponding two energy barriers of path 2.2 are reduced to 20.6 and 26.1 kcal



mol−1, and those of path 2.3 are further reduced to 18.8 and 16.1 kcal mol−1. The rate-determining step of path 2.3 is the 1−ts2.3−int transformation with an energy barrier of only 18.8 kcal mol−1, suggesting path 2.3 to be the dominant mechanism responsible for the ring opening of the phthalimide ring.

To confirm the superiority of the stepwise mechanism path 2.3 over the concerted mechanism path 1.3, we performed single-point energy calculation with the M06-2X/6-311++G(d,p) method based on the geometries optimized with the M06-2X/6-31G(d,p) method. Figure 3 comparably shows the Gibbs free energy profiles calculated with the M06-2X/6-311++G(d,p) method for paths 1.3 and 2.3, which confirms that the energy barrier of path 2.3 is much lower than that of path 1.3 (21.0 vs. 36.3 kcal mol−1). The considerably low energy barrier of path 2.3 (i.e., 21.0 kcal mol−1 at the M06-2X/6-311++G(d,p) level of theory) suggests that this ring opening pathway is kinetically favorable, in agreement with the facile carboamination reaction between N-enoxyphthalimides and alkenes observed in the experiments at room temperature.10


Page 8 of 16

Page 9 of 16 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 2. The potential energy profiles for the stepwise ring opening mechanism (path 2) of the phthalimide groups calculated at the M06-2X/6-31G(d,p) level of theory. The total energies (Gibbs free energies in parentheses) relative to the corresponding reactants are labeled. Paths 2.1, 2.2, and 2.3 correspond the ring opening processes assisted by one, two, and three methanol molecules, respectively; the extra one and two methanol molecules in paths 2.2 and 2.3 serve as the catalysts to transfer H atoms. The insert shows the structures of the reaction centers of the transition states, in which the atomic distances closely relevant to the chemical bond rearrangements are labeled. The dashed circles designate the methanol molecules involved in the reactions. The unit of energy is kcal mol−1. Me, methyl.



Page 10 of 16

Figure 3. Gibbs free energy profiles of the concerted (path 1.3) and stepwise (path 2.3) ring opening pathways for the phthalimide group of N-enoxyphthalimide 1. The Gibbs free energies are obtained with single-point total energies calculated with the M06-2X/6-311++G(d,p) method and zero-point energies and entropies calculated with the M06-2X/6-31G(d,p) method. The unit of energy is kcal mol−1.

Reportedly, the use of methanol as the solvent is critical for the carboamination reaction.10 To understand the reason for the special ability of methanol in this ring opening process, we replaced methanol with two other molecules F3COH and H2O to examine how the energy barriers of path 2.3 (i.e., the most kinetically favorable ring opening pathway for methanol) varied with the solvents. Figure 4 comparably shows the reaction energy profiles for methanol, H2O, and F3COH, which correspond to the 1−ts2.3−int−ts3.3−2,

1−ts2.3′−int−ts3.3′−2,

and

1−ts2.3′′−int−ts3.3′′−2

transformations in the figure, respectively. As shown in Figure 4, the energy barriers of the rate-determining steps for F3COH, H2O and CH3OH are 26.5, 22.6, and 18.8 kcal mol−1, respectively. According to these energy barriers, their ability to open the phthalimide ring decreases in the order of CH3OH > H2O > CF3OH. Namely,


Page 11 of 16 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


methanol is the best among the three to open the phthalimide ring. This order agrees with the nucleophilicity27 order of methoxy (CH3O) > hydroxyl (HO) > trifluoromethoxy (CF3O), suggesting that solvent molecules with highly nucleophilic O-containing groups have the large ability to open the phthalimide rings. The favor of highly nucleophilic O-containing groups in the solvent molecules is consistent with the above stepwise ring opening mechanism path 2, in which the first step reaction is the nucleophilic addition of the O-containing groups of the solvent molecules to the electrophilic carbonyl bond (C=O) of the phthalimide ring. Figure S2 of the SI plots the LUMO of 1 (−1.50 eV) and HOMOs of CH3OH (−9.33 eV), H2O (−10.34 eV), and CF3OH (−11.95 eV). The orbital energy order for the HOMOs is CH3OH > H2O > CF3OH, in agreement with the nucleophilicity order of the O-containing groups of the three species. The larger nucleophilicity of the O-containing group will lead to the weaker bond strength of the O−H bond and thus the larger H-transfer ability. We considered two other phthalimide derivatives, saccharin and talmetoprim,28,29 to examine the applicability of the stepwise ring opening pathway (Table S1 of the SI). The rate-determining steps of both derivatives have Gibbs free energy barriers smaller than 24 kcal mol−1. Therefore, the stepwise mechanism may also be applicable to methanol assisted ring opening of other phthalimide derivatives. Therefore, the present results provide atomistic level insights into the critical role of methanol molecules in the carboamination reactions between N-enoxyphthalimides and ethenes. The methanol molecules have dual functions: the function as the addition reagents to induce the phthalimide ring opening and that as the catalyst to transfer H atoms. The



large nucleophilicity of the methoxy groups of methanols renders methanols the strong ability to open the phthalimide ring via the stepwise mechanism path 2.

F3COH

ts2.3' 22.6

ts3.3 16.1

th pa

CH3OH

ts3.3' 23.3

' 3' 2.

H 2O

ts3.3'' 30.4

ts2.3'' 26.5 th pa 3' 2.

18.8 ts2.3

th pa

3 2.

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 12 of 16

int'' 8.7

2'' 6.8

int' 0.4

0.0 1

2' 4.7

int 0.1

2 6.3 1.00 1.59 1.27 1

2

1.61 1.01 1.46

1.15 1.06

3

1

1.00 1.73

3 1.50 1.03 2

ts2.3'

2.27

2.00 1.81

ts2.3''

1.96 3

1.26

1.00 1.72 2 1.00

1.82

1.04

1.15

1.03 1

1.91

1.47 1.04 1 1.77

3

1.54

ts3.3'

0.98

2.06

0.99 2

ts3.3''

Figure 4. Gibbs free energy profiles of the stepwise ring opening mechanisms (paths 2.3, 2.3′, 2.3′′) calculated with the M06-2X/6-31G(d,p) method. In paths 2.3, 2.3′, 2.3′′, the phthalimide ring openings are assisted with CH3OH, H2O, and F3COH, respectively. The insert shows the structures of the reaction centers of the transition states, in which the atomic distances closely relevant to the chemical bond rearrangements are labeled. The dashed circles designate the solvent molecules involved in the reactions. The unit of energy is kcal mol−1. ■ CONCLUSION The mechanisms responsible for the opening of the phthalimide rings of N-enoxyphthalimides in methanol solvent have been studied by DFT calculations.


Page 13 of 16 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


Besides the concerted ring opening mechanism path 1, which is already reported before, our calculations disclose the stepwise mechanism path 2 (Scheme 1). Both mechanisms consistently predict that the opening of the phthalimide ring is induced by

the

addition

of

the

methanol

molecule

to

the

carbonyl

bond

of

N-enoxyphthalimide, and that the participation of two extra methanol molecules in this process as H-transfer catalysts greatly reduce the energy barriers. However, the stepwise mechanism with two methanol molecules as H-transfer catalyst (path 2.3) is much more competitive than the corresponding concerted mechanism path 2.1 (Figure 4). Therefore, the stepwise mechanism should be considered as the dominant mechanism responsible for the opening of the phthalimide rings when studying the kinetics of the relevant synthetic reactions in the future. The importance of H transfer in the ring opening process suggests that other molecules with potential H-transfer ability, if any in the reaction system, may also contribute to the ring opening and need to be considered when studying the ring opening mechanism.

■ ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: xx.xxxx/acs.jpca.xxxxxxx.

Full citation of Refs. 8 and 18 and Cartesian coordinates of all optimized structures (PDF)



■ AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] (X.J.G.); [email protected] (X.G.)

ORCID Xingfa Gao: 0000-0002-1636-6336, Xuejiao J. Gao: 0000-0002-0643-9319

Notes The authors declare no competing financial interest. ■ ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China (NSFC) Project (No. 21773095). ■ REFERENCES (1) Choi, J.-H.; Lee, H.-Y.; Towns, A. D. Dyeing Properties of Novel Azo Disperse Dyes Derived from Phthalimide and Color Fastness on Poly(lactic acid) Fiber. Fiber. Polym. 2010, 11, 199. (2) Castro-Godoy, W. D.; Oksdath-Mansilla, G.; Arguello, J. E.; Penenory, A. B. Exploring the Photophysical and Photochemical Properties of N-(Thioalkyl)-Saccharins as an Alternative Route to the Synthesis of Tricyclic Sultams. J. Org. Chem. 2017, 82, 101. (3) Koh, J.; Kim, H.; Park, J. Synthesis and Spectral Properties of Phthalimide Based Alkali-Clearable Azo Disperse Dyes. Fiber. Polym. 2008, 9, 143. (4) Maatz, G.; Ritter, H. Transparent Hydrophilic Materials Containing Covalently Attached Phthalimide Azo Dyes. Macromol. Chem. Phy. 2012, 213 , 1569. (5) Dang, Y.; Deng, X.; Guo, J.; Song, C.; Hu, W.; Wang, Z.-X. Unveiling Secrets of Overcoming the “Heteroatom Problem” in Palladium-Catalyzed Aerobic C–H Functionalization of Heterocycles: A DFT Mechanistic Study. J. Am. Chem. Soc. 2016, 138, 2712. (6) Tran, B. L.; Li, B.; Driess, M.; Hartwig, J. F. Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes. J. Am. Chem. Soc. 2014, 136, 2555. (7) DeGlopper, K. S.; Fodor, S. K.; Endean, T. B. D.; Johnson, J. B. Decarbonylative Cross Coupling of Phthalimides with Diorganozinc Reagents-Efforts toward Catalysis. Polyhedron 2016, 114, 393.


Page 14 of 16

Page 15 of 16 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


(8) Maugeri, C.; Alisi, M. A.; Apicella, C.; Cellai, L.; Dragone, P.; Floravanzo, E.; Florio, S.; Furlotti, G.; Mangano, G.; Ombrato, R.; et al. New Anti-Viral Drugs for the Treatment of the Common Cold. Bioorgan. Med. Chem. 2008, 16, 3091. (9) Havlik, S. E.; Simmons, J. M.; Winton, V. J.; Johnson, J. B. Nickel-Mediated Decarbonylative Cross-Coupling of Phthalimides with in Situ Generated Diorganozinc Reagents. J. Org. Chem. 2011, 76, 3588. (10) Piou, T.; Rovis, T. Rhodium-catalysed Syn-carboamination of Alkenes via A Transient Directing Group. Nature 2015, 527, 86. (11) Xing, Y.-Y.; Liu, J.-B.; Sheng, X.-H.; Sun, C.-Z.; Huang, F.; Chen, D.-Z. Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed Carboamination/Cyclopropanation Reactions between N-Enoxyphthalimides and Alkenes. Inorg. Chem. 2017, 56, 5392. (12) The authors of Ref. 11 have treated these high activation energy barriers using the Whitesides method to make them comparable with the experiment of Ref. 10; see Ref. 11 for the details of the Whitesides method. (13) Weinstein, A. B.; Ellman, J. A. Convergent Synthesis of Diverse Nitrogen Heterocycles via Rh(III)-Catalyzed C-H Conjugate Addition/Cyclization Reactions. Org. Lett. 2016, 18, 3294. (14) Hyster, T. K.; Rovis, T. An Improved Catalyst Architecture for Rhodium (III) Catalyzed C-H Activation and its Application to Pyridone Synthesis. Chem. Sci. 2011, 2, 1606. (15) Piou, T.; Rovis, T. Rh(III)-catalyzed Cyclopropanation Initiated by C-H Activation: Ligand Development Enables a Diastereoselective [2 + 1] Annulation of N-enoxyphthalimides and Alkenes. J. Am. Chem. Soc. 2014, 136, 11292. (16) Webb, N. J.; Marsden, S. P.; Raw, S. A. Rhodium(III)-catalyzed C-H Activation/Annulation with Vinyl Esters as an Acetylene Equivalent. Org. Lett. 2014, 16, 4718. (17) Guimond, N.; Gorelsky, S. I.; Fagnou, K. Rhodium(III)-catalyzed Heterocycle Synthesis Using an Internal Oxidant: Improved Reactivity and Mechanistic Studies. J. Am. Chem. Soc. 2011, 133, 6449. (18) Liu, B.; Song, C.; Sun, C.; Zhou, S.; Zhu, J. Rhodium(III)-Catalyzed Indole Synthesis Using N-N Bond as an Internal Oxidant. J. Am. Chem. Soc. 2013, 135, 16625. (19) Zhao, Y. T., 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. (20) Zhao, Y. T., Truhlar, D. G. Acc., Density Functionals with Broad Applicability in Chemistry. Chem. Res. 2008, 41, 157. (21) Hariharan, P. C.; Pople, J. A. The Influence of Polarization Functions on Molecular Orbital Hydrogenation Energies. Theor. Chim. Acta 1973, 28, 213.



(22) Hehre, W. J. M.; Ditchfield, R.; Pople, J. A. Self-Consistent Molecular Orbital Methods. XII. Further Extensions of Gaussian-Type Basis Sets for Use in Molecular Orbital Studies of Organic Molecules. J. Chem. Phys. 1972, 56, 2257. (23) 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.; et al. Gaussian 09; Gaussian, Inc.: Wallingford, CT, 2009. (24) James, N. C.; Um, J. M.; Padias, A. B.; Hall, H. K., Jr.; Houk, K. N. Computational Investigation of the Competition between the Concerted Diels-Alder Reaction and Formation of Diradicals in Reactions of Acrylonitrile with Nonpolar Dienes. J. Org. Chem. 2013, 78, 6582. (25) Miertuš, S. T. Approximate Evaluations of The Electrostatic Free Energy and Internal Energy Changes in Solution Processes. J. Chem. Phys. 1982, 65, 239. (26) Miertuš, S.; Scrocco, E.; Tomasi, J. Electrostatic Interaction of a Solute With a Continuum. A Direct Utilizaion of AB Initio Molecular Potentials For The Prevision of Solvent Effects. J. Chem. Phys. 1981, 55, 117. (27) Ingold, C. K. Significance of Tautomerism and of the Reactions of Aromatic Compounds in the Electronic Theory of Organic Reactions. J. Chem. Soc.; 1933, 1120. (28) Behrens, M.; Blank, K.; Meyerhof, W., Blends of Non-caloric Sweeteners Saccharin and Cyclamate Show Reduced Off-Taste due to TAS2R Bitter Receptor Inhibition. Cell Chem. Biol. 2017, 24, 1199-1204. (29) Kumar, P.; Dasari, S.; Patra, A. K., Ruthenium(II) Complexes of Saccharin with Dipyridoquinoxaline and Dipyridophenazine: Structures, Biological Interactions and Photoinduced DNA Damage Activity. Eur. J. Med. Chem. 2017, 136, 52-62.

TOC Graphic


Page 16 of 16

Methanol-Assisted Phthalimide Ring Opening ... - ACS Publications

Recommend Documents