DFT Mechanistic investigation into BF3-catalyzed alcohol oxidation by

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DFT Mechanistic investigation into BF3-catalyzed alcohol oxidation by a hypervalent iodine(III) compound Kaveh Farshadfar, Antony Chipman, Brian F Yates, and Alireza Ariafard ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b01599 • Publication Date (Web): 06 Jun 2019 Downloaded from http://pubs.acs.org on June 7, 2019

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ACS Catalysis

DFT Mechanistic Investigation into BF3-Catalyzed Alcohol Oxidation by a Hypervalent Iodine(III) Compound Kaveh Farshadfar,† Antony Chipman,§ Brian F. Yates,§ Alireza Ariafard*§,† †Department of Chemistry, Islamic Azad University, Central Tehran Branch, Poonak, Tehran, Iran §School of Physical Science (Chemistry), University of Tasmania, Private Bag 75, Hobart, TAS 7001, Australia

Abstract Density functional theory (DFT) at the SMD/M06-2X/def2-TZVP//SMD/M06-2X/LANL2DZ,631G(d) level was employed to explore mechanistic aspects of BF3-catalysed alcohol oxidation using a hypervalent iodine(III) compound, [ArI(OAc)2], to yield aldehydes/ketones as the final products. The reaction is composed of two main processes; (i) ligand exchange and (ii) the redox reaction. Our study for 1-propanol discovered that ligand exchange is preferentially accelerated if BF3 first coordinates to the alcohol. This coordination increases the acidity of the alcohol hydroxyl proton, resulting in ligand exchange between the iodane and the alcohol proceeding via a concerted interchange associative mechanism with an activation free energy of ~10 kcal/mol. For the redox process, the calculations rule out the feasibility of the conventional mechanism (alkoxy Cα deprotonation) and introduce a replacement for it. This alternative route commences with αhydride elimination of the alkoxy group promoted by BF3 coordination, which yields a BF3stabilized aldehyde/ketone product and iodane [ArI(OAc)(H)]. The ensuing iodane is extremely reactive toward reductive elimination to give ArI + HOAc in a highly exergonic fashion (ΔG = 62.1 kcal/mol). The reductive elimination reaction is the thermodynamic driving force for the 1 ACS Paragon Plus Environment

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alcohol oxidation to be irreversible.

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Consistent with the kinetic isotope effect reported

experimentally, the α-hydride elimination is calculated to be the rate-determining step with an overall activation free energy of ~24 kcal/mol.

Keywords: DFT calculations, Reaction mechanism, Alcohol oxidation, Hypervalent iodine(III), BF3 catalyst, Hydride shift

Introduction Hypervalent iodine(III) compounds have attracted much attention as oxidants in organic synthesis as they can be a replacement for transition metals with the advantage of having environmentally benign properties.1-18 Although iodine(III) reagents are competent to conduct many organic transformations, addition of a Lewis acid such as BF3 is often a prerequisite for a process to occur. For example, it has been shown that an iodine(III) reagent in conjunction with BF3.Et2O considerably accelerates the processes that yield λ3-diaryliodanes,12 olefin diacetoxylation19 and a plethora of other products.19-35 In this context, Ochiai et al. reported that alcohols can be selectively oxidized by hypervalent iodine(III) compound 2 to aldehydes or ketones in the presence of BF3.Et2O as the catalyst (Scheme 1).36 For this catalytic reaction, the first step is proposed to be a ligand exchange between iodine(III) reagent 2 and the alcohol, followed by a redox process to give the final product. It was experimentally demonstrated by Ochiai et al. that the BF3 Lewis acid participates in accelerating both the ligand exchange and redox steps. To account for the role of the BF3 in the redox process, the formation of intermediate 6 has been postulated (Scheme 1). In this case, the BF3 coordination converts the acetate into a strong leaving group, thereby promoting the redox step by deprotonation of the alkoxy Cα hydrogen. Using a kinetic isotope effect analysis, 2 ACS Paragon Plus Environment

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ACS Catalysis

Ochiai et al. suggested that the alkoxy Cα deprotonation is the rate-determining step of this redox process. O 2N OH H R'

AcO

R''

1 proposed mechanism:

I

OAc

BF3 cat.

R''

R'

2 BF3

(ii) redox step promoted by  C -deprotonation O 2N

O 2N

R'' R'_

BF3 O

I 4

3

AcOH

(i) ligand exchange step

H

O 2N

O

I 5

OAc

H R'' R'_

I

O

F 3B 6

O

O

Scheme 1. A reaction scheme showing BF3-catalysed alcohol oxidation by an iodine(III) reagent which occurs at 30 oC over 4 hours where the alcohol substrate was used in vast excess. The proposed mechanism for such a redox process is provided below the reaction. Although a plausible mechanism of this alcohol oxidation has already proposed and highlighted in several important reviews,1,11,37 many questions are yet to be addressed. For example, it is not very clear how BF3 facilitates the ligand exchange process. Scheme 2 represents one possible mechanism of ligand exchange occurring through transformation 7  8  9. According to this proposal, 7 undergoes isomerization to 8 which generates an empty site in the cis position to the phenyl ring in the λ3-iodane. The open site can then be occupied by the nucleophile Nu-H to provide suitable conditions for the proton transfer from Nu-H to the acetate trans to the phenyl ring. It is expected that the ease of the ligand exchange process depends upon the energy of intermediate 8 relative to 7; the lower the energy of intermediate 8, the more energetically 3 ACS Paragon Plus Environment

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accessible the ligand exchange reaction. In this context, Lledós and Shafir et al. showed that coordination of BF3 to 7 satisfies this situation and causes the isomerization to proceed much more smoothly and therefore species 11 become more available for Nu-H coordination.38 The question is whether a similar protocol to the one proposed by Lledós and Shafir et al. operates to accelerate the ligand exchange between 1 and 2 or if the reaction proceeds through a hitherto unknown mechanism. To realize this, we have comprehensively studied such a ligand exchange in the presence of the BF3 catalyst with the aim of providing a new insight into this essential step.

Nu-H O

I

O O

O

7

I

O

O

O

O

I

Nu H

O

O

8

O O 9

BF3

Nu-H O

I

O

O F 3B

O

10

I O

O

O 11

Nu

O

BF3

I

O

H O

O

BF3

O

12

Scheme 2. Plausible mechanisms for ligand exchange in absence and presence of BF3. As discussed above (Scheme 1), once alkoxy intermediate 5 is formed, a BF3 coordinates to afford intermediate 6 which is postulated to be highly reactive toward a redox process. According to the Ochiai’s mechanism (Scheme 1), for reduction from 6 to take place, deprotonation of the alkoxy Cα hydrogen by an appropriate base is a prerequisite. This is very similar to the mechanism for 4 ACS Paragon Plus Environment

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ACS Catalysis

alcohol oxidation by 2-iodoxybenzoic acid (IBX) proposed by Goddard III et al.39 and subsequently modified by Schaefer III et al.40 (Scheme 3). On that basis, when ligand exchange occurs between IBX and the alcohol, alkoxy intermediate 13 is produced. This iodine(V) intermediate undergoes isomerization to 14 in which the oxo group is positioned trans to the carboxylate functional group. They reported that the oxo group serves as a base and deprotonates the alkoxy Cα hydrogen, resulting in alcohol oxidation and iodine(V) reduction to iodine(III). In the case of IBX, an oxo group acts as an internal base, but in the case of iodine(III), no such internal base is available. The question now is whether the BF3-bound acetate acts as the base or another alcohol is responsible for conducting the redox process. Alternatively, the alcohol oxidation by iodine(III) may proceed through a different mechanism that is yet to be revealed for the scientific community. In this contribution, we intend to disclose the role of BF3 in accelerating both the ligand exchange and redox steps for alcohol oxidation by using iodane 2.

O

O O R

'

R''

O H

I

isomerisation

O

O 13

O R' R

''

O H

I

deprotonation (redox step)

O R

'

R''

O 14

O H

I O TS1

Scheme 3. The key steps for alcohol oxidation by a hypervalent iodine(V) reagent (IBX) proposed by Goddard III et al.

Results and Discussion To explore the role of BF3 in accelerating each of the primary steps of the alcohol oxidation using iodane 2, we have divided our discussion into two distinct sections: ligand exchange and redox process. 5 ACS Paragon Plus Environment

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Ligand exchange. Although various possibilities are likely, our calculations have allowed us to propose three different mechanisms for ligand exchange between the alcohol and the iodine(III) reagent which is assigned in Scheme 4 as (i) isomerization-associative mechanism (pathway A), (ii) stepwise interchange associative mechanism (pathway B); and, (iii) concerted interchange associative mechanism (pathway C). Pathway A is characterized by initial isomerization of 2 to 15, then alcohol coordination, and finally deprotonation of the coordinated alcohol by the acetate ligand trans to the aryl ring in 16. Pathway B initiates via four coordinate transition structure TS2-18 in which the alcohol acts as an entering group while acetate leaves the coordination sphere. This ligand exchange leads to adduct 18, which is reactive toward forming acetic acid. The bonding of this four coordinate transition structure can be described as 4-centre 6electron (4c-6e) wherein the empty p orbital of the iodine(III) center simultaneously interacts with the lone pairs of the alcohol and the two OAc ligands. This situation is provided by the interaction of an alcohol lone pair with primarily the LUMO of structure 2. Pathway C is somehow similar to pathway B with the difference that both the substitution and the proton transfer occur simultaneously via transition structure TS2-17.

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A: isomerization-associtive

I

O O

H

NO2

NO2

NO2

NO2

O

I

O O

O

O

O

O

H

O

2

O

I

O

O

O

15

I

O

O O

0.5 (HOAc)2

17

16

B: stepwise interchange associtive NO2

H

NO2

O

NO2

O

NO2

O O

I

O

H

O

O

O

H

O

I

O

O

2

I

O

O

O O

TS2-18

O

I

0.5 (HOAc)2

O O

17

18

C: concerted interchange associtive NO2

O

I

O

O O

2

H

NO2

NO2

O

O

O H

O

I

O

O O

TS2-17

0.5 (HOAc)2

I

O O

17

Scheme 4. Three possible mechanisms found by DFT calculations for the ligand exchange process On the basis of the three pathways illustrated in Scheme 4, we commenced our investigation by calculating the ligand exchange process between hypervalent iodine(III) reagent 2 and propanol in the absence of BF3. In this case, any attempt to find pathway B collapsed to pathway C. Figure 1 compares the energy profiles assigned to pathways A and C for the ligand exchange process. From this comparison, it is inferred that the two pathways are almost isoenergetic with pathway C being 0.6 kcal/mol lower in energy than pathway A. This result is consistent with our recent study wherein the ligand exchange between a phenol and phenyliodine(III) diacetate (PIDA) was reported to preferentially proceed via pathway C.41 In pathway A, transition structure connecting


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16 to 17 is not located due to the high basicity of the acetate anion which spontaneously deprotonates the alcohol stabilized by the iodine(III) center. NO2

NO2

O O

H O

I

I

O O

O

TS2-18

O O TS 2-15

21.3

21.8

O

NO2

TSa 21.9 OH O H 18.1

OH

NO2

I

H I

O

19

O

O

O

O

O

TS16-17

O

I

O

H O

0.5 (HOAc)2

O

O 16

0.5 (HOAc)2

0.2

0.2

0.0 NO2

NO2

O

O

O

O

15

3.4

O

15.4 NO2

NO2

O O

O

I

I

O

O

I

17

O

O

2

pathway C

NO2

O

O O

I

O

17

O

pathway A

Figure 1. Free energy profile for ligand exchange between iodane 2 and 1-propanol occurring via pathways A and B.42 The relative free energies are given in kcal/mol. The relative Gibbs energy of TSa is estimated based on the methodology proposed by Hall and co-workers.43 Now, we turn our attention to the question of how the BF3 addition accelerates the ligand exchange process. To commence, we must first determine with which substrate (alcohol or iodane) BF3.Et2O energetically prefers to interact. To this end, two SN2-type transition structures TS20 and TS2-21 were located (Figure 2). The calculations show that TS20 is about 2.6 kcal/mol lower in energy than TS2-21, which suggests that BF3 should preferentially coordinate to the alcohol and not the iodane; the BF3 coordination to the alcohol was calculated to be exergonic by about -3.6 kcal/mol. 8 ACS Paragon Plus Environment

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ACS Catalysis

Our calculations suggest that formation of 20 is less likely to proceed via an SN1-type reaction due to the finding that TSb lies 4.1 kcal/mol higher in energy than TS20 (Figure 2). BF3 + Et2O

9.6 NO2

NO2

O O F3B

I

21 -4.5

O O

O Et2O

I

O O

O F O

B F

NO2

O O

I 2

O

TSb 20.7 OH

O BF3.Et2O

F

TS2-21 19.2

0.0

O H F O

B F

F

BF3

Et2O

O

TS20 16.6

20 -3.6

Figure 2. The calculated mechanism for coordination of BF3 to either the alcohol or iodane 2. The relative free energies are given in kcal/mol. The relative free energy of TSb is estimated based on the methodology proposed by Hall and co-workers.43 Once 20 is formed, it has the potential to initiate the ligand exchange reaction. Our results show that the ligand exchange in this case proceeds through pathway C after surmounting an energy barrier as low as 9.8 kcal/mol; efforts to find the vital transition structure of pathway B is invariably collapsed to pathway C (Figure 3). It follows from this result that the ligand exchange between the BF3.PrOH adduct and the iodane occurs much faster than the same process does between PrOH and the iodane. This acceleration can be explained based on the higher acidity of the O-H protons in the BF3.PrOH adduct than in free PrOH. Indeed, coordination of the Lewis acid BF3 to the alcohol makes the hydroxyl proton more labile, thereby facilitating the ligand exchange.


H

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Figure 3. Free energy profile for ligand exchange between iodane 2 and BF3.1-propoanol occurring via pathway C. Relative free energies are given in kcal/mol. The selective bond distances in DFT-calculated structures TS22-23, 2 and 23 are given in Å. Although, as established above, BF3 prefers coordinating to the alcohol, we also investigated the possibility in which the ligand exchange is commenced by coordination of BF3 to the iodane. In this case, the ligand exchange was found to occur via pathways A or B (Figure 4); the reduced basicity of the ligand in BF3.OAc results in the ligand exchange taking place through pathway B and not C.44 All the key transition structures associated with pathways A and B (Figure 4) were calculated to lie far above TS22-23 (Figure 3). Such a result suggests that the BF3 coordination to the alcohol likely provides access to the most favorable pathway for ligand exchange.45


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ACS Catalysis

Notably, all previous reports have demonstrated that for a particular reaction to be catalyzed by a Lewis or Brønsted acid, the acid should be added to the iodane reagent.40, 46-52 By contrast, in this study, we have discovered that addition of BF3 to the alcohol (and not the iodane) best facilitates the ligand exchange. This finding shows that addition of the acid to the iodane is not always a prerequisite for a process to be accelerated, but that sometimes an acid catalyst can directly activate an organic substrate to promote a given reaction in the presence of an iodane. NO2 NO2

F 3B NO2

O

O NO2

O O

I

O

TSe

O

15.2

H

O

O

I

O

HO

I

O O

O

BF3

TSd

TS21-25

O

10.2

I

H O

BF3

F 3B

TS27-28

O

TSc 15.9

O O

NO2

O

BF3

O

I

O O

O

O O

F 3B

O

H

NO2

H

I

12.2

OH

10.1

O

O

O

TS21-27

OH

BF3

O

HO O

7.4

5.0

BF3

NO2 2.9

2.4 NO2

NO2

O O

I 17

O O

O O

I

O

28

O

I O

F 3B O

H

2.4

NO2

0.6

F 3B

I

NO2

O O BF3

O -4.5 O

O

O

-1.6 NO2

25 NO2

27

O O

I

O

21

O O

I

O

O

O BF3

H O

F 3B pathway B

O

I 17

O O

26

pathway A

Figure 4. Free energy profile for ligand exchange between 1-propanol and iodane 21 occurring via pathways A and B. The relative free energies are given in kcal/mol. The relative free energies of TSc and TSd are estimated based on the methodology proposed by Hall and co-workers.43

Redox process based on the conventional mechanism. As illustrated in Figure 3, the most favorable pathway for ligand exchange affords intermediate 24 in which BF3 is coordinated 11 ACS Paragon Plus Environment

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directly to the oxygen atom of the alkoxy ligand. In the literature, it was proposed that for the redox to occur, BF3 must coordinate, not to the alkoxy, but to the OAc ligand (Scheme 1). This mode of coordination should render the OAc as a good leaving group and increase the cathodic reduction potential of the iodine(III) center to promote the redox step via deprotonation of the alkoxy Cα hydrogen. Our calculations show that 24 and 21 are almost isoenergetic (Figure 5), which probably means that the formation of 21 is not impossible. However, our calculations show that, in contrast to the expectation, structure 21 is extremely unreactive toward the redox process. The various transition structures (all in blue) illustrated in Figure 5 confirm this claim. The Cα hydrogen is anticipated to be deprotonated by an available base such as BF3.OAc or another alcohol. Starting from 21, four transition structures, which consider these bases as the deprotonating agent are calculated (TS21, TSʹ21, TS31, and TSʹ31). We found that these saddle points are too high in energy to be accessible under the reaction conditions; the activation energies span a range from 34.5 kcal/mol for TS31 to 40.2 kcal/mol for TSʹ31.


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ACS Catalysis

NO2

I

NO2

H O BF3

H O

NO2

O

NO2

F3B I

O

I

H O

F 3B

H

O

60.5

O O F 3B

H O

TS'24

TS'21

43.0

31.3 H O

NO2 NO2

BF3 (PrOH)2

I

O

O BF3

O

O

(PrOH)2

H O H

I

TS24

F 3B

O

BF3

51.3

H O NO2

O

I

O

O

TS'29

O

H

BF3.Et2O

O

O F 3B

29

I

O

I

O

O

TS21

F 3B

21

F 3B

30.1

-6.8

-6.7

O

O

O 24

H O H

(PrOH)2

O

O

Et2O

-4.0

41.0

NO2

BF3 I

O

TS29

NO2

O O

Et2O

O

NO2

BF3.Et2O

F 3B NO2

O F 3B

NO2

NO2

I

O

BF3 I

H

O

O O

30 12.8

I

I

O

F 3B

17

31

2.4

-0.1

(PrOH)2

NO2

H I

BF3 40.6

33.4

H O

O O

H

O TS30

O

NO2

O H O

O

TS'31 (PrOH)2

NO2 H

O

I

I

O

O

47.0

H O H

H O

TS17

NO2

O

I

O

TS'17

TS31

40.7

27.7

Figure 5. The calculated mechanism for the redox step via Cα hydrogen deprotonation starting from intermediates 17, 21, 24 and 29.53 The relative free energies are given in kcal/mol. Our calculations led us to conclude that, in contrast to the proposed mechanism in the literature, 21 is unreactive toward the redox process. To discover whether redox via Cα deprotonation might proceed from other intermediates, species 24, 17 and 29 are considered as candidates for initiating the reaction. We found that structure 17, which does not feature any BF3 catalyst, is extremely unreactive toward the redox process; in this case, overall activation barriers through transition structures TS17 and TSʹ17 are calculated to be highly energy consuming (>45 kcal/mol). Such high barriers confirm the importance of BF3 in facilitating the redox process. Structure 24, which has BF3 on the alkoxy ligand was also found to be unreactive toward a redox process via Cα deprotonation. Indeed, the presence of BF3 on the alkoxy group reduces the ability of its oxygen 13 ACS Paragon Plus Environment

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atom to transmit two electrons to iodine(III), thereby diminishing the potency of the alkoxy as a reductant. Finally, we found that the addition of two BF3 to 17 to give structure 29 makes the redox even less likely; all activation barriers were calculated to be greater than 45 kcal/mol.

Redox process uncovered by DFT calculation. All the evaluations undertaken above have brought us to the conclusion that the alcohol oxidation cannot occur through the conventional mechanism. This prompted us to seek an energetically more accessible pathway for alcohol oxidation. Interestingly, we found that alcohol oxidation in this system is most likely to proceed via alkoxy α-hydride elimination and not via the Cα deprotonation. The iodine(III) center has the ability to receive a hydride from the alkoxy ligand facilitated by BF3 coordination. The energy profile for this novel mechanism is outlined in Figure 6a. Accordingly, the aldehyde formation process starts by isomerization of 24 to α-agostic iodane 32 via transition structure TS24-32. The ensuing intermediate gains some stability through an agostic interaction and is susceptible to be converted to iodane 33 by hydride abstraction concomitant with the ejection of the BF3-stabilized aldehyde product. Once intermediate 33 is formed, it can undergo a very facile reductive elimination through the two transition structures designated in Figure 6a as TS33-34 and TS34-35 with an activation barrier as low as 3.1 kcal/mol. The overall activation barrier of our novel mechanism for producing the aldehyde (23.4 kcal/mol) falls far beneath those of the traditionally accepted mechanisms discussed in Scheme 1 and calculated in Figure 5. The nature of hydrogen transfer is evaluated by investigating the antibonding orbital relating to the 3-centre 4-electron (3C-4e) bond of species TS24-32, TS32-33, and 33. As shown in Figure 6b, the energy of this antibonding orbital raises from -2.6 (for TS24-32) to -2.1 (for TS32-33) and then to 1.6 eV (for 33). This increase in energy can be explained by the fact that the hydrogen is transferred 14 ACS Paragon Plus Environment

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ACS Catalysis

as a hydride. Indeed, since a hydride acts as a strong σ donor ligand, the repulsive interactions in the corresponding antibonding orbital becomes more significant as the hydride transfer is being progressed. The NBO charge on the iodine center becomes less positive from TS24-32 (1.54) to TS32-33

(1.28) and then to 33 (1.04), further supporting the relevant hydrogen is transferred as a

hydride. The isomerization from 33 proceeds with an activation barrier as low as 3.1 due to the presence of the hydride ligand positioned trans to the acetate ligand. Indeed, the hydride ligand with the strong trans influencing property causes the I-O bond in 33 to be weakened, leading to the acetate ligand to be more prone to change its position. This statement is supported by the longer I-O bond distances in 33 (2.419 Å) than in 2 (2.130 Å). The less reactivity of 2 toward isomerization (Figure 1) is related to the fact that two acetate ligands with relatively weak trans influencing properties are bounded more strongly to the iodine center. It follows that the I-OAc bond strength plays a crucial role in determining the ease of the corresponding isomerization; the weaker the I-OAc bond, the easier the isomerization.


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Figure 6. (a) Free energy profile for aldehyde formation starting from intermediate 24 via αhydride elimination. The relative free energies are given in kcal/mol. (b) Spatial plots of the antibonding orbitals associated with the 3C-4e bond in species 24, 33 and TS32-33. The selective bond distances in DFT-calculated structures 24, 33 and TS32-33 are given in Å. Intermediate 32 is impossible to be located due to the flatness of the potential energy surface in vicinity of the transition structure TS24-32.


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To find out the role of BF3 in stabilizing the transition structure of α-hydride elimination, TS′32 was calculated (Figure 7). This transition structure was found to be highly energetic (48.8 kcal/mole), which highlights the potency of BF3 as a catalyst in lowering the overall activation energy. In fact, BF3 coordination weakens the I-O (alkoxy) bond in 24, which in turn facilitates the isomerization step necessary for aldehyde formation. This assertion is further supported by calculating transition structure TS′′32 in which BF3 coordinates to the acetate and not the alkoxy ligand. The energy computed for this transition structure (62.6 kcal/mol) is even higher than that of TS′32, which proves that for the α-hydride elimination mechanism to operate, BF3 coordination to the alkoxy ligand is a prerequisite. We found that a correlation exists between I-O(alkoxy) bond distance and the activation barrier to α-hydride elimination; the shorter the I-O(alkoxy) bond, the higher the activation energy (Figure 7). This energetic trend means that the I-O(alkoxy) bond strength is the key determinant for setting the ease of the process leading to formation of aldehyde/ketone. NO2

2.193 A

NO2

2.007 A

NO2

1.970 A

F3B I

O

24

O

O

O

-6.7

I

O

17 2.4

O

NO2 H

H

I

O BF3

I

O

21 -6.8

O

NO2 H

O O

O

H

I

NO2 H

O

O

O

BF3

H

I

O

O O

TS32-33

TS'32

TS''32

17.1

48.8

62.6

BF3


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Figure 7. Calculation transition structures for α-hydride elimination starting from intermediates 24, 17 and 21. The relative free energies are given in kcal/mol.

Catalytic cycle proposed by DFT calculation. Figure 8 summarizes our finding for BF3 catalyzed alcohol oxidation by a hypervalent iodine(III) reagent. As illustrated, the catalytic cycle commences with a substitution reaction between the alcohol and BF3.Et2O to form active catalyst 20. Then, the ligand exchange between 20 and iodane 2 occurs through the concerted interchange associative mechanism to afford intermediate 24 via transition structure TS22-23. This intermediate is susceptible to undergo α-hydride elimination by crossing transition structure TS32-33 to yield BF3-stabilized aldehyde product and iodane 33. The ensuing iodane is extremely reactive toward the reductive elimination of acetic acid in an exergonic fashion. The BF3.alcohol active catalyst is finally regenerated though a reaction between a free alcohol and the BF3-stabilized aldehyde.54 The rate-determining step of this process, where the alcohol is propanol, is calculated as 23.4 kcal/mol, which was assigned to transition structure TS32-33. This result is fully consistent with a large kinetic isotope effect observed experimentally which demonstrated that the cleavage of alkoxy Cα-hydrogen bond occurs in the rate-determining step. A unique feature of our proposed catalytic cycle is that reduction of the iodine(III) center takes place after formation of the product and is an off-cycle process; usually, for the reactions conducted by an iodane, iodine(III) reduction coincides with product formation.55-60


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ACS Catalysis

BF3.Et2O OH NO2 O BF3 O OH

H

O

I

O

2

O O

20

HOAc

NO2

NO2 O I O O H O BF3 O

BF3

I

O

TS22-23

NO2

H

I 33

NO2

O

NO2

O H

F3B O

H

O BF3

I

O O

I

O

24

O

TS32-33

Figure 8. Catalytic cycle for BF3-catalysed alcohol oxidation by iodane 2 discovered through DFT calculation.

At the closure of this section, we wish to note that although both iodine(III) and iodine(V) hypervalent compounds are capable of oxidizing alcohols, they follow distinct oxidation mechanisms; oxidation by iodine(III) compounds occurs through the α-hydride elimination of alkoxy group (introduced in the present work), whereas by iodine(V)39, 40 through Cα-hydrogen deprotonation (conventional mechanism). This disparity might relate to two factors which increase 19 ACS Paragon Plus Environment

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affinity of iodine(V) for the conventional mechanism: (i) an iodine(V) compound has an internal base (oxo ligand) available to serve as a deprotonating agent (Scheme 3) and (ii) an iodine(V) center has higher electron deficiency than an iodine(III), resulting in its Cα hydrogen being more acidic. Oxidation of secondary alcohols by iodane 2. Ochiai et al. established that secondary alcohols are oxidized by iodane 2 faster than primary alcohols. Our calculations corroborate this claim by showing that the overall activation energy for oxidation of 2-propanol (Figure 9) is ~2 kcal/mol lower in energy than that of 1-propanol. This consistency between theory and experiment lends further support to the validity of the α-hydride elimination mechanism. A plausible explanation for higher reactivity of secondary alcohols is as follows: in the transition structure of the α-hydride elimination, an electron deficiency is being developed at the Cα atom; this deficiency is alleviated if the Cα atom is more substituted. NO2

NO2

F3B O

I

H 36 -5.9

O O

H

I

O

O O

BF3 TS 36 15.0

Figure 9. Calculated important stationary points for 2-propanol oxidation via our proposed mechanism for α-hydride elimination. The relative free energies are given in kcal/mol.

Conclusion DFT calculations at the SMD/M06-2X/def2-TZVP//SMD/M06-2X/LANL2DZ,6-31G(d) level of theory were exploited to provide mechanistic insight into alcohol oxidation by an iodane catalyzed 20 ACS Paragon Plus Environment

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by BF3. Two main processes (ligand exchange and redox) were found to conduct the alcohol oxidation, both of which are accelerated by the involvement of BF3. The findings achieved in the course of this study may be summarized as follows: (i)

In contrast to previous reports, which have shown that addition of Brønsted/Lewis acid to iodane activates it toward a specific reaction, we found in this study that the ligand exchange between an iodane and alcohol is best facilitated if BF3 coordinates to the alcohol substrate and not iodane.

(ii)

Although the redox step of alcohol oxidation by an iodine(V) compound (IBX) proceeds via the conventional mechanism (alkoxy Cα deprotonation), the same mechanism does not apply to an iodine(III) reagent for alcohol oxidation.

(iii)

Once the ligand exchange process forms the alkoxy iodine(III) intermediate, the BF3 coordination to the alkoxy makes it prone to α-hydride elimination to give a BF3 stabilized ketone/aldehyde product and iodane [ArI(OAc)(H)]. The ensuing iodane is highly reactive toward reductive elimination to yield ArI + HOAc.

(iv)

In agreement with the kinetic isotope effect reported experimentally,61 the alkoxy αhydride elimination was found to be the rate determining step for the alcohol oxidation process.

(v)

Consistent with experimental observations, the α-hydride elimination mechanism predicts that the oxidation of secondary alcohols is more accessible energetically than that of primary alcohols.

Computational details


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Gaussian 0962 was used to fully optimize all the structures reported in this paper at the M06-2X level of theory.63-65 For all the calculations, solvent effects were considered using the SMD solvation model with 1-propanol as the solvent except for the calculated energy profile shown in Figure 9 for which 2-propanol is used as the solvent.66 The effective core potential of Hay and Wadt with a double-ξ valence basis set (LANL2DZ) was chosen to describe iodine.67, 68 The [631G(d)] basis set was used for other atoms.69 A polarization function was also added for I(ξd = 0.289).70 This basis set combination will be referred to as BS1. Frequency calculations were carried out at the same level of theory as those for the structural optimization. Transition structures were located using the Berny algorithm. Intrinsic reaction coordinate (IRC) calculations were used to confirm the connectivity between transition structures and minima.71, 72 To further refine the energies obtained from the SMD/M06-2X/LANL2DZ,6-31G(d) calculations, we carried out single-point energy calculations using the M06-2X functional method for all of the structures with a larger basis set (BS2). BS2 utilizes the def2-TZVP basis set73 on all atoms. Tight convergence criterion and ultrafine integral grid were also employed to increase the accuracy of the calculations. The free energy barriers for ligand dissociation/association via TSa, TSb, TSc, TSd, and TSe were estimated according to the protocol presented by Hall and Hartwig. In this protocol, for example, the Gibbs free energy barrier for a dissociation reaction such as A-B  A + B is estimated as ∆G‡ ≈ ∆H = HA + HB - HA-B. In this work, the free energy for each species in solution was calculated using the following formula: G = E(BS2) + G(BS1) - E(BS1) + ∆G1atm→1M (1) 22 ACS Paragon Plus Environment

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ACS Catalysis

where ∆G1atm→1M = 1.89 kcal/mol is the free-energy change for compression of 1 mol of an ideal gas from 1 atm to the 1 M solution phase standard state. An additional correction to Gibbs free energies was made to consider solvent (alcohol) concentration where a (alcohol)n, is directly involved in transformations. In such a case, the free energy of (alcohol)n is described as follows: G(alcohol)n = E(BS2) + G(BS1) - E(BS1) + ∆G1atm→1M + RTln([alcohol]/n)

(2)

where the last term corresponds to the free energy required to change the standard state of solvent from [alcohol]/n M to 1M.74, 75 These numerical correction values for monomeric and dimeric form of 1-propanol are 1.7 and 1.3 kcal/mol, respectively, and for monomeric form of 2propanol is 1.5 kcal/mol.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Figures S1−S2 and Cartesian coordinates of all calculated species (PDF)

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. ORCID Kaveh Farshadfar: 0000-0002-0863-1136 Brian F. Yates: 0000-0001-9663-3301 Alireza Ariafard: 0000-0003-2383-6380 23 ACS Paragon Plus Environment

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Page 24 of 32

Notes The authors declare no competing financial interest. Acknowledgements We thank the Australian Research Council (ARC) for project funding (DP18000904) and the Australian National Computational Infrastructure and the University of Tasmania for the generous allocation of computing time.

References 1.

Yoshimura, A.; Zhdankin, V. V., Advances in Synthetic Applications of Hypervalent

Iodine Compounds. Chem. Rev. 2016, 116, 3328-3435. 2.

Charpentier, J.; Fruh, N.; Togni, A., Electrophilic Trifluoromethylation by Use of

Hypervalent Iodine Reagents. Chem. Rev. 2014, 115, 650-682. 3.

Mejía, E.; Togni, A., Rhenium-Catalyzed Trifluoromethylation of Arenes and

Heteroarenes by Hypervalent Iodine Reagents. ACS Catal. 2012, 2, 521-527. 4.

Manna, S.; Serebrennikova, P. O.; Utepova, I. A.; Antonchick, A. P.; Chupakhin,

O. N., Hypervalent Iodine(III) in Direct Oxidative Amination of Arenes with Heteroaromatic Amines. Org. Lett. 2015, 17, 4588-4591. 5.

Souto, J. A.;

Zian, D.; Muñiz, K., Iodine(III)-Mediated Intermolecular Allylic

Amination under Metal-Free Conditions. J. Am. Chem. Soc. 2012, 134, 7242-7245. 6.

Wang, L.; Li, H.; Wang, L., Iron-Catalyzed C(sp3)–H Acyloxylation of Aryl-2H

Azirines with Hypervalent Iodine(III) Reagents. Org. Lett. 2018, 20, 1663-1666. 7.

Mendelsohn, B. A.; Lee, S.; Kim, S.; Teyssier, F.; Aulakh, V. S.; Ciufolini, M. A.,

Oxidation of Oximes to Nitrile Oxides with Hypervalent Iodine Reagents. Org. Lett. 2009,

11, 1539-1542.


Page 25 of 32 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

ACS Catalysis

8.

Zhdankin, V. V., Hypervalent Iodine (III) Reagents in Organic Synthesis.

ARKIVOC: Online Journal of Organic Chemistry 2009. 9.

Dohi, T.; Kita, Y., Oxidative C-C Bond Formation (Couplings, Cyclizations,

Cyclopropanation, etc.). PATAI'S Chemistry of Functional Groups, 1-84. 10.

Egalahewa, S.;

Albayer, M.;

Aprile, A.; Dutton, J. L., Diverse Reactions of

Thiophenes, Selenophenes, and Tellurophenes with Strongly Oxidizing I(III) PhI(L)2 Reagents. Inorganic Chemistry 2017, 56, 1282-1288. 11.

Tohma, H.; Kita, Y., Hypervalent Iodine Reagents for the Oxidation of Alcohols and

Their Application to Complex Molecule Synthesis. Adv. Synth. & Catal. 2004, 346, 111124. 12.

Merritt, E. A.; Olofsson, B., Diaryliodonium Salts: A journey from Obscurity to

Fame. Angew. Chem. Int. Ed. 2009, 48, 9052-9070. 13.

Wirth, T.; Hirt, U. H., Hypervalent Iodine Compounds: Recent Advances in

Synthetic Applications. Synthesis 1999, 1999, 1271-1287. 14.

Hari, D. P.;

Caramenti, P.; Waser, J., Cyclic Hypervalent Iodine Reagents:

Enabling Tools for Bond Disconnection via Reactivity Umpolung. Acc. Chem. Res. 2018,

51, 3212-3225. 15.

S Yusubov, M.; V Zhdankin, V., Hypervalent Iodine Reagents and Green

Chemistry. Curr. Org. Chem. 2012, 9, 247-272. 16.

Murphy, G. K.; Racicot, L.; Carle, M. S., The Chemistry between Hypervalent

Iodine (III) Reagents and Organophosphorus Compounds. Asian J. Org. Chem. 2018, 7, 837-851. 17.

Wirth, T., Hypervalent Iodine Chemistry in Synthesis: Scope and New Directions.

Angew. Chem. Int. Ed. 2005, 44, 3656-3665. 18.

Li, Y.; Hari, D. P.; Vita, M. V.; Waser, J., Cyclic Hypervalent Iodine Reagents for

Atom‐Transfer Reactions: Beyond Trifluoromethylation. Angew. Chem. Int. Ed. 2016, 55, 4436-4454. 19.

Zhong, W.; Yang, J.; Meng, X.; Li, Z., BF3.OEt2-Promoted Diastereoselective

Diacetoxylation of Alkenes by PhI(OAc)2. J. Org. Chem. 2011, 76, 9997-10004.


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

20.

Page 26 of 32

Dohi, T.; Morimoto, K.; Takenaga, N.; Goto, A.; Maruyama, A.; Kiyono, Y.;

Tohma, H.; Kita, Y., Direct Cyanation of Heteroaromatic Compounds Mediated by Hypervalent Iodine (III) Reagents: In Situ Generation of PhI(III)−CN Species and Their Cyano Transfer. J. Org. Chem. 2007, 72, 109-116. 21.

Takesue, T.; Fujita, M.; Sugimura, T.; Akutsu, H., A Series of Two Oxidation

Reactions of ortho-Alkenylbenzamide with Hypervalent Iodine(III): A Concise Entry into (3R,4R)-4-Hydroxymellein and (3R,4R)-4-Hydroxy-6-methoxymellein. Org. Lett. 2014,

16, 4634-4637. 22.

Wu, Y.;

Bouvet, S.;

Izquierdo, S.; Shafir, A., Synthesis of Polysubstituted

Iodoarenes Enabled by Iterative Iodine‐Directed para and ortho C-H Functionalization.

Angew. Chem. Int. Ed. 2019, 58, 2617-2621. 23.

Zhao, Z.;

Britt, L. H.; Murphy, G. K., Oxidative, Iodoarene‐Catalyzed

Intramolecular Alkene Arylation for the Synthesis of Polycyclic Aromatic Hydrocarbons.

Chem.: Eur. J. 2018, 24, 17002-17005. 24.

Tohma, H.; Iwata, M.; Maegawa, T.; Kiyono, Y.; Maruyama, A.; Kita, Y., A novel

and Direct Synthesis of Alkylated 2,2′-bithiophene Derivatives Using a Combination of Hypervalent iodine(III) reagent and BF3·Et2O. Org. Biomol. Chem. 2003, 1, 1647-1649. 25.

Narayan, R.; Matcha, K.; Antonchick, A. P., Metal‐Free Oxidative C-C Bond

Formation through C-H Bond Functionalization. Chem.: Eur. J. 2015, 21, 14678-14693. 26.

Liu, H.; Wang, X.; Gu, Y., Direct Acetoxylation and Etherification of Anilides Using

Phenyliodine bis (Trifluoroacetate). Org. Biomol. Chem. 2011, 9, 1614-1620. 27.

Ochiai, M.; Hirobe, M.; Yoshimura, A.; Nishi, Y.; Miyamoto, K.; Shiro, M., Internal

Delivery of Soft Chlorine and Bromine Atoms: Stereoselective Synthesis of (E)-βHalogenovinyl (aryl)-λ3-iodanes through Domino λ3-Iodanation-1, 4-Halogen ShiftFluorination of Alkynes. Org. Lett. 2007, 9, 3335-3338. 28.

Gu, Y.; Xue, K., Direct Oxidative Cyclization of 3-arylpropionic Acids Using PIFA

or Oxone: Synthesis of 3,4-dihydrocoumarins. Tetrahedron Lett. 2010, 51, 192-196. 29.

Dohi, T.; Ito, M.; Morimoto, K.; Iwata, M.; Kita, Y., Oxidative Cross‐Coupling of

Arenes Induced by Single‐Electron Transfer Leading to Biaryls by Use of Organoiodine(III) Oxidants. Angew. Chem. Int. Ed. 2008, 47, 1301-1304. 26 ACS Paragon Plus Environment

Page 27 of 32 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

ACS Catalysis

30.

Izquierdo, S.; Bouvet, S.; Wu, Y.; Molina, S.; Shafir, A., The Coming of Age in

Iodane‐Guided ortho‐C− H Propargylation: From Insight to Synthetic Potential. Chem.:

Eur. J. 2018, 24, 15517-15521. 31.

Zhang, H.;

Benzimidazolones

Huang, D.; via

Wang, K.-H.;

One-pot

Reaction

Li, J.; of

Su, Y.; Hu, Y., Synthesis of

Hydroxylamines,

Aldehydes,

and

Trimethylsilyl Cyanide Promoted by Diacetoxyiodobenzene. J. Org. Chem. 2017, 82, 1600-1609. 32.

Ochiai, M.; Yoshimura, A.; Mori, T.; Nishi, Y.; Hirobe, M., Difluoro-λ3-Bromane-

Induced Oxidative Carbon− Carbon Bond-Forming Reactions: Ethanol as an Electrophilic Partner and Alkynes as Nucleophiles. J. Am. Chem. Soc. 2008, 130, 3742-3743. 33.

Shimogaki, M.; Fujita, M.; Sugimura, T., Enantioselective C–C Bond Formation

during the Oxidation of 5-Phenylpent-2-enyl Carboxylates with Hypervalent Iodine(III). J.

Org. Chem. 2017, 82, 11836-11840. 34.

Shimogaki, M.; Fujita, M.; Sugimura, T., Metal-Free Enantioselective Oxidative

Arylation of Alkenes: Hypervalent-Iodine-Promoted Oxidative C−C Bond Formation.

Angew. Chem. Int. Ed. 2016, 55, 15797-15801. 35.

Liang, H.; Ciufolini, M. A., Chiral Hypervalent Iodine Reagents in Asymmetric

Reactions. Angew. Chem. Int. Ed. 2011, 50, 11849-11851. 36.

Kida, M.;

Sueda, T.;

Goto, S.;

Okuyama, T.; Ochiai, M., Synthesis and

Nucleophilic Substitution of Allenyl (m-nitrophenyl) Iodanes as a New Propynyl CationEquivalent Species: Synthesis of Propynyl Ethers, Esters, and Amides. Chem. Commun. 1996, 1933-1934. 37.

Uyanik, M.; Ishihara, K., Hypervalent Iodine-Mediated Oxidation of Alcohols.

Chem. Commun. 2009, 2086-2099. 38.

Izquierdo, S.; Essafi, S. p.; del Rosal, I.; Vidossich, P.; Pleixats, R.; Vallribera,

A.; Ujaque, G.; Lledós, A.; Shafir, A., Acid Activation in Phenyliodine Dicarboxylates: Direct Observation, Structures, and Implications. J. Am. Chem. Soc. 2016, 138, 1274712750. 39.

Su, J. T.; Goddard, W. A., Enhancing 2-Iodoxybenzoic Acid Reactivity by

Exploiting a Hypervalent Twist. J. Am. Chem. Soc. 2005, 127, 14146-14147. 27 ACS Paragon Plus Environment

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

40.

Page 28 of 32

Jiang, H.; Sun, T.-Y.; Wang, X.; Xie, Y.; Zhang, X.; Wu, Y.-D.; Schaefer, H. F.,

A Twist of the Twist Mechanism, 2-Iodoxybenzoic Acid (IBX)-Mediated Oxidation of Alcohol Revisited: Theory and Experiment. Org. Lett. 2017, 19, 6502-6505. 41.

Ganji, B.; Ariafard, A., DFT Mechanistic Investigation into Phenol Dearomatization

Mediated by an Iodine(III) Reagent. Org. Biomol. Chem. 2019, 17, 3521-3528. 42. Our calculations demonstrated that free energy change for transformation HOAc  ½(HOAc)2 is only 0.04 kcal/mol, suggesting that the monomeric and dimeric forms are likely in equilibrium. Therefore, it doesn’t make any difference which form of acetic acid is used in the DFT calculations. 43.

Hartwig, J. F.; Cook, K. S.; Hapke, M.; Incarvito, C. D.; Fan, Y.; Webster, C. E.;

Hall, M. B., Rhodium Boryl Complexes in the Catalytic, Terminal Functionalization of Alkanes. J. Am. Chem. Soc. 2005, 127, 2538-2552. 44.

Our calculations demonstrated that [OAc]- dissociation from 2 is endergonic by

23.7 kcal/mol with ∆G‡ = 34.2 kcal/mol and [F3B.OAc]- dissociation from 21 is endergonic by 9.2 with ∆G‡ = 18.3 kcal/mol (the dissociation activation free energies are computed based on Hall and Hartwig’s protocol). These results suggest that for 2 and 21 to undergo isomerization, they should preferentially proceed via concerted pathway (i.e. via transition structures TS2-15 and TS21-25, respectively) and not dissociation pathway. 45.

Following the suggestion of a reviewer, we also investigated the ligand exchange

between PrOH.BF3 (20) and iodane.BF3 (21) and found that this pathway is less likely to occur due to the fact that its transition structure (TS27-24) lies 2.8 kcal/mol higher in energy than TS22-23 (for details see Figure S1). 46.

Shu, S.; Li, Y.; Jiang, J.; Ke, Z.; Liu, Y., Mechanism of Hypervalent Iodine

Promoted Fluorocyclization of Unsaturated Alcohols: Metathesis via Double Acids Activation. J. Org. Chem. 2018, 84, 458-462. 47.

Zhang, J.; Szabó, K. l. n. J.; Himo, F., Metathesis Mechanism of Zinc-Catalyzed

Fluorination of Alkenes with Hypervalent Fluoroiodine. ACS Catal. 2017, 7, 1093-1100. 48.

Zhou, B.; Yan, T.; Xue, X.-S.; Cheng, J.-P., Mechanism of Silver-Mediated

Geminal Difluorination of Styrenes with a Fluoroiodane Reagent: Insights into Lewis-AcidActivation Model. Org. Lett. 2016, 18, 6128-6131.


Page 29 of 32 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

ACS Catalysis

49.

Lauriers, J.-D.; Legault, C., Metathetical Redox Reaction of (Diacetoxyiodo)

Arenes and Iodoarenes. Molecules 2015, 20, 22635-22644. 50.

Zhou, B.; Haj, M. K.; Jacobsen, E. N.; Houk, K. N.; Xue, X.-S., Mechanism and

Origins of Chemo-and Stereoselectivities of Aryl Iodide-Catalyzed Asymmetric Difluorinations of β-Substituted Styrenes. J. Am. Chem. Soc. 2018, 140, 15206-15218. 51.

Ling, L.; Liu, K.; Li, X.; Li, Y., General Reaction Mode of Hypervalent Iodine

Trifluoromethylation Reagent: A Density Functional Theory Study. ACS Catal. 2015, 5, 2458-2468. 52.

Dohi, T.; Kita, Y., Hypervalent Iodine Reagents as a New Entrance to

Organocatalysts. Chem. Commun. 2009, 16, 2073-2085. 53. Another alternative for the Cα deprotonation is the alcohol-assisted proton transfer to acetate starting from 24′. Although we are unable to locate a transition structure for this process, the energy scan calculations indicate that this possibility is unlikely to take place evidenced by the fact that it is very energy consuming with ∆E‡ > 50 kcal/mol (Figure S2). 54. Although in the reaction conditions mentioned in ref 36, an equivalent amount of BF3.Et2O to that of iodane was used, BF3 still acts as a catalyst (not a promoter) for the alcohol oxidation process. The reaction PrOH + propanal.BF3  PrOH.BF3 + propanal is calculated to be exergonic by -4.3 kcal/mol and occurs with ∆G‡ = 13.4 kcal/mol. This result supports the facile regeneration of the active catalyst (PrOH.BF3) and confirms that BF3 is not consumed during the reaction. 55.

Zhu, C.; Liang, Y.; Hong, X.; Sun, H.; Sun, W.-Y.; Houk, K.; Shi, Z., Iodoarene-

Catalyzed Stereospecific Intramolecular sp3 C–H Amination: Reaction Development and Mechanistic Insights. J. Am. Chem. Soc. 2015, 137, 7564-7567.55. 56. Funes‐Ardoiz, I.; Sameera, W.; Romero, R. M.; Martínez, C.; Souto, J. A.; Sampedro, D.;

Muñiz, K.; Maseras, F., DFT Rationalization of the Diverse Outcomes of the

Iodine(III)‐Mediated Oxidative Amination of Alkenes. Chem.: Eur. J. 2016, 22, 7545-7553. 57.

Sreenithya, A.; Surya, K.; Sunoj, R. B., Hypercoordinate iodine(III) Promoted

Reactions and catalysis: An Update on Current Mechanistic Understanding. Wiley

Interdisciplinary Reviews: Computational Molecular Science 2017, 7, e1299. 58.

Sreenithya, A.; Sunoj, R. B., Mechanistic Insights on Iodine(III) Promoted Metal-

Free Dual C-H Activation Involved in the Formation of a Spirocyclic bis-Oxindole. Org.

Lett. 2014, 16, 6224-6227. 59.

Beaulieu, S.; Legault, C. Y., Mechanistic Insights on the Iodine(III)-Mediated α-

Oxidation of Ketones. Chem.: Eur. J. 2015, 21, 11206-11211. 29 ACS Paragon Plus Environment

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

60.

Wodrich, M. D.;

Page 30 of 32

Caramenti, P.; Waser, J., Alkynylation of Thiols with

Ethynylbenziodoxolone (EBX) Reagents: α- or β- π-Addition? Org. Lett. 2016, 18, 60-63. 61. The KIE of 4.12 is achieved by DFT calculations which is somewhat comparable with the experimental value (4.84), as reported in ref 36. 62.

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.; Peralta, Jr., 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, 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, 2009. 63.

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 M06class Functionals and 12 Other Functionals. Theor. Chem. Acc. 2008, 120, 215-241. 64.

Zhao, Y.; Truhlar, D. G., Density Functionals with Broad Applicability in Chemistry.

Acc. Chem. Res 2008, 41, 157-167. 65.

Jiang, H.; Sun, T.-Y.; Wang, X.; Xie, Y.; Zhang, X.; Wu, Y.-D.; Schaefer III, H.

F., A Twist of the Twist Mechanism, 2-Iodoxybenzoic Acid (IBX)-Mediated Oxidation of Alcohol Revisited: Theory and Experiment. Org. Lett. 2017, 19, 6502-6505. 66.

Marenich, A. V.; Cramer, C. J.; Truhlar, D. G., Universal Solvation Model Based

on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J. Phys. Chem. B 2009, 113, 63786396. 30 ACS Paragon Plus Environment

Page 31 of 32 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

ACS Catalysis

67.

Hay, P. J.; Wadt, W. R., Ab Initio Effective Core Potentials for Molecular

Calculations. Potentials for the Transition Metal Atoms Sc to Hg.

J.

Chem.

Phys.

1985, 82, 270-283. 68.

Wadt, W. R.; Hay, P. J., Ab initio Effective Core Potentials for Molecular

Calculations. Potentials for Main Group Elements Na to Bi. J. Chem. Phys. 1985, 82, 284298. 69.

Hariharan, P. C.; Pople, J. A., The Influence of Polarization Functions on Molecular

Orbital Hydrogenation Energies. Theor. Chem. Acta. 1973, 28, 213-222. 70.

Höllwarth, A.; Böhme, M.; Dapprich, S.; Ehlers, A.; Gobbi, A.; Jonas, V.; Köhler,

K.; Stegmann, R.; Veldkamp, A.; Frenking, G., A Set of d-Polarization Functions for Pseudo-Potential Basis Sets of the Main Group Elements Al-Bi and f-Type Polarization Functions for Zn, Cd, Hg. Chem. Phys. Lett. 1993, 208, 237-240. 71.

Fukui, K., The Path of Chemical Reactions-the IRC Approach. Acc. Chem. Res

1981, 14, 363-368. 72.

Fukui, K., Formulation of the Reaction Coordinate. J. Chem. Phys. 1970, 74, 4161-

4163. 73.

Weigend, F.; Furche, F.; Ahlrichs, R., Gaussian Basis Sets of Quadruple Zeta

Valence Quality for Atoms H–Kr. J. Chem. Phys. 2003, 119, 12753-12762. 74.

Bryantsev, V. S.; Diallo, M. S.; Goddard Iii, W. A., Calculation of Solvation Free

Energies of Charged Solutes Using Mixed Cluster/Continuum Models. J. Phys. Chem. B 2008, 112, 9709-9719. 75.

Keith, J. A.; Carter, E. A., Quantum Chemical Benchmarking, Validation, and

Prediction of Acidity Constants for Substituted Pyridinium Ions and Pyridinyl Radicals. J.

Chem. Theory Comput. 2012, 8, 3187-3206.


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DFT Mechanistic investigation into BF3-catalyzed alcohol oxidation by

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