Chemoselective oxidation of unsaturated organosulfur, selenium and phosphorus compounds by molybdenum oxodiperoxo complexes: A computational investigation

Accepted Manuscript Research paper Chemoselective oxidation of unsaturated organosulfur, delenium and phosphorus compounds by molybdenum oxodiperoxo complexes: A computational investigation Lucelma P. de Carvalho, Kayo F. Silva, Leonardo L. dos Santos, Marcus V.P. dos Santos, Juliana A.B. da Silva, Ricardo L. Longo PII: DOI: Reference:

S0020-1693(17)30984-2 http://dx.doi.org/10.1016/j.ica.2017.08.021 ICA 17815

To appear in:

Inorganica Chimica Acta

Received Date: Revised Date: Accepted Date:

30 June 2017 10 August 2017 11 August 2017

Please cite this article as: L.P. de Carvalho, K.F. Silva, L.L. dos Santos, M.V.P. dos Santos, J.A.B. da Silva, R.L. Longo, Chemoselective oxidation of unsaturated organosulfur, delenium and phosphorus compounds by molybdenum oxodiperoxo complexes: A computational investigation, Inorganica Chimica Acta (2017), doi: http:// dx.doi.org/10.1016/j.ica.2017.08.021

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Chemoselective oxidation of unsaturated organosulfur, delenium and phosphorus compounds by molybdenum oxodiperoxo complexes: A computational investigation

Lucelma P. de Carvalhoa, Kayo F. Silvaa, Leonardo L. dos Santosa,b, Marcus V. P. dos Santosa, Juliana A. B. da Silvaa,b,*, Ricardo L. Longoc

a

Núcleo Interdisciplinar de Ciências Exatas e da Natureza, CAA, Universidade Federal de

Pernambuco, Nova Caruaru, 55.014-900, Caruaru, PE, Brazil b

Programa de Pós-Graduação em Química, Universidade Federal Rural de Pernambuco, 52171-

900, Recife, PE, Brazil c

Departamento de Química Fundamental, Universidade Federal de Pernambuco, 50740-540,

Recife, PE, Brazil.

* Corresponding author at: Núcleo Interdisciplinar de Ciências Exatas e da Natureza, CAA, Universidade Federal de Pernambuco, Nova Caruaru, 55.014-900, Caruaru, PE, Brazil E-mail address: [email protected] and [email protected].

Abstract Oxidation is fundamental for many chemical processes and the search for chemoselective oxidants is relevant because most substrates have different functional groups. For unsaturated organo-heteroatom (E) substrates R1E(CH2)nCH=CR2H, the olefin and/or the heteroatom can be

1

oxidized. It is known that molybdenum oxodiperoxo [MoO(O2)2L] complexes can selectively oxidize sulfide groups in the presence of alkenes. Thus, the effects of the substituents (R1 and R2) and of the separation n between the functional groups on the chemoselectivity were investigated by methods based on the density functional theory (DFT) for sulfides (E = S). The chemoselectivity was quantified by the difference between the Gibbs activation energies of the double bond (TS@C=C) and of the heteroatom (TS@E) oxidation pathways, ∆∆‡G = ∆‡G(TS@C=C) – ∆‡G(TS@E). Consistent with experimental observations, this oxidation is chemoselective towards the heteroatom (E = S, Se, and PCH3) for any unsaturated substrate or ancillary ligand L in the complex. For unsaturated organosulfur compounds, it is shown that an increase in the electronegativity of R1 leads to a decrease of the chemoselectivity, which can be correlated with the atomic charge at the sulfur center. The separation n affects the chemoselectivity similarly to the electronegativity of R1, namely, differences between sp2 and sp3 carbon centers. The ancillary ligand L = OPH3, pyrazole, pyridine N-oxide, and Si(OH)4, affects the reactivity of the complex and its chemoselectivity, where L = Si(OH)4 shows the highest reactivity and the least selectivity; however, ∆∆‡G is still large enough (4.3 kcal/mol) to provide high chemoselectivity. This agrees with the experimental observations related to the oxidations by [MoO(O2)2L] complexes supported on silica. These quantitative results and the qualitative trends and correlations can be helpful in the design of more efficient and greener Mo-based oxidants.

Keywords: Molybdenum complexes Oxidation reactions

2

Chemoselectivity Density functional calculations.

1. Introduction Oxidation reactions are one of the most important in organic synthesis and one of the most difficult to adhere to the green chemistry principles [1]. Thus, the development of efficient oxygen transfer reagents that avoid over-oxidation and that are chemoselective is a relevant goal. Usually, transition metal complexes, especially those with peroxide ligands, are employed in these reactions, because they are versatile and can be regenerated after the reaction [1]. In particular, molybdenum complexes can be selective in the oxidation of several organic substrates [2-15]. Some examples include epoxidation of alkenes, oxyketonation, oxidation of sulfur-, nitrogen-, phosphorus- and selenium-organo compounds [16-18], mainly when combined with a mild oxidant [5, 15]. Since the introduction of oxo-diperoxo-type transition metal complexes by Mimoun [19] for the epoxidation of olefins, the use of molybdenum oxo-(di)peroxo based complexes as selective oxidation reagents has become important because of its impact on synthesis and industry. As a result, many molybdenum complexes have been designed, synthesized and applied in oxidation reactions [5,15,20-25], because their reactivity can be controlled by modulating their electronic and structural properties through the ligands, the metal, and the medium [5, 26, 27], making them more suitable to develop sustainable strategies and protocols as well as greener oxidants. In fact, they are replacing older procedures by solving or minimizing several problems such as, low activity, poor yield, low selectivity, harsh conditions and difficulties to handle, and laborious purification processes due to the generation of by
products.

3

The scope of molybdenum oxo-(di)peroxo complexes has been widen, for instance, by their use in the oxidation of sulfides to sulfoxides and/or sulfones [5, 16, 20-23, 28-36], which are important intermediates in organic synthesis, especially, of bioactive compounds and as chiral auxiliaries in enantiomeric processes. Sulfoxides are also important in the pharmaceutical industry as they are found in numerous drugs, such as anti-ulcer (proton pump inhibitor), antimicrobial, antidepressants, antiallergics, antihypertensive, cardiotonic agents, vasodilators, amongst other [32, 33, 37]. Thus, many procedures were developed for oxidation of sulfides, however, just a few are selective toward the sulfoxides and most lead to over-oxidation yielding the corresponding sulfone [36, 38, 39]. In this context, molybdenum oxo-(di)peroxo complexes can be quite selective because the oxidation of sulfides yields practically only sulfoxides [12, 2024, 28, 37, 40]. For example, it has been shown that the molybdenum oxo-diperoxo complexes, [MoO(O2)2L1L2], where L1 = pyrazole or pyridine N-oxide, L2 = H2O or silica (adsorbed onto silica gel), are highly selective yielding only sulfoxide products in the oxidation reactions of unsaturated sulfides [18]. This result also show that these complexes are highly chemoselective because they can oxidize the sulfide moiety in the presence of unsaturation. In addition, there are some recent examples of highly stereoselective synthesis of chiral sulfoxides obtained from the oxidation of achiral sulfides by oxo-(di)peroxo complexes [12, 16, 31-33 ,41, 42]. Designing new complexes with higher activity and selectivity in the oxidation of multifunctional organic substrates, and additionally that are easily recovered and regenerated, requires a detailed knowledge of the reaction mechanism and the effects of the ligands, metal and medium. In fact, this is still a challenging task despite the large number of studies related to oxidations, especially using oxo-(di)peroxo complexes. In this context, computational quantum chemical methods can be useful to establish the mechanism and to comprehend quantitatively the

4

behavior of complexes in oxygen transfer reactions [6, 12, 35, 36, 50]. Thus, we report a computational investigation of the oxidation of unsaturated substrates R1X(CH2)nCH=CHR2 by [MoO(O2)2L] complexes. In particular, the chemoselectivity of the [MoO(O2)2OPH3] complex in the oxidation of CH3ECH2CH=CH2, with E = S, Se and PCH3, was addressed, as well as the effects of the R1 and R2 groups and the size of the alkyl chain (n) in the R1S-(CH2)n-CH=CHR2 substrate, namely, R1 = methyl, mono-, di- and trifluoromethyl, ethyl, phenyl, R2 = H and CH3, and n = 0 and 1. The effects of the ligand L in the [MoO(O2)2L] complex on the chemoselective oxidation CH3SCH=CH3 were explored for L = phosphine oxide (OPH3), pyrazole, pyridine Noxide, and orthosilicic acid, Si(OH)4, to model the complex adsorbed in silica.

2. Methods and computational procedures All molecular structures were calculated without any symmetry constraints and were characterized by their force constants. All calculations were performed with Gaussian 09 program (Rev. D.01) [43] using the B3LYP functional [44] and the 6-311+G(2df,2p) basis sets [45] for all atoms, except for molybdenum that was described by the Def2-SVP effective core potential (ECP) and basis set [46]. The proper connection between the reactants and products by the transition state was verified by the intrinsic reaction coordinate (IRC). Activation quantities, such as energy, Gibbs free energy and entropy, were obtained as the difference between their values in the transition state (TS) and the separated reactants (substrate + [MoO(O2)2L] complex) at 298 K. The activation energies were calculated without the ZPE (zero-point vibrational energy) corrections. Because the chemoselectivity calculations may depend on the methodology, the effects of the ECP/basis set at the molybdenum on the oxidation of sulfur in the CH3SCH2CH=CH2

5

substrate by the [MoO(O2)2OPH3] complex were systematically investigated at the B3LYP/X/6311+G(2df,2p) level, where X = LanL2DZ, Def2-SVP, Def2-TZVP, Def2-QZVP, cc-pVDZ-PP, and cc- PVTZ-PP.

3. Results and discussion Before presenting the results of the effects of the substrate R1E(CH2)nCH=CR2H and of the ligand [MoO(O2)2L] on the oxidation chemoselectivity, some general remarks about the oxidation of unsaturated organosulfur substrates by oxo-diperoxo complexes and the reaction mechanisms will be addressed. In addition, the sulfide oxidation of CH3SCH2CH=CH2 by [MoO(O2)2OPH3] will be investigated to quantify the effects of the ECP and basis set on the molybdenum and to establish a quantitative methodology for the chemoselectivity.

3.1. General remarks and aspects of oxidation by oxo-diperoxo complexes The oxidation of unsaturated organosulfur substrates can generate an epoxide (oxidation of the unsaturation), a sulfoxide (oxidation of the sulfide), and a sulfone (oxidation of the sulfoxide or over-oxidation) [47]. Thus, it has a potential to produce a complex mixture with low yields of the product of interest and the development of chemoselective oxidants becomes relevant. Usually, oxo-diperoxo complexes are chemoselective in the oxidation of sulfides with respect to double bonds through a kinetic control [28]. Namely, the oxidation of sulfides by oxodiperoxo molybdenum complexes has lower barrier, although their products are less stable [12, 35, 36, 48]. The transition state theory (TST) has been quite successful in describing kinetically controlled reactions [49]. Its application requires the structures and vibrational frequencies of the transition states and reactants, which can be obtained adequately by quantum chemical

6

computational methods, especially those based in the density functional theory (DFT). If the factors affecting the stabilities of the transition states are determined and quantified, they can be promptly employed in the design and development of more efficient (active and selective) oxidants. The isolated MoO(O2)2 moiety in the oxo-diperoxo complexes has already asymmetric peroxide units with a Mo–O bond distance slightly longer than the other. Thus, the ancillary ligand L coordinates perpendicular to the Mo-oxo bond and between the distorted peroxide groups as can be observed in Fig. 1 for the [MoO(O2)2L] complexes. These calculated structures are in excellent agreement with the crystallographic [50] data and with other DFT calculations [35]. All structures of the stationary points in the reaction profiles calculated at the B3LYP/Def2SVP/6-311+G(2df,2p) level are presented in the Supplementary data.

Fig. 1. Molecular structures of the complexes [MoO(O2)2L] with L = phosphine oxide, OPH3 (a), pyrazole (b), pyridine N-oxide (c), and Si(OH)4 (d) obtained at B3LYP/Def2-SVP/6311+G(2df,2p) level. Selected distances in 10–10 m.

The oxidation reaction mechanism of the alkenes by oxo-diperoxo transition metal complexes has two proposed pathways: Mimoun and Sharpless, which has been extensively investigated by experimental and computational techniques [35,50]. The Sharpless mechanism

7

has become a consensus for oxidation of unsaturated substrates by Mo-(di)peroxo based complexes [12, 35, 36, 50, 48]. A Sharpless-type mechanism will also be assumed for the oxidation of sulfides according to computational and experimental results that suggest that this mechanism is more likely than a Thiel-type pathway [23, 51, 52]. In addition, the intrinsic structure of MoO(O2)2 as well as those of the complexes in Fig. 1 suggest that there should be a preferred oxygen transferred from the peroxo units, namely that with longer Mo–O distance, which has been observed by calculations and experiments and, therefore, only the peroxide oxygen trans to the ancillary ligand L will be considered in the transfer to the substrate [35,51,52]. A typical reaction energy profile of unsaturated organosulfur oxidation by [MoO(O2)2L] complexes is illustrated in Fig. 2 for the Sharpless-type mechanism, where the substrate does not coordinate to the metal center.

Fig. 2. Illustration of a typical reaction energy profile of the oxidation of unsaturated organosulfur substrates by [MoO(O2)2L] complexes via Sharpless-type mechanism. The reaction

8

[MoO(O2)2(OPH3)] + CH3SCH2CH2=CH2 through TS@C=C yields the oxidation of the double bond and the epoxide, 2-((methylthio)methyl)oxirane, product, while via TS@S leads to the oxidation of sulfur center and produces the sulfoxide, 3-(methylsulfinyl)prop-1-ene, product.

3.2. Description of the molybdenum atom in the chemoselectivity studies It has been shown that the B3LYP functional is adequate to describe the oxidation of alkenes by oxodiperoxide complexes, as long as appropriated basis sets are employed. Thus, a versatile and extended basis set, 6-311+G(2df,2p), was chosen to describe all atoms, except molybdenum that requires a special treatment due to the large number of electrons and the relativistic effects. For this atom, effective core potentials (ECPs) derived from relativistic calculations are usually employed, however, several ECPs are available for Mo [53] and a proper one needs to be selected to provide quantitative results. In fact, a benchmark study regarding the basis sets at the Mo atom to describe oxidation reactions is available employing the generator coordinate approach, which has suggested a very large basis [54]. Thus, the oxidation of the sulfide in the CH3SCH2CH=CH2 substrate by [MoO(O2)2OPH3] was selected to investigate the effects of the ECP/basis sets at the Mo atom on the activation energy, Gibbs free energy, and entropy. This systematic study was performed at the B3LYP/X/6-311+G(2df,2p) level, where X = LanL2DZ, Def2-SVP, Def2-TZVP, Def2-QZVP, cc-pVDZ-PP, and cc-PVTZ-PP is the ECP/basis set at Mo. The activation parameters are given in Table 1 and are in excellent agreement, namely, 19.0 kcal/mol, with a previous benchmark study [35], except for X = LanL2DZ. Because X = Def2-SVP presents the lowest computational demand and has provided converged results for these properties, it was chosen for the chemoselectivity investigations.

9

Table 1. Activation energy, ∆‡E, activation Gibbs energy, ∆‡G, and activation entropy, ∆‡S for the oxidation of the sulfide in CH3SCH2CH=CH2 (via TS@S) by the [MoO(O2)2OPH3] complex, calculated at the B3LYP/X/6-311+G(2df,2p) level relative to the separated reactants. Basis set and effective core potential (ECP) at Mo (X) TS2 – reagents

LanL2DZ Def2-SVP Def2-TZVP Def2-QZVP cc-pVDZ-PP cc-pVDTZ-PP

∆‡E (kcal/mol) ∆‡G (kcal/mol) ∆‡S (cal mol–1 K–1)

12.4

6.6

6.6

6.7

6.3

6.6

18.2

18.2

18.4

18.0

18.3

-37.7

-37.8

-38.1

-38.0

-38.0

It is worth mentioning the calculated ∆‡G for the oxidation of the double bond in CH3SCH2CH=CH2 (via TS@C=C) with the selected computational level, B3LYP/Def2-SVP/6311+G(2df,2p), was 26.2 kJ/mol, which is also in excellent agreement with a detailed benchmark study, namely, 26.4 kJ/mol [35]. The structures of the transition states calculated at this computational level for both pathways (TS@C=C and TS@S) are presented in Fig. 3 with some selected interatomic distances. These structures are in excellent agreement with previous ones calculated with a very large basis set at the Mo atom. This methodology was then applied to the investigations of the substrate (R1X(CH2)nCH=CR2H) and of the ancillary ligand ([MoO(O2)2L]) effects on the oxidation chemoselectivity.

10

Fig. 3. Molecular structures of the transition states obtained at the B3LYP/Def2-SVP/6311+G(2df,2p) level for the [MoO(O2)2OPH3] + CH3SCH2CH=CH2 reaction (a) via TS@C=C (oxidation of the double bond) and (b) via TS@S (sulfur oxidation). Selected distances in 10–10 m.

3.3. Chemoselective oxidation of R1E(CH2)nCH=CR2H (E = S, Se, and PCH3) by [MoO(O2)2OPH3] Experimental and computational studies have already shown the preference for oxidation of sulfur center in the presence of unsaturation by [MoO(O2)2L]. However, the effects of the substituents in both sulfur and olefin groups as well as the separation between these groups have not been systematically explored. In addition, the scope of this oxidation reaction to other heteroatoms has not yet been probed. Thus, we present an investigation of the oxidation by the [MoO(O2)2OPH3] complex of substrates with different substituents, alkyl chain and heteroatoms, namely, R1E(CH2)nCH=CR2H, with R1 = CH3, CH2CH3, phenyl, CH2 F, CHF2, and CF3, R2 = H and CH3, n = 0 and 1, E = S, Se, and PCH3. The calculated activation energy, ∆‡E, the Gibbs free activation energy, ∆‡G, and the activation entropy, ∆‡S, for these reactions are presented in Table 2 and in the Supplementary data.

11

The calculations predict a strong kinetic preference (ca. 5-11 kcal/mol) for the oxidation of the heteroatomic center (via TS@E) with respect to the oxidation of alkene group (via TS@C=C). A slight selectivity (ca. 1.5-3.0 kcal/mol) is predicted for the oxidation of phosphorous compared to selenium and sulfur, and of selenium relative to sulfur.

Table 2. Activation energy, ∆‡E (kcal/mol), activation Gibbs energy, ∆‡G (kcal/mol), and activation entropy, ∆‡S (cal mol–1 K–1) for the oxidation of the alkene (via TS@C=C) and of the heteroatom (via TS@E) in the R1E(CH2)nCH=CR2H substrate (E = S, Se, and PCH3) by the [MoO(O2)2OPH3] complex, calculated at the B3LYP/Def2-SVP/6-311+G(2df,2p) level relative to the separated reactants. The difference between the Gibbs activation energies, ∆∆‡G (kcal/mol), of the TS@C=C and TS@E pathways are also presented. All thermochemical properties were determined at 298 K and the values of ∆∆‡G (kcal/mol) were estimated at 198 and 398 K. Substrate

TS@C=C

‡

∆E

TS@X

‡

‡

∆G ∆S

‡

∆E

TS@C=C – TS@X

‡

∆∆‡G

∆∆‡G

∆∆‡G

(298 K)

(198 K)

(398 K)

‡

∆G ∆S

CH3SCH=CH2

12.8

24.9 -39.1

8.2

19.9 -38.2

5.0

4.7

4.9

CH3SCH2CH=CH2

14.0

26.2a) -39.2

6.6

18.2 b) -37.7

8.0

7.6

8.0

CH3CH2SCH2CH=CH2 14.2

26.3 -39.0

6.6

18.7 -39.4

7.6

7.5

7.4

CH3SCH2CH=CHCH3

13.2

26.5 -43.0

6.4

18.3 -38.7

8.2

7.7

8.6

(Phenyl)SCH2CH=CH2 14.5

26.4 -38.7

8.0

19.6 -37.8

6.8

6.6

6.8

CH2FSCH2CH=CH2

15.0

26.6 -37.7

8.2

20.2 -39.0

6.4

6.6

6.3

CHF2SCH2CH=CH2

15.6

27.4 -38.2

9.6

21.4 -38.1

6.0

6.0

6.0

12

CF3SCH2CH=CH2

15.6

27.7 -39.3

13.7

25.2 -37.1

2.5

2.2

2.7

CH3SeCH2CH=CH2

13.8

25.9 -39.1

5.0

16.4 -37.7

9.4

9.1

9.4

(CH3)2PCH2CH=CH2

14.5

26.0 -37.3

4.1

15.0 -35.6

11.0

10.7

11.0

P(CH3)3

-----

----- -----

4.4

15.2 -35.5

-----

-----

-----

a) ‡

∆ G = 26.4 kcal/mol [35]. b)∆‡G = 19.0 kcal/mol [35].

Because thermodynamics properties and kinetic parameters are dependent on the temperature, the selectivity, quantified by ∆∆‡G, could also be affected by the temperature. Thus, Table 2 presents the calculated values of ∆∆‡G at 198 K and 398 K (see Supplementary data), in addition to the room temperature values. Even with a variation of 100 K around 298 K, the temperature effects on the selectivity are insignificant (< 0.3 kcal/mol), which are expected because the differences of the entropies between the two reaction pathways (via TS1 and via TS2), ∆∆‡S, are very small. The size of the alkyl chain (R1) at the sulfite has practically no effect on the Gibbs activation energy. However, the nature of the R1 substituent affects quite strongly the activation free energy difference between the oxidation of the alkene and of the sulfide groups. In fact, as R1 becomes more electronegative, e.g. phenyl and CH(3 – j)Fj (j = 1-3), this difference decreases from ca. 8 to 2.5 kcal/mol mainly due to an increase of the activation energy of the sulfide oxidation pathway, whereas the oxidation of the unsaturation increases at most 1.5 kcal/mol. This suggests that the electron density difference between the sulfur and the alkene is the main factor for the chemoselective oxidation of unsaturated sulfides. Indeed, the Mulliken charges at the sulfur atom in the H(3 – j)FjCSCH2CH=CH2 substrates are −0.15, −0.10, −0.01, and +0.04e for j = 0 to 3, respectively, which thus correlate with the electronegativity of R1 as well as with the

13

calculated chemoselectivity (∆∆‡G) in Table 2. It is noteworthy that as the sulfur center becomes less nucleophilic with the increase of the electronegativity of R1, the transition state for the oxidation of the sulfide (TS@S) becomes later, that is, the O–S distance decreases, while the O– O distance increases as can be observed in Fig. 4. This is consistent with the Hammond principle [49] because the late transition states are more similar to the products, which increases the activation barriers for kinetically controlled reactions for the least stable product. Thus, the lateness of the transition state for the sulfide oxidation correlates with the decrease of the chemoselectivity (∆∆‡G).

Fig. 4. Molecular structures of the transition states for the sulfide oxidation (via TS@S) of H(3 – j) FjCSCH2-CH=CH2

substrates by the [MoO(O2)2OPH3] complex, with j = 0 (a), 1 (b), 2 (c) and

3 (d) obtained at the B3LYP/Def2-SVP/6-311+G(2df,2p) level. Selected distances in 10–10 m.

On the other hand, the energy difference between the molecular orbital (MO) associated to the π(C–C) bonding orbital and to the lone pair at the sulfur center has been suggested as a descriptor for the chemoselectivity [35]. This is consistent with the observed trends in Table 2, because as R1 becomes more electronegative the lone pair MO would become more stable and

14

the energy difference relative to the π(C–C) MO decreases, which causes a decrease of the chemoselectivity. This is corroborated by the energy difference between the π(C–C) MO and the highest lone pair MO at the sulfur in the H(3 – j)FjCSCH2-CH=CH2 substrates, namely, 1.2, 0.8, 0.7, and 0.5 eV for j = 0 to 3, respectively. The effects of the electronegativity of the groups bounded to the sulfur on the chemoselectivity can also explain the decrease of ∆∆‡G from 8.0 kcal/mol for CH3SCH2CH=CH2 to 5.0 kcal/mol for CH3SCH=CH2, because the sp2 carbon is more electronegative than a sp3 one [49].

3.4. Effects of the ancillary ligand L in [MoO(O2)2L] complexes on the chemoselective oxidation of CH3SCH=CH2 The [MoO(O2)2L] complex can become a greener oxidant by increasing its chemoselectivity (less by-products), by making the dioxoperoxide product [MoOO(O2)L] as reactive and selective as the parent complex [MoO(O2)2L], and by the easiness of regenerating the parent oxodiperoxide complex, so the transition metal can be recycled. In addition, to simplify the separation of the inorganic and organic components, the complex can be supported in a solid matrix such as silica. These features can be modulated by the ancillary ligand L, so the effects of L = phosphine oxide (OPH3), pyrazole, pyridine N-oxide, and orthosilicic acid, Si(OH)4, on the chemoselectivity of CH3SCH=CH2 were investigated. The ancillary ligand Si(OH)4 models the complex supported in silica. The transition state structures for the sulfur oxidation (via TS@S) are presented in Fig. 5 and for the oxidation of the double bond (via TS@C=C) are shown in Fig. 6, whereas the values of the activation properties for both pathways are presented in the Table 3. The largest

15

chemoselectivity (∆∆‡G) is obtained with the pyrazole ligand (5.3 kcal/mol) and the smallest with Si(OH)4 (4.3 kcal/mol), whereas the later ligand leads to the smallest Gibbs activation energy. This is consistent with the reactivity-selectivity principle, namely, as the reactivity increases (activation energy decreases) the selectivity decreases [49]. Comparing the transition state structures related to TS@S and TS@C=C for the complex with L = pyrazole (Figs. 5a and 6a), it can be observed that TS@S is less distorted than TS@C=C, which correlates with the smaller barrier of TS@S and the larger barrier of TS@C=C. A similar behavior is noticed for the complexes with L = OPH3, pyNO, and Si(OH)4. In addition, a strong correlation between the S–O distances and the activation barriers is observed, namely, as more distorted the complex becomes in the transition state, quantified by differences in the O–O and Mo–O(peroxo, trans) distances in the transition state relative to the isolated complex, the activation barrier becomes higher. In fact, these distortion effects on the transition metal complexes have already reported for a catalyst based on molybdenum or tungsten in a d0-olefin catalyzed metathesis [55]. These authors have used an energy partitioning scheme of the energy barrier calculated as a sum of the energies required to distort the catalyst and ethylene into the transition state structure and the interaction energy between the two fragments in the transition state. They have observed that at the transition state, the olefin and the metal are quite far apart (> 3 Å) and the C=C bond length is almost equal to that in the isolated ethylene, which gives a negligible distortion energy of the olefin and a small metal-olefin interaction. Thus, the activation energy barrier associated with the formation of this transition state is practically determined by the distortion energy of the metal complex moiety. It is noteworthy that the complex with L = Si(OH)4 is the most reactive for the sulfide oxidation, which agrees with the experimental observation that the [MoO(O2)(OPH3)] complex

16

adsorbed on silica gel oxidizes unsaturated sulfides to unsaturated sulfoxides exclusively. However, our results for this system shows a slight decrease of the chemoselectivity, in contradiction to a previous suggestion [28]. Despite the differences in the chemoselectivity associated with the ancillary ligand L (Table 3), the smallest ∆∆‡G (4.3 kcal/mol) is still large enough to maintain a very high selectivity towards the oxidation of sulfides.

Table 3. Activation energy, ∆‡E (kcal/mol), activation Gibbs energy, ∆‡G (kcal/mol), and activation entropy, ∆‡S (cal mol–1 K–1) for the oxidation of the double bond (TS@C=C) and of the sulfur (TS@S) in CH3SCH=CH2 by the [MoO(O2)2L] complex with different ancillary ligands L, calculated at the B3LYP/X/6-311+G(2df,2p) level relative to the separated reactants. Via TS@C=C

Via TS@S

TS@C=C – TS@S

Ligand L

∆‡E

∆‡G ∆‡S

∆‡E

∆ ‡G

∆‡S

∆∆‡G

Pyrazole

13.8

26.3 -40.3

9.1

21.0

-39.2

5.3

OPH3

12.8

24.9 -39.1

8.2

19.9

-38.2

5.0

Pyridine N-oxide

14.4

26.6 -39.4

10.2

21.9

-38.7

4.7

Si(OH)4

10.4

22.0 -37.4

6.2

17.7

-37.7

4.3

17

Fig. 5. Molecular structures of the transition states obtained at the B3LYP/Def2-SVP/6311+G(2df,2p) level for the sulfide oxidation in CH3SCH=CH2 (via TS@S) by the [MoO(O2)2L] complex, with (a) L = pyrazole, (b) L = OPH3, (c) L = pyridine N-oxide, and (d) L = Si(OH)4 (silica model). Selected distances in 10–10 m.

Fig. 6. Molecular structures of the transition states obtained at the B3LYP/Def2-SVP/6311+G(2df,2p) level for the double bond oxidation in CH3SCH=CH2 (via TS@C=C) by the [MoO(O2)2L] complex, with (a) L = pyrazole, (b) L = OPH3, (c) L = pyridine N-oxide, and (d) L = Si(OH)4 (silica model). Selected distances in 10–10 m.

4. Conclusion Quantum chemistry calculations at the B3LYP/Def2-SVP/6-311+G(2df,2p) level were successfully employed to quantify the chemoselectivity of the molybdenum oxodiperoxo [MoO(O2)2L] complexes in the oxidation of unsaturated heteroatom substrates R1E(CH2)nCH=CR2H (E = S, Se, and PCH3). The complex [MoO(O2)2OPH3] is highly selective towards the oxidation of the heteroatom compared to the oxidation of the double bond. This chemoselectivity increases from E = S to Se to PCH3. The electronegativity of the substituent at

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the heteroatom (R1) affects the chemoselectivity, namely, as its electronegativity increases the chemoselectivity decreases. The ancillary ligand L affects the reactivity of the [MoO(O2)2L] complex with L = Si(OH)4 (model of silica) being the most active complex and having the least chemoselectivity, which, however, is large enough to provide very high selectivity. These results can aid the development of more efficient and greener Mo-based oxidants and they have expanded the scope of the oxidations by [MoO(O2)2L] complexes to heteroatom other than sulfur.

Acknowledgements The Brazilian Agencies FACEPE, CNPq, CAPES and FINEP are acknowledged for providing partial financial support under grants PRONEX APQ-0675-1.06/14, APQ-0236-1.06/14 and APQ-1007-1.06/15, and the computer centers CESUP, CENAPAD-SP and CENAPAD-UFC for computational support. M.V.P.S. thanks FACEPE/CNPq for the DCR Fellowship under grant APQ-0102-1.06/14, R.L.L. thanks CNPq for the PQ-fellowship (Proc. no. 308823/2014-1), L.L.S. thanks FACEPE for graduate scholarship and L.P.C, K.F.S and M.M.S. for undergraduate scholarship.

Appendix A. Supplementary data Supplementary data containing the equations for the temperature effects, the Cartesian coordinates, the sum of the electronic and thermal free energies calculated for all reactants and transition states associated with this article can be found, in the online version, at http://dx.doi.org/_.

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HIGHLIGHTS • Chemoselectivity described by DFT. • Expanding the scope of chemoselective oxidation of heteroatom-unsaturated substrates. • Chemoselectivity is directed by the electronegativities in the substrate. • Ancillary ligand L affects reactivity and chemoselectivity of MoO(O2)2L complexes.

GRAPHICAL ABSTRACT

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