Experimental and Theoretical Studies on the Implications of Halide

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Experimental and Theoretical Studies on the Implications of Halide Dependent Aqueous Solvation of Sm(II) Alejandro Ramirez-Solis, Caroline Bartulovich, Tesia V. Chciuk, Jorge Hernández-Cobos, Humberto Saint-Martin, Laurent Maron, William R. Anderson, Anna M. Li, and Robert A Flowers J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b09857 • Publication Date (Web): 09 Nov 2018 Downloaded from http://pubs.acs.org on November 9, 2018

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Journal of the American Chemical Society

Experimental and Theoretical Studies on the Implications of Halide Dependent Aqueous Solvation of Sm(II) Alejandro Ramírez-Solísa*, Caroline O. Bartulovich,b Tesia V. Chciuk,b Jorge Hernández-Cobosc, Humberto Saint-Martinc, Laurent Marond, William R. Anderson Jr.b, Anna M. Li,b and Robert A. Flowers IIb* aDepto.

de Física, Centro de Investigación en Ciencias-IICBA Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209 México. bDepartment of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, United States cInstituto de Ciencias Físicas, UNAM. Cuernavaca, Morelos. 62210 México. dLaboratoire de Physique et Chimie de Nanoobjets, Université de Toulouse, INSA-CNRS-UPS, 135, Avenue de Rangueil, 31077 Toulouse, France. ABSTRACT: The addition of water to Sm(II) has been demonstrated to have a significant impact on the reduction of organic substrates, with the majority of research dedicated to the most widely-used reagent, samarium diiodide (SmI2). The work presented herein focuses on the reducing capabilities of samarium dibromide (SmBr2) and demonstrates how the modest change in halide ligand results in observable mechanistic differences between the SmBr2-water and the SmI2-water systems that have considerable implications in terms of reactivity between the two reagents. Quantum chemical results from Born-Oppenheimer molecular dynamics (BOMD) simulations show significant differences between SmI2-water and SmBr2-water with the latter displaying less dissociation of the halide that results in a lower coordination number for water. Experimental results are consistent with computational results and demonstrate that the coordination sphere of SmBr2 is saturated at lower concentrations of water. In addition, coordination-induced bond-weakening of the O-H bond is demonstrably different for water bound to SmBr2 leading to an estimated O-H bond-weakening of at least 83 kcal/mol, a bond-weakening nearly 10 kcal/mol larger than SmI2-H2O. Experimental results also demonstrate that the use of alcohols in place of water with SmBr2 leads to substrate reduction, albeit several orders of magnitude slower than SmBr2-water. The difference in rates resulting from the change in proton donor is attributed to a ratelimiting PCET in SmBr2-water, and a sequential ET-PT in SmBr2-alcohols systems where ET is rate-limiting.

Introduction Over the last 30 years a considerable volume of research has explored the reactivity and selectivity of samarium diiodide (SmI2), a widely-used and important reducing agent in synthetic organic chemistry.1–4 Various additives can be combined with SmI2 to effectively promote the reduction or reductive coupling of numerous functional groups such as esters, anhydrides, amides, carbonyls, and arenes.5–7 In particular, the presence of water has shown a significant effect on the reduction of substrates by SmI2. Procter and Szostak have demonstrated the utility of SmI2-water in reductions and reductive coupling reactions involving substrates typically recalcitrant to electron transfer (ET).8–13 Although the basis for the unusual reactivity of SmI2-water was proposed to be a consequence of a reversible first electron transfer then proton transfer (ET-PT) followed by a rate-limiting second ET, recent work in our group has demonstrated that many Sm(II)-induced reductions proceed through a rate-limiting proton-coupled electron-transfer (PCET).14–18 Coordination-induced bondweakening of water bound to Sm(II) provides a configuration uniquely suited for PCET, enabling the reduction of substrates that are too endergonic to proceed through electron transfer. This conclusion was supported by the recent studies of Mayer and Kolmar who demonstrated that even electron-rich enamines are readily reduced by SmI2-water, further supporting the likelihood of PCET from the reagent system.19

Aside from SmI2, other Sm(II) halides, including samarium dibromide (SmBr2) and samarium dichloride (SmCl2), have found applications in synthesis. Both reagents are readily prepared by the addition of several equivalents of lithium bromide or chloride salts to SmI2 in THF.20 Interestingly, the modest change of halide has a large impact on the reactivity and selectivity of Sm(II).21 While the utility of SmCl2 is narrowed due to limited solubility, SmBr2 has been used for reactions including reductive couplings, the reduction of aromatic hydrocarbons, and cyclizations.22–24 More recently, Procter has used SmBr2 in combination with H2O to efficiently perform cyclization cascade reactions that proceed through initial reduction of amide-type carbonyls.22 In that work, SmBr2-water was proposed to reduce substrates through a sequential ET-PT. Since SmBr2 has a more negative redox potential compared to SmI224 and is therefore a more powerful reductant, initial ET may be possible, but in the presence of coordinated water, PCET is possible as well.14 Given these suppositions, several questions arise: 1) How does the SmBr2 reagent system differ from the SmI2-H2O system? 2) Can coordinating proton donors be used in conjunction with SmBr2 to increase the reactivity in a manner similar to that observed for SmI2? 3) Does water displace bromide from the inner sphere of Sm(II) in a manner analogous to that of SmI2? 4) Since SmBr2 is a stronger reductant than SmI2, does the coordination of water lead to a greater degree of O-H bond weakening? 5) Do reactions of SmBr2-water proceed via a

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Characterization of the SmBr2-water system SmBr2 is a more powerful reductant than SmI2 and can be prepared via several different methods.20,25,26 The most straightforward approach has been employed in a number of synthetic studies and involves the addition of lithium bromide (LiBr) to a solution of SmI2.20 While lithium halides are soluble in THF, the lithium cation is a good Lewis acid and we were therefore concerned that it could alter the reactivity of the system. As an alternative, we employed tetrabutylammonium bromide (TBABr) instead of LiBr. Upon addition of 4 equivalents TBABr to a solution of SmI2, a red shift in the visible spectrum is observed consistent with the spectum obtained for SmBr2 generated from SmI2 and LiBr (see Supporting Information). The direct preparation of SmBr2 was performed via sonication of Sm metal and 1,1,2,2tetrabromoethane and the UV-vis spectrum was also obtained and was consistent with the generation of SmBr2 (see Supporting Information). With the TBABr-generated SmBr2 in THF characterized, we next examined the impact of water addition on the UV-vis spectrum. Previous studies on the SmI2-water system by our group demonstrated that water has a high affinity for SmI2 even in bulk THF.27,28 In addition, coordination of water to Sm(II) displaces iodide and bound solvent at relatively low concentrations,29 resulting in large changes in the UV-vis spectrum. To determine the impact of water addition to SmBr2, a series of UV-vis spectra were examined where the concentration of SmBr2 was maintained at 2.5 mM in the presence of increasing concentrations of water as shown in Figure 1. Similar shifts in the UV-vis spectra are observed, suggesting that water coordinates to SmBr2 in much the same way as it coordinates to SmI2. The main difference is that in the case of SmI2, a band begins to appear at 480 nm upon higher equivalents of water that is absent in the experiments with SmBr2.21

0 eq 10 eq 50 eq 100 eq 200 eq

0.5 0.4 0.3

Previous conductance studies have demonstrated that the addition of water to a solution of SmI2 displaces the iodides into the outer sphere even when a modest amount of water has been added.29 These studies showed that the addition of water had no impact beyond coordination to Sm(II) at low concentrations but the conductance of the solution began to increase after the addition of about 20 equivalents of water. Increasing the amount of water beyond 20 equivalents led to increased conductance consistent with the initiation of iodide displacement from the inner sphere. This experimental finding is supported by recent studies of Ramírez-Solís and coworkers who employed BOMD simulations demonstrating the liberation of iodide ligands from the inner-sphere of SmI2 upon solvation by water.30 To further examine the SmBr2-water system, a series of experiments were performed where the conductance of the SmBr2 solution was measured upon increasing amounts of water. For these experiments, SmBr2 was prepared directly using sonication to avoid the addition of a strongly conducting alkyl ammonium salt in solution. When conductance experiments with SmBr2 containing increasing amounts of water were carried out, only a slight increase in conductance was observed at 100 equivalents of water. This indicates that it is unlikely that bromides are displaced by water at this concentration. Conductance experiments for SmI2 and SmBr2 are shown in Figure 2. These experiments demonstrate that the modest change of halide from iodide to bromide has a reasonable impact on the type of reductant formed in solution. Upon the addition of water to SmI2, it is likely that a cationic Sm(II) with the general form of [Sm(H2O)x]2I- is formed29 whereas in the case of SmBr2, the bromides remain in the inner sphere. One question that arises is: What is the speciation of SmBr2-water and does this impact the reactivity of the reagent system?

Conductivity (microS)

PCET mechanism? Herein we address these questions and the work reveals differences between the reagent systems that have a large impact on the reactivity in spite of the modest change in halide.

Absorbance

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Page 2 of 10

2 1.5 1 0.5 0 0

50

100

150

200

equivalents water

0.2 0.1

Figure 2. Plot of the conductivity of 2.5 mM of SmI2 () and SmBr2 () with increasing amounts of H2O.

0 300

400 500 600 Wavelength (nm)

700

Figure 1. UV-vis spectra of 2.5 mM SmBr2 in the presence of increasing amounts of water (10, 50, 100, 200 equivalents vs SmBr2).

Computational studies To address the aqueous solvation of SmBr2 through the solvation process and learn more about the speciation of the active reductant, Born-Oppenheimer molecular dynamics (BOMD) Density Functional theory simulations were performed on the SmBr2-(H2O)32 model system and compared to the SmI2-(H2O)32 reagent system. The BOMD-DFT molecular dynamics simulations were carried out with the


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Geraldyn2.1 code,31 which has been coupled to the electronic structure modules of GAUSSIAN-09.32 The BOMD simulations used exactly the same conditions previously applied for the microhydrated SmI230 and the computational details are given in the SI material. The BOMD simulation started from a slightly modified initial microsolvated structure (also given in the SI) of the one we previously used for SmI230 and the initial Sm-Br distance was taken from the optimized SmBr2 molecule, Re(Sm-Br)=2.85 Å without any preferred velocity vectors other than the thermal energy using a Boltzmann distribution at 300K. The production run was started following an initial thermalization period of 10 ps. Reliable data were extracted from the last 10 ps of the simulation to perform the statistical analysis; the Sm-O, SmBr, Sm-H, Br-H, Br-O radial distribution functions and the EXAFS spectrum were also obtained. A. Theoretical EXAFS spectrum. To produce the EXAFS spectrum (L3 edge) from the molecular dynamics simulation, we followed same the procedure as the one we used previously to address the aqueous solvation of As(OH)3,33 HgCl2,34 SmI230 and SmI335 which, in turn, is based on the one originally presented by Merkling et al.36 The EXAFS spectrum was calculated as an average of the spectra produced by a number of system configurations obtained during the simulation, thus incorporating the disorder factor (the Debye-Waller factor) naturally occurring in the experiment. After thermalization was achieved (10 ps), 500 snapshots each separated by 200 configurations were used to obtain the theoretical EXAFS spectrum. A cutoff centered around the Sm atom was applied to each structure in order to include water molecules whose oxygen atoms lie at distances up to 5.0 Å, and paths with lengths up to this value were included considering multiple scattering. The EXAFS calculations were performed using the FEFF program39 (version 9.03) with an amplitude reduction factor S02 =1. B. Analysis of BOMD Simulation The BOMD simulation for SmBr2 started from a slightly modified initial microsolvated structure of the one we previously used for SmI2 and can be found in the Supplementary Information (Fig. S14). Figure 3 shows a typical structure of the microsolvation pattern around Sm after thermalization has been achieved

Figure 3. Typical microsolvation pattern for the SmBr2-(H2O)32 system at 300K after thermalization has been achieved. Sm (yellow), oxygen (red spheres), bromine atoms (green spheres).

Since the simulations for SmI230 and SmBr2 were done using the same microsolvation conditions, it is of interest to compare the evolution of the Sm-Br vs. Sm-I distances for the SmX2(H2O)32 systems after thermalization has been achieved; Figure 5 shows this comparison. The results reported in Figure 4 a)

b)

Figure 4. Evolution of the Sm-Br (a) and Sm-I (b) distances for the SmX2-(H2O) 32 systems at 300K. Note the different scales and the higher oscillation frequency of the bromide ions due to confinement between the first and second solvation shells.

reveal a dramatic difference in the behavior of the halogens with respect to the Sm(II) center under the same simulation conditions. Figure 4 shows that, while for SmI2 a rather rapid dissociation of the Sm-I bonds takes place, one of the iodide ions remains relatively close to the Sm(II) center (ca. 3.6Å) while the other is ejected from the first solvation shell and remains at an average distance of 5.5 Å, which leads to an overall water coordination number CN=8.430 around Sm(II). On the other hand, for SmBr2 although the bromide ions dissociate from the Sm(II) cation, both of them remain at a significantly shorter average distance (3.3 Å) from Sm(II) allowing only three water molecules to take their place around Sm(II), thus leading to a smaller water coordination number CN=7.5. The Sm-O, Sm-Br and Sm-H radial distribution functions (RDFs) obtained from the last 20000 configurations are shown in Figure 5. In this case note that the first solvation shell


Journal of the American Chemical Society extends from 2.4 to ca. 3.3 Å and its integration leads to a coordination number CN=7.5 water molecules around the Sm(II) cation, nearly one less water molecule than what was found for the SmI2 case.30 The second solvation sphere is much broader extending from 3.3 to around 6 Å although, with only 32 water molecules in the present model, it is difficult to distinguish the limit between the second and the third solvation shells around Sm(II). Note the slight shoulder around 5.4 Å which could be indicative of the superposition of the second and third solvation shells in this case. An interesting finding concerns the rather narrow Sm-Br RDF, whose average distance is Sm-Br=3.3 Å and extends only from 2.95 to 3.8 Å. a)

8

7

Sm-O distances (angstroms)

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Page 4 of 10

6

5

4

3

2

0

1000

2000

3000

4000

5000 6000 Time (fs)

7000

8000

9000

10000

Figure 6. Evolution of the Sm-O distances for the SmBr2-(H2O)32 cluster leading to a water coordination number CN=7.5 below R(Sm-O)=3.3 Å. For comparison, the thick black curve between 3 and 4 Å corresponds to the oscillation of one of the bromide ions between the first and the second solvation shells.

b)

Figure 5. The upper panel shows the comparison of the Sm-O, Sm-Br and Sm-H radial distribution functions for SmBr2 (a) and SmI2 (b). The lower panel shows the corresponding coordination numbers as a function of distance from the Sm(II) center at 300K.

Figure 6 shows the temporal evolution of the shortest Sm-O distances. Here another important difference appears with respect to the microsolvated SmI2 system, where it was found that eight water molecules remain tightly bound inside a 3.3 Å sphere around Sm(II), and that a ninth molecule is intermittently coordinated to Sm(II).30 In the microsolvated SmBr2 case we find that only 7 water molecules remain tightly bound inside a smaller 3.0 Å sphere around Sm(II) and that, on average, an eighth molecule is intermittently coordinated to Sm(II).

Although both Sm-Br average distances (3.3 Å) in the microsolvated system are much longer than the Sm-Br equilibrium distance of the isolated molecule (2.85 Å), it is interesting to note that the Br-Sm-Br average angle remains close to that of the isolated molecule, (ca. 130º) and a careful analysis of the evolution of the Sm-O and Sm-Br distances revealed why this is so. In the present case we have found that both bromide ions remain “trapped” between the first and the second solvation shell of Sm(II) (thus allowing for relatively small oscillations of the Br-Sm-Br angle in the time scale we explored here), while for SmI2 case one of the iodides is completely displaced and moves out to become part of the second solvation shell therefore losing all the angular correlation with the other iodide anion.30 In order to rationalize the lower activity of SmBr2 vs. that of SmI2 for RET reactions in the light of the present dynamical results, we have performed a full geometry optimization of the SmBr2-(H2O)32 system starting from the lowest energy structure found during the last 10 ps of the BOMD simulation and performing an equivalent optimization for the SmI2(H2O)32 system. Figure 7 shows the optimized microsolvated systems in each case at the same level of theory as that used for the BOMD trajectories (see SI).

Figure 7. Optimized geometries for the microsolvated SmBr2(H2O)32 (left) and SmI2-(H2O)32 (right) systems. While for SmI2 six water molecules are coordinated to Sm(II), for microsolvated SmBr2 only five water molecules interact with the metal center.


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Four quantities of interest arise for comparison of the optimal microsolvated SmX2-(H2O)32 systems: the Sm-X optimized distances, the associated CN number of Sm-bonded water molecules, the total water binding energies as previously defined in ref. [28] and the atomic charges of the Sm and of the halogen ions as determined by Natural Population Analyses. Table 1 summarizes these quantities for the optimized microsolvated SmX2-(H2O)32 clusters. Table 1. Summary of important quantities determined for the optimized SmX2-(H2O)32 systems. Parameter

SmBr2-(H2O)32

SmI2-(H2O)32

Optimized Sm-X distances (Å):

3.04, 3.16

3.32, 3.38

Water coordination number (CN):

5

6

Total binding energies (kcal/mol):

-18.42

-17.74

NPA Charge Sm

0.859

0.744

NPA Charge X1

-0.697

-0.628

NPA Charge X2

-0.673

-0.607

Note that while for the optimal microsolvated SmI2 structure six water molecules are coordinated to Sm(II), for the optimal microsolvated SmBr2 only five water molecules interact with the Sm(II) center. This fact is related to the larger ionic radius of iodide vs. that of bromide; noteworthy is also the smaller natural charge on the iodides (ca. 0.63e) than on bromide ions (ca. 0.70e) for the optimized structures. The present calculated EXAFS spectrum obtained from the last 10 ps of the BOMD simulation is shown in Figure S16 in the Supplementary Information. Unfortunately, to the best of our knowledge, no experimental EXAFS data have been reported for SmBr2 in water, so that we can only qualitatively compare our theoretical prediction with that obtained for the SmI2 case30 and with the EXAFS spectrum obtained for Sm(III)35. Further discussion is provided in the supporting information. Overall, the data from BOMD simulations at 300K provide clear evidence of key differences between SmI2-water and SmBr2-water. The theoretical EXAFS spectrum shows significant differences when compared to the one previously obtained for SmI2. These differences are explained in terms of: a) the different local dynamic hydration patterns for SmBr2 vs. SmI2 and, b) the larger charge of Br vs. I in the lowest energy optimized SmX2-(H2O)32 complexes (which is related to the larger electron affinity of Br), and the larger total binding energy for the former, thus preventing a full effective dissociation of the Sm2+ + 2Br- ions in the microsolvation environment. The important question that remains from the BO molecular dynamics studies is: what is the impact on the reactivity of SmBr2-water in comparison to SmI2-water given the differences in solvation and speciation? Rate studies Sm(II)-water reactions are extremely complex due to the potential for coordination of proton donor, substrate, and solvent to the metal, making mechanistic studies complicated. Use of a non-coordinating substrate such as anthracene simplifies the system allowing us to further examine the

impact of water on both the reducing power of the Sm complex and reaction rates. The use of this non-coordinating substrate also allows for the direct comparison of the reduction of anthracene by SmBr2-water and SmI2-water, a previously studied and well–characterized system that has been demonstrated to proceed via a PCET mechanism. The comparison is also important since SmBr2 is a thermodynamically more powerful reductant. As a consequence, it is possible that a stepwise ET-PT is possible even though PCET provides a lower energy pathway for reduction.37 To examine the system in detail and gain insight on the discussion vide supra, a series of reactions were performed on SmBr2-mediated reductions of anthracene using water, methanol (MeOH), and isopropyl alcohol (IPA) over a wide range of concentrations (0-8 M for water and 0-2 M for MeOH and IPA) in THF as shown in equation 1. Alcohols were chosen that have pKa values similar to water. Reactions without proton donor led to reduction of anthracene over a several day period. Reduction of anthracene with MeOH and IPA proceeded to product but were considerably slower than with water, typically taking a day to complete.

To further investigate the reduction mechanism of the SmBr2-H2O system, kinetic studies were performed and rate orders were determined. Rate studies were performed under pseudo-first order conditions with anthracene in an excess with respect to [SmBr2] which was maintained at 10 mM. The reaction was monitored using stopped-flow spectrophotometry to observe the loss of absorbance of Sm(II) at 540 nm. It is important to note that SmBr2 prepared from SmI2 and TBABr was used for these studies for ease of preparation. Several rate experiments were performed with SmBr2 and results were within experimental error. Water concentrations were varied over a range of 33 mM to 8 M with constant concentrations of SmBr2 and substrate. Each rate measurement was repeated thrice with freshly prepared samples. To verify that the rate of substrate reduction was not influenced by the instability of the SmBr2-water complexes at high concentrations of proton donor, the natural decay of the complex was acquired and found to be < 10% of the value obtained for the decay of Sm(II) in the absence of substrate. Rate orders for SmBr2, water, and anthracene were determined for each of the components and are shown in Table 2. The rate Table 2. Rate Orders for Reduction of Anthracene by SmBr2Water Reaction Component

Rate Order

SmBr2

1.1a

Anthracene

1.2  0.1 b

Water

2.0  0.1c

Conditions: aFractional times method. 10 mM SmI2, 100 mM anthracene, 0.75−2 M H2O. b10 mM SmBr2, 60−100 mM anthracene, 330 mM H2O. c10 mM SmBr2, 100 mM anthracene, 0−0.75 M H2O. The rate orders are the average of three independent experiments.



of the concentration of THF in solution. Overall, the deuterium KIE data is consistent with a primary kinetic isotope effect whose magnitude is a consequence of PCET and is in agreement with other KIE values obtained for systems that proceed via a PCET mechanism.14 3 25

2.5

0.45 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 0

20

kH/kD

2

15

1.5

10

1

5

0.5 kH/kD

Polarity

0

0

5

10

0 0

15

Dielelctric of THF/H2O Mixture

order of water was obtained from the nonlinear region of the plot of kobs vs [water] up to 1M. The rate orders of anthracene and SmBr2 are near unity, whereas water displays a rate order of 2 under synthetically-relevant concentrations up to 1 M. The rate constant for the reduction of anthracene was found to be 6.7 x 102 M-3s-1. A plot of kobs vs water concentration up to

Average kobs (s-1)

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Page 6 of 10

2

4 [Water] (M)

6

8

[ H2O] (M) Figure 8. Plot of kobs vs. water concentration for the reduction of 100 mM anthracene by 10 mM SmBr2 (, blue) and SmI2 (, red).

8 M for the reduction of anthracene by SmBr2 and SmI2 is shown in Figure 8. The water curve for the SmBr2-H2Oanthracene system displays a similar shape to the water curve obtained for the SmI2-H2O-anthracene system but proceeds at about 3 times the rate. A saturation point at a much lower [H2O] is also observed with the SmBr2-water system. We attribute the lower saturation point for the SmBr2-water system to be a consequence of bromide remaining bound to the inner sphere leading to coordinative saturation by water at lower concentrations compared to SmI2 where the iodides are displaced. To obtain further insight into the mechanistic role of water in the SmBr2-mediated reduction of anthracene, rates were measured using D2O over a range of concentrations to determine the kH/kD. A plot of the kH/kD vs water concentration is shown in Figure 9. Although an average kinetic isotope effect (KIE) of 1.5 was obtained from 3 trials over the range of 0.33M to 8M water, there is a clear trend showing that the kH/kD ratio increases slightly with increasing [H2O]. We hypothesize the reason for this shape of KIE curve is due to the proximity of bromide ions to the samarium metal center. With our conductivity experiment we demonstrated that the bromide ions are bound to the samarium metal center until roughly 100 equivalents of water are added. In the KIE graph we see an increase in the kH/kD from 0 M to 1 M water. With increasing concentrations of water, the coordination between samarium and bromide ions is likely weakened while coordination between water and samarium is enhanced, creating a greater difference between the energy required for the O-H vs O-D bond cleavage and therefore an increase in kH/kD from 0 to 1 M water is observed. At the point of 1 M water (100 equivalents) where the bromide ions begin to liberate, the kH/kD values stabilizes. Beyond approximately 4 M water the kH/kD value begins to increase. We attribute this observation to a solvent medium effect. This supposition is supported by the computed dielectric of THF/water as shown in Figure 9. At this point the concentration of water rivals that

Figure 9. Plot of kH/kD vs [water] for the reduction of anthracene by SmBr2. [SmBr2] = 10 mM; [anthracene] =100 mM () and [water] vs. dielectric of THF/water ().

To acquire further information about the reduction of anthracene by SmBr2 and water, rates were determined over a 20° C temperature range to obtain activation parameters from the linear form of the Eyring equation. This data is shown in Table 3. The concentrations of water were maintained at 0.33 M (33 equivalents), which is the region where water exhibits a rate order of 2, and 1 M (100 equivalents), a concentration typically employed in synthesis. Examination of the data in Table 3 shows that the reaction proceeds through an ordered activated complex with a relatively low barrier to bond reorganization. In addition, these findings are consistent with a PCET based on comparison with similar systems.14,38–42 Table 3. Activation Parameters for the Reduction of Anthracene by SmBr2 and Water [H2O]a

ΔH⧧b

ΔS⧧b

ΔG⧧c

(kcal/mol)

(cal/mol*K)

(kcal/mol)

0.33 M

4.2

-51

19.4

1.0 M

5.0

-46

18.0

Conditions: 10 mM SmBr2 and 100 mM anthracene in THF. The activation parameters are the average of three independent experiments from 15 to 35 °C and are reported as ± σ. bObtained from ln(kobsh/kT) − ΔH⧧/RT + ΔS⧧/R. c Calculated from ΔG‡ = ΔH⧧ − TΔS⧧. a

The data up to this point show that the SmBr2-water system reduces anthracene faster than SmI2-water consistent with SmBr2 being a more powerful reductant, but how does it differ from SmBr2 containing proton donors such as alcohols that likely do not coordinate with high affinity. Since SmBr2 is a powerful reductant, an ET-PT mechanism should be feasible when used in concert with a proton donor such as an alcohol. To test this supposition, the rate of anthracene reduction by SmBr2 containing MeOH and IPA were obtained over a large concentration range to compare directly to the SmBr2-water system as shown in Figure 10.


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Average kobs (s-1)

Page 7 of 10 0.5

MeOH

0.4

IPA

0.3

Water

the value determined by Mayer and Kolmar employing thermochemical cycles19 and further demonstrates that the combination of SmBr2 and water is able to form even weaker C-H bonds than SmI2-water. Scheme 1. Estimate of the degree of O-H bond weakening upon coordination of water to SmBr2 in THF.

0.2 0.1 0 0

2

4

6

8

[Proton Donor] (M)

10

Figure 10. Plot of kobs vs proton donor concentration for the reduction of anthracene by SmBr2.

Inspection of Figure 10 shows clear differences between the SmBr2-water and alcohol systems. The rate of reduction of anthracene by SmBr2-water proceeded at a rate more than two orders of magnitude faster than with either isopropanol or methanol. The drastic difference in rates observed between a coordinating proton donor capable of facilitating a PCET mechanism such as water versus a non-coordinating proton donor such as an alcohol not known to facilitate PCET further demonstrates that reduction of anthracene by SmBr2-H2O proceeds via a PCET mechanism. In addition, the data demonstrate that a sequential ET-PT reduction is possible, albeit at much lower rates. Interestingly, the rate is impacted very little by [alcohol] suggesting that ET is rate-limiting. With these studies in hand, we wanted to examine the limit of reduction possible with SmBr2-water. A series of arenes including anthracene, stilbene, and phenanthrene were examined. We found that a small amount of reduction of phenanthrene occurred, but arenes with more negative reduction potentials were not reduced (see SI). All of the data described to this point is consistent with bond-weakening of water as a consequence of coordination to SmBr2 in THF. To estimate the degree of bond-weakening upon coordination of water to SmBr2, the bond dissociation free energies (BDFE’s) in THF for the O-H bond of water and the intermediate radical formed upon formal hydrogen atom transfer to phenanthrene were calculated using density functional calculations43,44 as described in previous publications.15–18 Subtraction of the C-H BDFE from the arene radical provides an estimate of the minimum degree of bondweakening required for formation of the C-H bond in the reduction of phenanthrene. Substantial bond-weakening of the O-H bond of water was thus estimated to be at least 83 kcal/, providing a BDFE for water bound to SmBr2 of approximately 25 kcal/mol.14 Bond-weakening of ligands bound to low-valent metals is well-established in the PCET literature. It is observed with coordination of water, ammonia and other ligands to low valent metal complexes including titanium, zirconium, cobalt, and copper.45–49 These bond-weakening processes can lead to significant weakening of O-H, N-H, and even C-H bonds. Among low-valent Sm complexes, work in our group has established that coordination of water to SmI2 leads to significant bond weakening of approximately 73 kcal/mol.14 The data in Scheme 1 show that the more highly reducing SmBr2 weakens the O-H bond of water by an additional 9 kcal/mol. This estimate of bond-weakening is consistent with

Since SmBr2 is a stronger reductant than SmI2, the enhanced bond weakening of coordinated water is unsurprising, but raises the questions: 1) How stable are these reagents and 2) Can even weaker O-H bonds be formed with other Sm(II)based reductants? To test the latter question, samarium dichloride (SmCl2) was produced via the reaction of SmI2 with LiCl and tetrabutylammonium chloride as described above. This reagent is a stronger reductant than SmBr2.24 While the reagent was stable in THF, upon addition of water a reaction occurred instantaneously producing a gas identified as hydrogen by 1H NMR. To probe this further, a 0.1 M solution of either SmI2 or SmBr2 was placed in a test tube fitted with a pressure sensor and 200 equiv of water based on [Sm(II)] was added and the pressure was monitored over time to follow the rate of gas evolution. Under these conditions, H2 gas was evolved from SmBr2 over a period of 600-700 seconds, whereas the same reaction with SmI2 evolved H2 gas over a period of 4000 seconds (See SI). The faster rate of hydrogen production from SmBr2-water demonstrates that this complex is less stable than the corresponding SmI2-water complex. In all reactions examined, the substrate is added to Sm(II) and then the water is added leading to reduction of substrates. In the case of SmCl2, addition of water to a solution of the reagent and substrate led to incomplete conversion due to competitive reduction of water. These experiments suggest that at room temperature, the combination of SmBr2 and water is likely the practical limit for a Sm(II)-water based reducing system. More potent Sm(II)-based reductants are likely too reactive to be used with water, at least under the ambient conditions examined in this study. Conclusions The data presented herein demonstrates that the addition of water to SmBr2 provides a very reactive reducing system. Although there are similarities between the SmI2-water and SmBr2-water reducing systems, addition of water to SmBr2 does not liberate bromide ions to the extent that occurs upon addition of water to SmI2 as demonstrated by spectroscopic, conductance and computational studies. Thus, the relatively modest change in halide has a large effect on reactivity, providing a unique reductant that reduces anthracene three times faster than SmI2-water under the same conditions. The inclusion of water in the empirical rate law is consistent with a


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role in the rate-limiting step and a deuterium KIE value consistent with a primary kinetic isotope effect. The coordination of water to SmBr2 leads to significant O-H bondweakening of over 80 kcal/mol that leads to substrate reduction through PCET. Interestingly, addition of alcohols that do not coordinate to SmBr2 still facilitate the reduction of anthracene, but reactions are several orders of magnitude slower than those using water and likely occur through a ratelimiting ET. Overall, the importance of proton donor coordination demonstrates that this approach can be used to create relatively weak C-H bonds and that water can be employed to generate intermediate radicals through PCET that are not accessible via sequential ET-PT. Finally, proton/reductant compatibility is often times a limiting feature of this class of reactions. In the examples studied herein, evolution of H2 from the Sm(II)-water complexes should have a significant thermodynamic driving force, yet gas evolution is relatively slow from SmI2-water and increases as iodide ligands are replaced by bromide and chloride to produce stronger reductants. Beyond reductant driving force, there is likely a kinetic barrier to hydrogen evolution of bound water. We are currently examining the origin of this stability since this unusual feature may be adapted to other systems and the results of these studies will be reported in due course.

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ASSOCIATED CONTENT Supporting Information General experimental methods, spectroscopic, rate, and computational data. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION (16)

Corresponding Authors *[email protected], *[email protected]

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Author Contributions The manuscript was written through contributions of all authors who have given approval to the final version of the manuscript.

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Notes The authors declare no competing financial interests.

ACKNOWLEDGMENTS RAF is grateful to the National Science Foundation (CHE1565741) for support of this work. ARS thanks support from CONACYT Basic Science project number 253679. HSM thanks financial support from DGAPA-UNAM grant No. IN101599. JHC thanks support from DGAPA-UNAM grant No. IG100416.

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Experimental and Theoretical Studies on the Implications of Halide

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