Layered Double Hydroxides As Bifunctional Catalysts for the Aryl Borylation Under Ligand-Free Conditions

catalysts

Communication Layered Double Hydroxides as Bifunctional Catalysts for the Aryl Borylation under Ligand-Free Conditions

Lorenna C. L. L. F. Silva 1, Vinícius A. Neves 1, Vitor S. Ramos 2, Raphael S. F. Silva 3, José B. de Campos 2, Alexsandro A. da Silva 4, Luiz F. B. Malta 1,* and Jaqueline D. Senra 1,4,*

1 Laboratório de Química Supramolecular e de Sólidos, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil; [email protected] (L.C.L.L.F.S.); [email protected] (V.A.N.) 2 Faculdade de Engenharia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-900, Brazil; [email protected] (V.S.R.); [email protected] (J.B.d.C.) 3 Instituto Federal do Rio de Janeiro, Campus Rio de Janeiro, Rio de Janeiro 20270-021, Brazil; [email protected] 4 Instituto de Química, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-900, Brazil; [email protected] * Correspondence: [email protected] (L.F.B.M.); [email protected] (J.D.S.); Tel.: +55-21-3938-7738 (L.F.B.M.); +55-21-2334-0563 (J.D.S.) Received: 29 January 2019; Accepted: 18 March 2019; Published: 27 March 2019

Abstract: Organic derivatives of boron, such as boronic esters and acids, are important precursors for a wide range of environmental, energy, and health applications. Several catalytic methods for their synthesis have been reported, even though with the use of toxic and structurally complex ligands. Herein, we demonstrate preliminary studies envisaging the synthesis of boronic esters from an inexpensive catalytic system based on Cu/Al layered double hydroxides (LDH) in the presence of Na2PdCl4. The Cu/ Al LDHs were prepared according to coprecipitation method and characterized by X-ray diffraction (XRD) (with Rietveld reﬁnement) to evaluate the contamination with malachite and other phases. Preliminary catalytic results suggest that pure Cu/Al LDH has potential for the borylation of aryl iodides/ bromides in the absence of base. Indeed, a synergic effect between copper and palladium is possibly related to the catalytic efﬁciency.

Keywords: boronic esters; borylation; Suzuki–Miyaura; layered double hydroxides; copper; palladium

1. Introduction Organoboron compounds have received great attention in last years due to signiﬁcant impact in analytical [1], technological [2], and medicinal ﬁelds [3]. Particularly, low-weight compounds containing boronic acid/ester moieties have played an important role in the synthesis of new hybrid materials, sensors and complex organic molecules, through synthetic protocols such as Suzuki–Miyaura reactions. However, mild and selective synthesis of boronic acids and esters still represent a challenge. In general, the classic reactions involving the generation of organometallics (e.g., arylmagnesium or aryllithium) followed by the reaction with a borate have been substituted by catalytic protocols [4]. Recently, new methods involving metal-free conditions have also been discovered [5,6]. However, most of them suffer from low reactivity/selectivity along with relatively high costs of the boron reagents. Some advantages of the catalytic protocols are the improved reaction selectivity and the possibility of the whole system reuse. Since the general steps for the catalytic synthesis of boronic acids and esters involve a sequence of oxidative addition and reductive elimination, several

Catalysts 2019, 9, 302; doi:10.3390/catal9040302 www.mdpi.com/journal/catalysts Catalysts 2019, 9, x FOR PEER REVIEW 2 of 12

Catalysts 2019, 9, 302 2 of 12 In 1995, Miyaura first reported the Pd‐catalyzed aryl borylation protocol by using a phosphine‐ based catalyst—Pd(dppf)Cl2—in the presence of KOAc for the activation of diboron reagent [8]. Since semihomogenousthen, several efficient or heterogeneous methodologies systems have been are reported described based based on on similar the employment reaction conditions of noble metals[9–11]. (e.g.,Recently, Pd and Ratniyom Ir) as catalysts and coworkers [7]. [12] reported an efficient cooperative catalysis based on Pd(0)/Cu(I)In 1995, in Miyaurathe presence first of reported triphenylphosphine the Pd-catalyzed with good aryl results borylation towards protocol aryl iodides by using and a phosphine-basedbis(pinacolate)diboron. catalyst—Pd(dppf)Cl However, the yields2—in were the very presence sensitive of KOAc to the nature for the of activation the base and of reduced diboron reagentdrastically [8]. with Since the then, use severalof aryl bromides/chlorides. efficient methodologies have been reported based on similar reaction conditionsInorganic [9–11 networks]. Recently, with Ratniyom basic properties and coworkers represent [12 one] reported alternative an efficient to avoid cooperative the use of expensive catalysis basedligands on as Pd(0)/Cu(I) well as strong in bases the presence in order of to triphenylphosphine achieve the B–B bond with activation. good results Mostly, towards bimetallic aryl systems iodides andusually bis(pinacolate)diboron. involve low loadings However,of a noble themetal yields in combination were very sensitive with an early to the transition nature of metal the base to allow and reduceda cost‐effective, drastically broader with functional the use of arylgroup bromides/chlorides. tolerance, and scalable reaction condition. Layered double hydroxidesInorganic (LDHs)—anionic networks with clays basic also properties known represent as hydrotalcites—have one alternative a to structure avoid the based use of on expensive layers of ligandsbi‐ and trivalent as well asmetals strong hydroxides bases in and order interlayer to achieve spaces the occupied B–B bond by activation. anions and Mostly,neutral molecules bimetallic systems[13], see Figure usually 1. involveThey can low be composed loadings of of a wide noble range metal of in different combination metals with and anions, an early which transition make metalthem touseful allow as a cost-effective,anionic exchangers, broader functionalflame retardants, group tolerance, catalysts, and and scalable supports reaction for condition. metallic Layerednanoparticles double [14], hydroxides and have (LDHs)—anionic low‐cost of synthesis clays also and known basic surface as hydrotalcites—have properties [15]. aSilva structure and basedcoworkers on layers [16] ofpreviously bi- and trivalent reported metals a catalyst hydroxides system and interlayerbased on spaces Mg/Al occupied LDHs, byPdNPs, anions and neutralcyclodextrins molecules for the [13 efficient], see Figure Suzuki–Miyaura1. They can bereaction composed between of a aryl wide bromides range of and different arylboronic metals acids. and anions,Lately, Sreedhar which make [17] employed them useful Cu/Al as anionic LDHs as exchangers, catalysts in flameUllmann retardants, reactions catalysts, between andaryl chlorides supports forand metallic amines. nanoparticlesSo far, cross‐coupling [14], and with have heterogeneous low-cost of synthesisligand‐free and Cu(II) basic based surface cocatalysts properties has [not15]. Silvabeen reported and coworkers to date in [16 borylation] previously reactions. reported a catalyst system based on Mg/Al LDHs, PdNPs, and cyclodextrinsIn the present for work, the efficient we disclosed Suzuki–Miyaura Cu/Al LDHs reaction as bifunctional between arylcocatalysts bromides in andthe arylboronicpresence of acids.Na2PdCl Lately,4 for Sreedharthe borylation [17] employed reactions Cu/Al between LDHs aryl as halides catalysts and in bis(pinacolato)diboron. Ullmann reactions between The arylkey chloridespoints examined and amines. here Soare far, the cross-coupling influence of withLDH heterogeneous purity and the ligand-free catalytic conditions Cu(II) based towards cocatalysts the hasreaction not been outcome. reported to date in borylation reactions.

Figure 1. Figure 1. Representation of layered double hydroxide (LDH) hydrotalcite-likehydrotalcite‐like structure, with the Cu/Al hydroxide layers and the carbonate containing interlayer space. Cu → green, O → red, H → Cu/Al hydroxide layers and the carbonate containing interlayer space. Cu → green, O → red, H → blue, blue, C → grey, Al → light red. C → grey, Al → light red. In the present work, we disclosed Cu/Al LDHs as bifunctional cocatalysts in the presence of 2. Results Na2PdCl4 for the borylation reactions between aryl halides and bis(pinacolato)diboron. The key points examined here are the inﬂuence of LDH purity and the catalytic conditions towards the 2.1. Synthesis and Characterization of Cu/Al LDH reaction outcome. A set of conditions were varied to accomplish the synthesis of the Cu/Al LDH. Figure 2 shows the X‐ray diffraction (XRD) patterns of samples obtained using or not sodium carbonate as an additive. These diffractograms were refined using the Rietveld method in order to obtain the

Catalysts 2019, 9, 302 3 of 12

2. Results

2.1. Synthesis and Characterization of Cu/Al LDH A set of conditions were varied to accomplish the synthesis of the Cu/Al LDH. Figure2 Catalystsshows 2019 the, 9, x X-ray FOR PEER diffraction REVIEW (XRD) patterns of samples obtained using or not sodium carbonate3 of 12 as an additive. These diffractograms were refined using the Rietveld method in order to obtain compositionthe composition of phases. of In phases. addition, In the addition, refinement the also refinement afforded alsothe unit afforded cell parameters the unit for cell LDH parameters phase: thesefor data LDH are phase: available these in the data supporting are available information in the supportingfile (Tables informationS1–S4). The LDH file (Tables synthesized S1–S4). withoutThe LDH sodium synthesized carbonate without (Figure sodium 2a) exhibited carbonate a XRD (Figure pattern2a) exhibited composed a of XRD reflections pattern composedfrom the mineralof reflections‐like phases from theof mineral-like gerhardtite phases (Cu(OH)NO of gerhardtite3, JCPDS (Cu(OH)NO‐ICDD 013, JCPDS-ICDD‐082‐1991), hydrotalcite 01-082-1991), (Mghydrotalcite0.67Al0.33(OH) (Mg2)(CO0.673Al)0.1650.33(H(OH)2O)0.482)(CO, JCPDS3)0.165‐ICDD(H2O) 010.48‐089, JCPDS-ICDD‐5434), and 01-089-5434),nitratine (NaNO and3 nitratine, JCPDS‐ (NaNOICDD 3, 00JCPDS-ICDD‐036‐1474). The 00-036-1474). LDH phase was The LDHobtained phase as wasa low obtained crystallinity, as a low minority crystallinity, phase with minority wide phase and low with ◦ ◦ intensitywide and peaks low at intensity 9.7° and peaks 19.9°. at The 9.7 Cu(OH)NOand 19.9 . The3 phase Cu(OH)NO (gerhardtite)3 phase was (gerhardtite) obtained as was the obtainedmajority as ◦ ◦ ◦ ◦ ◦ ◦ phasethe majoritywith the phase most withintense the mostpeaks intense at 12.7°, peaks 25.6°, at 12.733.9°,, 25.636.1°,, 33.940.4°,, 36.1and ,42.9°. 40.4 ,Finally, and 42.9 NaNO. Finally,3 ◦ (nitratine)NaNO3 (nitratine)was found was as another found asminority another phase, minority however phase, showing however a showingthin peak a at thin 2θ peak= 22.8°, at 2besidesθ = 22.8 , 29.4°,besides 31.8°, 29.4 and◦, 31.838.9°.◦, and 38.9◦.

(b) 30 000 Hydrotalcite 32.07 % 25 000 Malachite 34.15 % 20 000 Spertiniite 13.95 % Nitratine 19.83 % 15 000 10 000 5 000 0 Intensity(a.u.) -5 000 -10 000 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

(a) 16 000 Gerhardtite (deuterated) 71.65 % 14 000 Hydrotalcite 14.86 % 12 000 Nitratine 13.48 % 10 000 8 000 6 000 4 000 2 000 0 Intensity(a.u.) -2 000 -4 000 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

Figure 2. Rietveld-refined X-ray diffraction (XRD) patterns for Cu/Al LDH obtained (a) without and Figure(b) with 2. Rietveld Na2CO‐3refineddissolved X‐ray in thediffraction precipitation (XRD) agent patterns solution. for Cu/Al LDH obtained (a) without and (b)In with contrast, Na2CO Figure3 dissolved2b shows in the theprecipitation XRD pattern agent for solution. the sample synthesized using sodium carbonate. In this case, the majority phase was the layered double hydroxide with peaks at 2θ = 11.6◦, 23.5◦, 35.6◦, In contrast, Figure 2b shows the XRD pattern for the sample synthesized using sodium carbonate. 39.5◦, and 47.0◦. Another significant phase was malachite (Cu (OH) CO , JCPDS-ICDD 01-075-1163) In this case, the majority phase was the layered double hydroxide2 with 2peaks3 at 2θ = 11.6°, 23.5°, 35.6°, related to the peaks 2θ = 11.9◦, 14.7◦, 17.5◦, 24.0◦ 29.7◦, 31.7◦, 32.6◦, and 35.4◦. As minority phases, it 39.5°, and 47.0°. Another significant phase was malachite (Cu2(OH)2CO3, JCPDS‐ICDD 01‐075‐1163) was found that spertiniite (Cu(OH) JCPDS-ICDD 01-080-0656) related to peaks at 2θ = 16.7◦, 23.8◦, related to the peaks 2θ = 11.9°, 14.7°, 17.5°,2 24.0° 29.7°, 31.7°, 32.6°, and 35.4°. As minority phases, it 34.0◦, 35.9◦, and 39.8◦, and nitratine with peaks at 2θ = 22.8◦, 29.4◦, 31.8◦ and 38.9◦. was found that spertiniite (Cu(OH)2 JCPDS‐ICDD 01‐080‐0656) related to peaks at 2θ = 16.7°, 23.8°, Regarding the LDH unit cell parameters (Table S1, supporting information), both XRD were 34.0°, 35.9°, and 39.8°, and nitratine with peaks at 2θ = 22.8°, 29.4°, 31.8° and 38.9°. refined as having a rhombohedral crystal system and belonging to the R-3m spatial group. However, Regarding the LDH unit cell parameters (Table S1, supporting information), both XRD were the sample synthesized without carbonate presented the biggest unit cell dimensions (a = 3.039 Å and refined as having a rhombohedral crystal system and belonging to the R‐3m spatial group. However, c = 26.921 Å against a = 2.979 Å and c = 22.519 Å for the carbonate Cu/Al LDH), which means that an the sample synthesized without carbonate presented the biggest unit cell dimensions (a = 3.039 Å and expanded structural network was obtained. c = 26.921 Å against a = 2.979 Å and c = 22.519 Å for the carbonate Cu/Al LDH), which means that an The addition of sodium carbonate to the reaction medium allowed obtaining LDH as the main expanded structural network was obtained. phase, but did not avoid forming malachite, a by-product. Still, it was decided to use the carbonate The addition of sodium carbonate to the reaction medium allowed obtaining LDH as the main salt dissolved in the precipitation agent solution in the fore coming tests. phase, but did not avoid forming malachite, a by‐product. Still, it was decided to use the carbonate salt dissolved in the precipitation agent solution in the fore coming tests. In the next set of experiments the LDH precipitation pH and postsynthesis work‐up were evaluated. The precipitation pH was varied between two values, 8 and 10, which are the most used in LDH synthesis. The XRD patterns for both samples are presented in Figure 3. Figure 3a evidences the refined XRD pattern for the LDH precipitated at pH = 8, which, compared to that of Figure 3b, related to LDH precipitated at pH = 10; thus pH is not a significant parameter in the synthesis. This is also

Catalysts 2019, 9, 302 4 of 12

In the next set of experiments the LDH precipitation pH and postsynthesis work-up were evaluated. The precipitation pH was varied between two values, 8 and 10, which are the most used in LDH synthesis. The XRD patterns for both samples are presented in Figure3. Figure3a evidences Catalyststhe reﬁned 2019, 9, x XRD FOR PEER pattern REVIEW for the LDH precipitated at pH = 8, which, compared to that of Figure4 of 123b, related to LDH precipitated at pH = 10; thus pH is not a signiﬁcant parameter in the synthesis. This is supportedalso supported by strong by strong similarities similarities of unit of unitcell dimensions cell dimensions between between these these two two samples samples (Table (Table S2, S2, supportingsupporting information). information). Therefore, Therefore, a pH a pH of of8 was 8 was chosen chosen as as the the working working pH pH in in the the next next tests. tests.

(b)

25 000 Hydrotalcite 34.10 % Malachite 28.19 % 20 000 Spertiniite 13.88 % 15 000 Nitratine 23.83 %

10 000

5 000

Intensity(a.u.) 0

-5 000

6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

(a) 30 000 Hydrotalcite 32.07 % 25 000 Malachite 34.15 % 20 000 Spertiniite 13.95 % Nitratine 19.83 % 15 000 10 000 5 000 0 Intensity(a.u.) -5 000 -10 000 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

Figure 3. Rietveld-refined XRD patterns for Cu/Al LDH obtained at (a) pH = 8 and (b) pH = 10. Figure 3. Rietveld‐refined XRD patterns for Cu/Al LDH obtained at (a) pH = 8 and (b) pH = 10. In all experiments the LDH postsynthesis work-up proceeded using centrifugation, but one sampleIn all was experiments isolated using the filtration.LDH postsynthesis Their refined work XRD‐up patterns proceeded are shown using in centrifugation, Figure4. Concerning but one the sampleunit cell was dimensions, isolated using no significant filtration. differencesTheir refined between XRD patterns these two are samples shown canin Figure be perceived 4. Concerning (Table S3, thesupporting unit cell dimensions, information) Asno evidencedsignificant when differences nitratine between phase percentages these two aresamples compared can be the perceived centrifuged (Tablesample S3, (Figuresupporting4a) it information) exhibits 5-fold As moreevidenced NaNO when3 than nitratine the filtrated phase solidpercentages (Figure are4b), compared which implies the that the postsynthesis work up is an important parameter to be aware of. centrifuged sample (Figure 4a) it exhibits 5‐fold more NaNO3 than the filtrated solid (Figure 4b), which impliesTo reinforce that thatthe postsynthesis postsynthesis stepswork are up veryis an important important one parameter last sample to be was aware synthesized of. following the conditions established in the present study; however, this LDH was submitted to washing, using organic solvents (EtOH/Acetone). Its refined(b) XRD measurements are presented in the Figure5. The35 calculated 000 unit cell parameters show no significant differences from those previouslyHydrotalcite 47.61 shown % 30 000 Malachite 31.90 % (Table25 000 S4, supporting information). In the phase distribution it is clearly observed thatSpertiniite the malachite15.98 % % 20 000 Nitratine 4.51 % dropped15 000 from 31.93% (Figure4b) to 10.23% (Figure5), increasing LDH % from 47.92% to 65.70%. 10Besides, 000 the XRD peaks shown in Figure5 appear wider and less intense than those in Figure4b, 5 000

for instance.Intensity(a.u.) 0 According to the Full Width Half the Maximum (FWHM) criterium used in the Scherrer formula,-5 000 the mean crystal size evolved from 21 nm (for samples of Figures3 and4) to 14 nm, signaling 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 a decrease in crystallinity upon postsynthesis treatment,2Th Degrees such as washing with organic solvents. To evaluate the effect on the borylation reaction, catalytic tests were carried out by using malachite and LDH as catalysts. (a) 30 000 Hydrotalcite 32.07 % 25 000 Malachite 34.15 % 20 000 Spertiniite 13.95 % Nitratine 19.83 % 15 000 10 000 5 000 0 Intensity(a.u.) -5 000 -10 000 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

Figure 4. Rietveld‐refined XRD patterns for Cu/Al LDH obtained after (a) centrifugation and (b) filtration.

Catalysts 2019, 9, x FOR PEER REVIEW 4 of 12 supported by strong similarities of unit cell dimensions between these two samples (Table S2, supporting information). Therefore, a pH of 8 was chosen as the working pH in the next tests.

(b)

25 000 Hydrotalcite 34.10 % Malachite 28.19 % 20 000 Spertiniite 13.88 % 15 000 Nitratine 23.83 %

10 000

5 000

Intensity(a.u.) 0

-5 000

6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

Figure 3. Rietveld‐refined XRD patterns for Cu/Al LDH obtained at (a) pH = 8 and (b) pH = 10.

In all experiments the LDH postsynthesis work‐up proceeded using centrifugation, but one sample was isolated using filtration. Their refined XRD patterns are shown in Figure 4. Concerning the unit cell dimensions, no significant differences between these two samples can be perceived (Table S3, supporting information) As evidenced when nitratine phase percentages are compared the centrifugedCatalysts 2019 sample, 9, 302 (Figure 4a) it exhibits 5‐fold more NaNO3 than the filtrated solid (Figure 4b),5 of 12 which implies that the postsynthesis work up is an important parameter to be aware of.

(b) 35 000 Hydrotalcite 47.61 % 30 000 Malachite 31.90 % 25 000 Spertiniite 15.98 % 20 000 Nitratine 4.51 % 15 000 10 000 5 000

Intensity(a.u.) 0 -5 000

6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

(a) Catalysts30 000 2019, 9, x FOR PEER REVIEW Hydrotalcite 32.07 % 5 of 12 25 000 Malachite 34.15 % 20 000 Spertiniite 13.95 % Nitratine 19.83 % 15 000To reinforce that postsynthesis steps are very important one last sample was synthesized 10 000 following5 000 the conditions established in the present study; however, this LDH was submitted to 0 washing,Intensity(a.u.) using organic solvents (EtOH/Acetone). Its refined XRD measurements are presented in the -5 000 Figure-10 000 5. The calculated unit cell parameters show no significant differences from those previously 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 shown (Table S4, supporting information). In 2Ththe Degreesphase distribution it is clearly observed that the malachite % dropped from 31.90% (Figure 4b) to 10.13% (Figure 5), increasing LDH % from 47.61% Figure 4. Rietveld-reﬁned XRD patterns for Cu/Al LDH obtained after (a) centrifugation and to 66.03%. Figure(b) ﬁltration. 4. Rietveld‐refined XRD patterns for Cu/Al LDH obtained after (a) centrifugation and (b)

filtration.20 000 18 000 Hydrotalcite 66.03 % 16 000 Malachite 10.13 % 14 000 Spertiniite 13.51 % 12 000 Nitratine 10.33 % 10 000 8 000 6 000 4 000 2 000 Intensity(a.u.) 0 -2 000

6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 2Th Degrees

Figure 5. Rietveld-reﬁned XRD pattern for Cu/Al LDH obtained after washing with ethanol and acetone.

2.2.Figure Synthesis 5. Rietveld of Aryl‐refined Boronic XRD Esters pattern Employing for Cu/Al Cu/Al LDH LDHobtained Catalyst after washing with ethanol and acetone. The reaction between bis(pinacolato)diboron, (B(pin) ) and 1-iodo-4-nitrobenzene was taken as a Besides, the XRD peaks shown in Figure 5 appear wider2 and less intense than those in Figure 4b, model. Initially, purified Cu/Al LDH and malachite were evaluated as catalysts with acetonitrile as for instance. According to the Full Width Half the Maximum (FWHM) criterium used in the Scherrer solvent. From these data, it is possible to confirm that malachite did not show catalytic activity towards formula, the mean crystal size evolved from 21 nm (for samples of Figures 3 and 4) to 14 nm, signaling the borylation reaction. To evaluate the copper loading, we used the LDH composition according to the a decrease in crystallinity upon postsynthesis treatment, such as washing with organic solvents. method previously described by our group [18]. It was observed that both copper-based catalysts were To evaluate the effect on the borylation reaction, catalytic tests were carried out by using not able to catalyze the reaction (Table1, entries 1 and 2). Similarly, the use of Na PdCl as the sole malachite and LDH as catalysts. 2 4 catalyst was ineffective (Table1, entry 3). Indeed, addition of CuSO 4 in combination with Na2PdCl4 did not2.2. react Synthesis under of this Aryl condition Boronic Esters (Table 1Employing, entry 4). Cu/Al The comparison LDH Catalyst of the Pd precursor led us to evaluate a semihomogeneous system composed of palladium nanoparticles (PdNPs) stabilized by cyclodextrins (Table1The, entries reaction 5 and between 6). Our bis(pinacolato)diboron, research group have (B(pin) already2) describedand 1‐iodo this‐4‐nitrobenzene catalytic system was taken to the as carbon–carbona model. Initially, cross-coupling purified Cu/Al reactions LDH and [19]. malachite However, were it was evaluated not observed as catalysts significant with acetonitrile conversion as solvent. From these data, it is possible to confirm that malachite did not show catalytic activity even when using acetonitrile. Remarkably, the addition of 2 mol% Na2PdCl4 in the presence of LDH (30towards mol% Cu) the allowedborylation a yield reaction. of 98% To of theevaluate expected the product copper (Tableloading,1, entry we used 7). Since the theLDH positive composition effect couldaccording be related to the to method the LDH previously structural anddescribed compositional by our group properties, [18]. It we was also observed tested the that most both common copper‐ based catalysts were not able to catalyze the reaction (Table 1, entries 1 and 2). Similarly, the use of Mg/Al LDH in the presence of CuSO4 and Na2PdCl4, which rendered a good yield (Table1, entry 8). Na2PdCl4 as the sole catalyst was ineffective (Table 1, entry 3). Indeed, addition2 −of CuSO4 in Having in mind that the Cu/Al LDH is an anionic exchanger, it has been tested a [PdCl4] exchanged Cu/Alcombination LDH, and with surprisingly, Na2PdCl4 did the not yield react obtained under wasthis significantlycondition (Table lower, 1, 35%entry (Table 4). The1, entrycomparison 8). of the Pd precursor led us to evaluate a semihomogeneous system composed of palladium nanoparticles (PdNPs) stabilized by cyclodextrins (Table 1, entries 5 and 6). Our research group have already described this catalytic system to the carbon–carbon cross‐coupling reactions [19]. However, it was not observed significant conversion even when using acetonitrile. Remarkably, the addition of 2 mol% Na2PdCl4 in the presence of LDH (30 mol% Cu) allowed a yield of 98% of the expected product (Table 1, entry 7). Since the positive effect could be related to the LDH structural and compositional properties, we also tested the most common Mg/Al LDH in the presence of CuSO4 and Na2PdCl4, which rendered a good yield (Table 1, entry 8). Having in mind that the Cu/Al LDH is an anionic exchanger, it has been tested a [PdCl4]2− exchanged Cu/Al LDH, and surprisingly, the yield obtained was significantly lower, 35% (Table 1, entry 8).

Table 1. Survey of reaction condition.

O I O O Cu (%), Pd (%) B + O B B O N Base, solvent 2 O O O N 80oC 2

1 2 3 Catalysts 2019, 9, x FOR PEER REVIEW 5 of 12

T20 35,000 Hydrotalcite 65.70 % 30,000 Malachite 10.23 % 25,000 Spertiniite 13.45 % 20,000 Nitratine 10.62 % 15,000 10,000 Counts 5,000

Intensity (a.u.) 0 -5,000 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 2Th Degrees

Figure 5. Rietveld‐refined XRD pattern for Cu/Al LDH obtained after washing with ethanol and acetone.

Besides, the XRD peaks shown in Figure 5 appear wider and less intense than those in Figure 4b, for instance. According to the Full Width Half the Maximum (FWHM) criterium used in the Scherrer formula, the mean crystal size evolved from 21 nm (for samples of Figures 3 and 4) to 14 nm, signaling a decrease in crystallinity upon postsynthesis treatment, such as washing with organic solvents. To evaluate the effect on the borylation reaction, catalytic tests were carried out by using malachite and LDH as catalysts.

2.2. Synthesis of Aryl Boronic Esters Employing Cu/Al LDH Catalyst

The reaction between bis(pinacolato)diboron, (B(pin)2) and 1‐iodo‐4‐nitrobenzene was taken as a model. Initially, purified Cu/Al LDH and malachite were evaluated as catalysts with acetonitrile as solvent. From these data, it is possible to confirm that malachite did not show catalytic activity towards the borylation reaction. To evaluate the copper loading, we used the LDH composition according to the method previously described by our group [18]. It was observed that both copper‐ based catalysts were not able to catalyze the reaction (Table 1, entries 1 and 2). Similarly, the use of Na2PdCl4 as the sole catalyst was ineffective (Table 1, entry 3). Indeed, addition of CuSO4 in combination with Na2PdCl4 did not react under this condition (Table 1, entry 4). The comparison of the Pd precursor led us to evaluate a semihomogeneous system composed of palladium nanoparticles (PdNPs) stabilized by cyclodextrins (Table 1, entries 5 and 6). Our research group have already described this catalytic system to the carbon–carbon cross‐coupling reactions [19]. However, it was not observed significant conversion even when using acetonitrile. Remarkably, the addition of 2 mol% Na2PdCl4 in the presence of LDH (30 mol% Cu) allowed a yield of 98% of the expected product (Table 1, entry 7). Since the positive effect could be related to the LDH structural and compositional properties, we also tested the most common Mg/Al LDH in the presence of CuSO4 and Na2PdCl4, which rendered a good yield (Table 1, entry 8). Having in mind that the Cu/Al LDH is an anionic exchanger, it has been tested a [PdCl4]2− exchanged Cu/Al LDH, and surprisingly, the yield obtained wasCatalysts significantly2019, 9, 302 lower, 35% (Table 1, entry 8). 6 of 12

Table 1. Survey of reaction condition. Table 1. Survey of reaction condition.

O I O O Cu (%), Pd (%) B + O B B O N Base, solvent 2 O O O N 80oC 2 1 2 3

Entry Catalyst System Cu (mol%) Pd (mol%) Yield (%) 1 of 3 Entry Catalyst System Cu (mol%) Pd (mol%) Yield (%) 1 of 3 1 LDH 30 - 29% 1 2LDH Malachite 30 ‐ 30 -29% <5% 2 3Malachite Na2PdCl 4 30 ‐ - 2<5% <5% 3 4Na2PdCl PdNPs-CD4 ‐ -2 2<5% <5% 4 5PdNPs PdNPs-CD‐CD ‐ -2 2<5% <5% 6 Na PdCl /CuSO 30 2 <5% 5 PdNPs2 ‐CD4 ‐ 4 2 <5% 7 Na2PdCl4/LDH 30 2 98% 2 8 Na2PdCl4/CuSO4/LDH 30 2 77% 3 9 Na2PdCl4/LDH 30 2 35% 10 Na2PdCl4/LDH 15 2 54% 11 Na2PdCl4/LDH 7.5 2 42% 12 Na2PdCl4/LDH 3.75 2 26% 13 Na2PdCl4/LDH 30 1 46% 14 Na2PdCl4/LDH 30 0.5 42% 15 Na2PdCl4/LDH 30 0.05 23% 4 16 Na2PdCl4/LDH 30 2 <10% 5 17 Na2PdCl4/LDH 30 2 <10% 6 18 Na2PdCl4/LDH 30 2 <5%

1 2 3 Determined by gas chromatography–mass spectrometry (GC-MS); Use of Mg/Al LDH, CuSO4 and Na2PdCl4; 4 5 6 LDH intercalated with Na2PdCl4; solvent = THF; solvent = dioxane; Addition of Cs2CO3.

In order to see the effect of copper in the reaction, we have tested different copper loadings (Table1, entries 10–12). According to the results, a relatively high loading of copper has shown to be the most adequate for a high conversion (Table1, entry 7). Similarly, to verify the influence of the Pd loading it was varied from 2 to 0.05% under the same conditions (Table1, entries 13–15). In this case, 2 mol% Pd was necessary to keep an acceptable turnover. Analogously to Cu%, it was observed a direct relationship between the conversion rate and the Pd%. With the aim of evaluating the effect of noncoordinating solvents, THF and dioxane (Table1, entries 16 and 17) were also tested under the conditions described in Table1, entry 3. Surprisingly, no appreciable yield of the product was observed in both cases. Additionally, the use of base hampered the reaction (Table1, entry 18). Since the above results demonstrated that the catalytic system based on Cu/Al LDH and Pd(II) can be efficiently used for the borylation of an aryl iodide under ligand-free conditions, we carried out preliminary reactions with some aryl halides in order to examine its applicability. In this case, we have tested the influence of electron-withdrawing/donating groups substituted in the aromatic core. By considering their comparatively low-cost and availability, we have mainly focused on the evaluation of the reactivity of aryl bromides. In general, it was possible to note an influence of the electron-withdrawing/ donating capabilities of the substitutional groups. Remarkably, it was evident that the strongly electron-donating amine group did not favor the reaction in both cases (Table2, entries 1 and 5). In general, the absence of a substituent led to small yields. Catalysts 2019, 9, x FOR PEER REVIEW 6 of 12 Catalysts 2019,, 9,, x FOR PEER REVIEW 6 of 12 CatalystsCatalysts 20192019,, 99,, xx FORFOR PEERPEER REVIEWREVIEW 66 ofof 1212 Catalysts 2019, 9, x FOR PEER REVIEW 6 of 12 2 4 4 6 Na2PdCl4/CuSO/CuSO4 30 2 <5% 66 NaNa22PdClPdCl44/CuSO/CuSO44 3030 22 <5%<5% 6 Na22PdCl44/CuSO4 30 2 <5% 76 NaNa2PdCl2PdCl4/CuSO4/LDH/LDH 4 30 2 98%<5% 77 NaNa22PdClPdCl44/LDH/LDH 3030 22 98%98% 7 2 Na2PdCl4 4/LDH4 2 30 2 98% 87 Na2PdClNa2PdCl4/CuSO/CuSO4/LDH4/LDH/LDH 22 30 2 77%98% 88 NaNa22PdClPdCl44/CuSO/CuSO44/LDH/LDH 22 3030 22 77%77% 8 Na2PdCl2 4/CuSO4 4/LDH3 2 30 2 77% 98 Na2NaPdCl2PdCl4/CuSO4/LDH/LDH4/LDH 33 30 2 35%77% 99 NaNa22PdClPdCl44/LDH/LDH 33 3030 22 35%35% 9 Na22PdCl44/LDH 3 30 2 35% 109 NaNa2PdCl2PdCl44/LDH/LDH/LDH 1530 2 54%35% 1010 NaNa22PdClPdCl44/LDH/LDH 1515 22 54%54% 10 Na22PdCl44/LDH 15 2 54% 1110 Na2PdCl4/LDH/LDH 7.515 2 42%54% 1111 NaNa22PdClPdCl44/LDH/LDH 7.57.5 22 42%42% 11 Na22PdCl44/LDH 7.5 2 42% 1211 Na2PdCl4/LDH/LDH 3.757.5 2 26%42% 1212 NaNa22PdClPdCl44/LDH/LDH 3.753.75 22 26%26% 12 Na22PdCl44/LDH 3.75 2 26% 1312 Na2PdCl4/LDH/LDH 3.7530 12 46%26% 1313 NaNa22PdClPdCl44/LDH/LDH 3030 11 46%46% 13 Na22PdCl44/LDH 30 1 46% 1413 Na2PdCl4/LDH/LDH 30 0.51 42%46% 1414 NaNa22PdClPdCl44/LDH/LDH 3030 0.50.5 42%42% 14 Na22PdCl44/LDH 30 0.5 42% 1514 Na2PdCl4/LDH/LDH 30 0.050.5 23%42% 1515 NaNa22PdClPdCl44/LDH/LDH 3030 0.050.05 23%23% 15 Na22PdCl44/LDH4 30 0.05 23% 1615 NaNa2PdCl2PdCl4/LDH4/LDH/LDH 4 4 30 0.052 <10%23% 1616 NaNa22PdClPdCl44/LDH/LDH 44 3030 22 <10%<10% 16 Na22PdCl44/LDH 54 30 2 <10% 1716 Na2PdCl4/LDH/LDH 55 30 2 <10% 1717 NaNa22PdClPdCl44/LDH/LDH 55 3030 22 <10%<10% 17 Na22PdCl44/LDH 65 30 2 <10% 1817 Na2PdCl4/LDH/LDH 66 30 2 <10%<5% 1818 NaNa22PdClPdCl44/LDH/LDH 66 3030 22 <5%<5% 1 18 Na2PdCl4/LDH 6 30 22 <5% 1 Determined by gas chromatography–mass2 4 spectrometry (GC‐MS); 2 Use of Mg/Al LDH, CuSO4 and 1 Determined18 by gasNa chromatography–massPdCl /LDH spectrometry30 (GC‐MS); 22 Use of Mg/Al LDH,<5% CuSO 4 and 1 Determined by gas chromatography–mass spectrometry (GC‐MS); 2 Use of Mg/Al LDH, CuSO44 and 1 Determined3 by gas chromatography–mass spectrometry4 (GC5 ‐MS); 2 Use of Mg/Al6 LDH, CuSO 4 and Na1 Determined2PdCl4; 3 LDH by intercalatedgas chromatography–mass with Na2PdCl4; spectrometry4 solvent = THF; (GC 5 solvent‐MS); 2 =Use dioxane; of Mg/Al 6 Addition LDH, CuSO of Cs2 COand3. Na Determined2PdCl4; 3 LDH by gasintercalated chromatography–mass with Na2PdCl4 ;spectrometry 4 solvent = THF; (GC 5 solvent‐MS); Use= dioxane; of Mg/Al 6 Addition LDH, CuSO of Cs42 COand3 . Na22PdCl44; 3 LDH intercalated with Na22PdCl44; 4 solvent = THF; 5 solvent = dioxane; 6 Addition of Cs22CO33. NaNa2PdClPdCl4;; 3 LDHLDH intercalatedintercalated withwith NaNa2PdClPdCl4;; 4 solventsolvent == THF;THF; 5 solventsolvent == dioxane;dioxane; 6 AdditionAddition ofof CsCs2COCO3.. Na2PdCl4; 3 LDH intercalated with Na2PdCl4; 4 solvent = THF; 5 solvent = dioxane; 6 Addition of Cs2CO3. In order to see the effect of copper in the reaction, we have tested different copper loadings InIn orderorder tototo seesee thethethe effecteffect ofof coppercopper ininin thethethe reaction,reaction, wewe havehave testedtestedtested differentdifferent coppercopper loadingsloadingsloadings (TableIn 1, order entries to 10–12).see the According effect of copper to the results,in the reaction,a relatively we high have loading tested ofdifferent copper copperhas shown loadings to be (Table(Table 1,1, entriesentries 10–12).10–12). AccordingAccording tototo thethethe results,results, aa relativelyrelatively highhigh loadingloadingloading ofof coppercopper hashas shownshown tototo bebe the(Table most 1, adequateentries 10–12). for a highAccording conversion to the (Table results, 1, a entry relatively 7). Similarly, high loading to verify of copper the influence has shown of the to Pdbe thethethe mostmost adequateadequate forfor aa highhigh conversionconversion (Table(Table 1,1, entryentry 7).7). Similarly,Similarly, tototo verifyverify thethethe influenceinfluenceinfluence ofof thethethe PdPd loadingthe most it adequate was varied for from a high 2 toconversion 0.05% under (Table the 1,same entry conditions 7). Similarly, (Table to verify1, entries the 13–15).influence In thisof the case, Pd loadingloadingloading ititit waswas variedvaried fromfrom 22 tototo 0.05%0.05% underunder thethethe samesame conditionsconditions (Table(Table 1,1, entriesentries 13–15).13–15). InIn thisthisthis case,case, 2loading mol% itPd was was varied necessary from to2 to keep 0.05% an underacceptable the same turnover. conditions Analogously (Table 1, toentries Cu%, 13–15). it was Inobserved this case, a 22 mol%mol% PdPd waswas necessarynecessary tototo keepkeep anan acceptableacceptable turnover.turnover.turnover. AnalogouslyAnalogously tototo Cu%,Cu%, ititit waswas observedobserved aa direct2 mol% relationship Pd was necessary between to the keep conversion an acceptable rate and turnover. the Pd%. Analogously With the aim to of Cu%, evaluating it was theobserved effect of a directdirect relationshiprelationship betweenbetween thethethe conversionconversion raterate andand thethethe Pd%.Pd%. WithWith thethethe aimaim ofof evaluatingevaluating thethethe effecteffect ofof noncoordinatingdirect relationship solvents, between THF the conversionand dioxane rate (Table and the1, entries Pd%. With16 and the 17) aim were of evaluating also tested the under effect the of noncoordinatingnoncoordinating solvents,solvents, THFTHF andand dioxanedioxane (Table(Table 1,1, entriesentries 1616 andand 17)17) werewere alsoalso testedtestedtested underunder thethethe conditionsnoncoordinating described solvents, in Table THF 1,and entry dioxane 3. Surprisingly, (Table 1, entries no appreciable 16 and 17) wereyield alsoof the tested product under was the conditionsconditions describeddescribed ininin TableTable 1,1, entryentry 3.3. Surprisingly,Surprisingly, nono appreciableappreciable yieldyield ofof thethethe productproduct waswas observedconditions in described both cases. in Additionally, Table 1, entry the 3.use Surprisingly, of base hampered no appreciable the reaction yield (Table of 1,the entry product 18). was observedobserved ininin bothboth cases.cases. Additionally,Additionally, thethethe useuse ofof basebase hamperedhampered thethethe reactionreaction (Table(Table 1,1, entryentry 18).18). observedSince in the both above cases. results Additionally, demonstrated the use that of thebase catalytic hampered system the reactionbased on (Table Cu/Al 1, LDH entry and 18). Pd(II) SinceSince thethethe aboveabove resultsresults demonstrateddemonstrated thatthatthat thethethe catalyticcatalytic systemsystem basedbased onon Cu/AlCu/Al LDHLDH andand Pd(II)Pd(II) can beSince efficiently the above used results for the demonstrated borylation of that an arylthe catalytic iodide under system ligand based‐free on Cu/Alconditions, LDH weand carried Pd(II) cancan bebe efficientlyefficiently usedused forfor thethethe borylationborylation ofof anan arylaryl iodideiodideiodide underunder ligandligandligand‐‐freefree conditions,conditions, wewe carriedcarried outcan preliminarybe efficiently reactions used for with the borylationsome aryl halides of an aryl in order iodide to underexamine ligand its applicability.‐free conditions, In this we case, carried we outout preliminarypreliminary reactionsreactions withwith somesome arylaryl halideshalides ininin orderorder tototo examineexamine itsitsits applicability.applicability. InIn thisthisthis case,case, wewe haveout preliminary tested the influence reactions ofwith electron some‐ arylwithdrawing/donating halides in order to examinegroups substituted its applicability. in the In aromatic this case, core. we havehave testedtestedtested thethethe influenceinfluenceinfluence ofof electronelectron‐‐withdrawing/donatingwithdrawing/donating groupsgroups substitutedsubstituted ininin thethethe aromaticaromatic core.core. Byhave considering tested the influencetheir comparatively of electron‐withdrawing/donating low‐cost and availability, groups we substituted have mainly in the focused aromatic on core. the ByBy consideringconsidering theirtheirtheir comparativelycomparatively lowlowlow‐‐costcost andand availability,availability, wewe havehave mainlymainly focusedfocused onon thethethe evaluationBy considering of the theirreactivity comparatively of aryl bromides. low‐cost and availability, we have mainly focused on the evaluationevaluation ofof thethethe reactivityreactivity ofof arylaryl bromides.bromides. evaluationIn general, of the it reactivitywas possible of aryl to note bromides. an influence of the electron‐withdrawing/ donating capabilities InIn general,general, ititit waswas possiblepossible tototo notenote anan influenceinfluenceinfluence ofof thethethe electronelectron‐‐withdrawing/withdrawing/ donatingdonating capabilitiescapabilities of theIn substitutional general, it was groups. possible Remarkably, to note an influence it was evident of the electron that the‐withdrawing/ strongly electron donating‐donating capabilities amine ofof thethethe substitutionalsubstitutional groups.groups. Remarkably,Remarkably, ititit waswas evidentevident thatthatthat thethethe stronglystrongly electronelectron‐‐donatingdonating amineamine groupof the substitutionaldid not favor thegroups. reaction Remarkably, in both cases it was (Table evident 2, entries that the 1 and strongly 5). In general,electron ‐thedonating absence amine of a groupgroup diddid notnot favorfavor thethethe reactionreaction ininin bothboth casescases (Table(Table 2,2, entriesentries 11 andand 5).5). InIn general,general, thethethe absenceabsence ofof aa substituentgroup did not led favorto small the yields.reaction in both cases (Table 2, entries 1 and 5). In general, the absence of a Catalystssubstituentsubstituent2019, 9, 302 ledledled tototo smallsmall yields.yields. 7 of 12 substituent led to small yields. 1 Table 2. Preliminary scope for the borylation reaction catalyzed by Cu/Al LDH and Na2PdCl4 1. Table 2. Preliminary scope for the borylation reaction catalyzed by Cu/Al LDH and Na2PdCl4 1. Table 2. Preliminary scope for the borylation reaction catalyzed by Cu/Al LDH and Na22PdCl44 1 . TableTable 2.2. PreliminaryPreliminary scopescope forfor thethe borylationborylation reactionreaction catalyzedcatalyzed byby Cu/AlCu/Al LDHLDH andand NaNa2PdClPdCl1 4 1.. TableTable 2. Preliminary 2. Preliminary scope scope for the for borylation the borylation reaction reaction catalyzed catalyzed by Cu/Al by Cu/Al LDH LDH and and Na2 PdClNa2PdCl4 . 4 1. Entry Aryl Halide Product Yield (%) EntryEntry ArylAryl HalideHalide ProductProduct YieldYield (%)(%) EntryEntry Aryl Aryl Halide Product Product YieldYield (%) (%) O O OB I OB I OB O I B O II B O 1 H N B O <10 1 H N I H2 N O <10 1 H2 N H22N <10 11 H22N H2N <10<10 1 HH2NN H2N <10 2 H2N H2N 4 44 4 O O OBO Br OB O Br OB O BBrr BB O 22 Br B OO <10<10 22 Br O <10<10 2 <10 5 55 Catalysts 2019, 9, x FOR PEER REVIEW 5 7 of 12 Catalysts 2019,, 9,, x FOR PEER REVIEW 7 of 12 Catalysts 2019, 9, x FOR PEER REVIEW Br O 7 of 12 Catalysts 2019, 9, x FOR PEER REVIEW Br O 7 of 12 Catalysts 20192019,, 99,, xx FOR PEER REVIEW BrBr OB 77 ofof 1212 O Br OB O Catalysts 2019, 9, x FOR 3PEER REVIEW O Br 6 BO O 55 7 of 12 33 OO O 6 B O 55 55 3 O O 6 B O 55 3 O OO 6 O 55 3 O 6 55 O 6 6 O 6 O 6 OB Br O O Br BO Br OB O 4 Br H CO OB O 98 4 H CO Br 3 BO O 98 4 3 Br H3CO B O 98 4 H3CO Br 3 O 98 4 3 Br H3CO B 98 H3CO H3CO O 4 H3CO H CO 98 44 H CO H3 CO 7 98 98 4 H3 CO 3 7 98 3 H3CO 7 H3CO 7 77 7 O 7 O OB Br OB O Br BO Br OB O Br OB 5 Br H N O <10 5 H2N 2 BO O <10 5 Br H2N B <10 H2N H2N O 5 H2N Br B O <10 55 H N Br H2N <10<10 5 H2 N H2N O <10 5 2 H2N 4 <10 H2N H2N 5 H2N 4 <10 H N H2N 2 44 4 O 4 BO Br BO Br HO BO Br Br HO BO 6 Br Br HO BO 30 66 Br Br HO BO 30 30 6 Br Br HO BO 30 6 Br Br HO 8 BO 30 Br Br HO O 6 Br HO 8 O 30 6 Br 8 30 88 8 O O Br O B O O B O BBrr O B O Br O B O 77 Br O B O 45 45 7 Br O B O 45 7 Br O B O 45 7 Br B 45 77 4545 7 9 45 7 9 45 9 1 Determined by GC-MS. 99 1 Determined by GC9‐MS. 11 Determined by GC‐9MS. 1 Determined by GC9‐MS. Encouraged by the preliminary results,1 Determined we next investigated by GC‐MS. whether this catalyst could have 1 Determined by GC‐MS. 1 Determined by GC‐‐MS. recyclingEncouraged potential. In by such the case,preliminary it could results, shed1 Determined a we light next onby GC theinvestigated‐MS. behavior whether of Cu/Al this LDH catalyst as a reservoir could have Encouraged by thethe preliminary results, we next investigatedinvestigated whether thisthis catalyst could have or asrecycling realEncouragedEncouraged catalytically potential. byby active In thethe such preliminarypreliminary species. case, it However, could results,results, shed attempts wewe a light nextnext on investigated toinvestigated the recover behavior the whetherwhether material of Cu/Al thisthis after LDH catalystcatalyst reaction as a reservoircouldcould work havehave or recyclingEncouraged potential. by InIn thethe such preliminary case, itit could results,results, shed we a lightlight next on investigatedinvestigated thethe behavior whether of Cu/Al thisthis LDH catalyst as a reservoircould have or up failed.recyclingasrecycling realEncouraged catalytically potential.potential. by InactiveIn the suchsuch preliminary species. case,case, itit However,couldcould results, shedshed attemptswe aa lightlight next on on investigatedto the therecover behaviorbehavior the whether material ofof Cu/AlCu/Al this after LDHLDH catalyst reaction asas aa reservoirreservoircould work have up oror recyclingasrecycling real catalytically potential. activeInIn suchsuch species. case, itit However,could shedshed attempts a lightlight on toto the the recover behavior thethe material of Cu/Al after LDH reaction as a reservoirreservoir work up or asrecyclingfailed.as realreal catalyticallycatalytically potential. activeInactive such species.species. case, it However,However,could shed attemptsattempts a light on toto the recoverrecover behavior thethe material materialof Cu/Al afterafter LDH reactionreaction as a reservoir workwork up upor 3. Discussionasfailed.failed. realreal catalytically active species.species. However, attempts toto recoverrecover thethe material after reactionreaction work up failed.asfailed. real catalytically active species. However, attempts to recover the material after reaction work up failed.failed. 3.failed.Malachite Discussion is a common second phase present in Cu/Al LDH synthetic samples [20–26], and it 3. Discussion is known3.3. DiscussionDiscussionMalachite to affect theis a general common properties second phase of the present LDH, such in Cu/Al as its LDH catalytic synthetic properties samples [23 –[20–26],25]. In mostand it is 3. DiscussionMalachite isis a common second phase present inin Cu/Al LDH synthetic samples [20–26],[20–26], and itit isis cases,known itMalachite arisesMalachite to affect from isis the aa commoncommon needgeneral to usesecondsecondproperties sodium phasephase of carbonate presentthepresent LDH, inin as such Cu/AlCu/Al a precipitation as LDHLDH its catalytic syntheticsynthetic co-agent, properties samplessamples otherwise [20–26],[20–26],[23–25]. LDH andandIn ismost itit isis knownMalachite toto affect isis thethe a common general secondpropertiessecond phase of thepresentthe LDH, inin such Cu/Al as LDH itsits catalytic syntheticsynthetic properties samplessamples [20–26],[23–25].[20–26],[23–25]. andInIn most itit isis notknowncases,known formedMalachite it to to asarises affectaffect the majority fromis thethe a common thegeneralgeneral phase, need secondpropertiesproperties to as use observed phasesodium ofof inthepresentthe carbonate Figure LDH,LDH, in2 a. suchsuchCu/Al Theas aasas way precipitationLDH itsits thecatalyticcatalytic synthetic unit cell copropertiesproperties ‐samples dimensionsagent, otherwise [20–26],[23–25].[23–25]. obtained andIn InLDH mostmost it is knowncases, itit to toarises affect fromfrom thethe thethegeneral need properties toto use sodium of thethe carbonate LDH, suchsuch as aas precipitation itsits catalytic coproperties‐‐agent, otherwise [23–25].[23–25]. In InLDH most isis forcases,known thisnotcases, formed phase itit to arisesarises affect (Table as the fromfrom the S1,majority thethegeneral supporting needneed phase, properties toto useuse material) as sodiumobservedsodium of the evidenced carbonatecarbonate inLDH, Figure such an as as2a. expanded aaas The precipitationprecipitation its way catalytic network the unit cocoproperties‐ ‐cellagent,agent, in comparison dimensions otherwiseotherwise [23–25]. toobtained In LDHLDH the most isis cases,not formedformed itit arises as the thefromfrom majority thethe need phase, toto use as observedsodiumsodium carbonate inin Figure as 2a. a The precipitation way thethe unit co‐ ‐ cellagent, dimensions otherwise obtained LDH isis carbonatenotcases,fornot thisformedformed it containing phasearises asas thethe(Tablefrom majoritymajority LDH the S1, need phases. supporting phase,phase, to use This asas observedsodiumobservedmaterial) can be understoodcarbonate ininevidenced FigureFigure as 2a.2a. in ana TheThe termsprecipitation expanded wayway of thethe attraction network unitunit co‐ cellcellagent, electrostatic dimensionsdimensionsin comparisonotherwise forces obtainedobtained LDH to the is notforfor thisthisformedformed phase as the(Tablethe(Table majority S1, supporting phase, as observedmaterial) ininevidenced Figure 2a. an The expanded way thethe network unit cell dimensionsinin comparison obtained toto thethe actingfornotcarbonatefor betweenthisthisformed phasephase containing as layer the(Table(Table majority and S1, S1,LDH interlayer supportingsupporting phase, phases. partsas This observedmaterial)material) of can the be material inevidencedevidenced understoodFigure that 2a. anan The permit expandedinexpanded termsway to the of pack network network unitattraction more cell dimensionsinin efficiently electrostaticcomparisoncomparison whenobtained forcestoto thethe forcarbonatefor2− thisthis phase containing (Table(Table− S1, LDH supportingsupporting phases. This material) can be evidenced understood an inexpandedin termsterms of network attraction inin electrostaticcomparison forcesforcestoto thethe COcarbonate3foractingcarbonate thisinstead between phase containingcontaining of (Table NO layer3 is S1, LDHandLDH used supporting interlayer phases.phases. as the intercalated ThisThis material)parts cancan of bebethe evidenced ion.understoodunderstood material an that inexpandedin termspermitterms ofof tonetwork attractionattraction pack more in electrostaticelectrostaticcomparison efficiently forcesforcestowhen the carbonateacting between containing layerlayer andLDH interlayerinterlayer phases. This parts can of bethethe understood material thatthat in termspermit of toto attraction pack more electrostatic efficiently forceswhen actingcarbonate2‐ between containing layer‐ andLDH interlayer phases. This parts can of bethe understood material that in permitterms of to attraction pack more electrostatic efficiently forceswhen carbonateCOacting32‐ instead between containing of layerNO3‐ isLDHand used interlayer phases. as the Thisintercalated parts can of bethe understoodion. material that in termspermit of to attraction pack more electrostatic efficiently forceswhen actingCO332‐ insteadinstead between of layerNO33‐ isandis used interlayer as thethe intercalatedintercalated parts of the ion.ion. material that permit to pack more efficiently when acting32‐ between layer3‐ and interlayer parts of the material that permit to pack more efficiently when COactingCO32Some‐ insteadinstead between authors ofof layerNONO in3‐ is andisthe usedused interlayerliterature asas thethe intercalated intercalated haveparts triedof the to ion.ion. material eliminate that the permit malachite to pack impurity more efficientlyby a number when of 32‐Some authors in3‐ the literature have tried to eliminate the malachite impurity by a number of CO 32‐Some insteadinstead authors of NO in3‐ is isthe used literature as thethe intercalated intercalatedhave tried toion.ion. eliminate the malachite impurity by a number of COdifferent32‐SomeSome instead approaches. authorsauthors of NO inin3‐ is thethe used literatureliterature as the intercalated havehave triedtried totoion. eliminateeliminate thethe malachitemalachite impurityimpurity byby aa numbernumber ofof differentSome approaches. authors inin thethe literatureliterature have triedtried toto eliminate thethe malachite impurityimpurity by a number of differentdifferentSomeMuñoz approaches.approaches. authors et al. [23] in thesought literature for pure have Cu/Al tried LDH to eliminate in order tothe obtain malachite its calcined impurity‐oxide by derivativea number ofto differentMuñoz approaches. et al. [23][23] sought forfor pure Cu/Al LDH inin order toto obtain itsits calcined‐‐oxide derivative toto differentcatalyzeMuñozMuñoz theapproaches. etetreduction al.al. [23][23] soughtsought of NO for forand purepure CO Cu/AlCu/Algases. LDH LDHThrough inin orderorder coprecipitation toto obtainobtain itsits method calcinedcalcined synthesis‐‐oxideoxide derivativederivative they were toto catalyzeMuñoz thethe etreduction al. [23][23] sought sought of NO for forand pure CO Cu/Al gases. LDH Through inin order coprecipitation toto obtain itsits method calcined synthesis‐‐oxide derivative theythey were toto catalyzeablecatalyze Muñozto verifythethe etreductionreduction al.that [23] precursors sought ofof NONO for andand solutions pure COCO Cu/Al gases.gases. with LDH ThroughThrough lower in order coprecipitationconcentrationscoprecipitation to obtain its methodprevented methodcalcined synthesissynthesis‐oxide the formationderivative theythey werewere toof catalyzeable toto verifythethe reductionreduction thatthat precursors of NO and solutions CO gases. with Through lowerlower concentrationscoprecipitation preventedmethod synthesissynthesis thethe formationformation theythey were of ablecatalyzemalachite,able toto verifyverifythe and reduction thatthat theprecursorsprecursors ofoxide NO derivedand solutionssolutions CO from gases. withwith malachite Through lowerlower‐ free concentrationscoprecipitationconcentrations LDH showed preventedmethodprevented better catalyticsynthesis thethe formationformation results they werethan ofof ablemalachite, toto verify and thatthat thetheprecursors oxide derived solutionssolutions fromfrom with malachite lowerlower‐‐ free freeconcentrations LDH showed prevented better catalytic thethe formationformation results thanthan of malachite,ablethemalachite, derived to verify andand from thatthat impure thetheprecursors oxideoxide LDH. derivedderived solutionsGao et fromfrom al. with[24] malachitemalachite synthetizedlower‐‐free freeconcentrations LDHLDH Cu/Zn/Al/Zr showedshowed prevented betterbetterLDH incatalyticcatalytic orderthe formation toresultsresults obtain thanthan itsof malachite,thethe derived and fromfrom thatthat impureimpure thethe oxide LDH. derived Gao et fromfrom al. [24][24] malachite synthetized‐‐freefree LDH Cu/Zn/Al/Zr showedshowed betterLDH inincatalytic order totoresultsresults obtain thanthan itsits themalachite,calcinedthe derivedderived oxide and fromfrom forthat impure impurethe the catalysis oxide LDH.LDH. derived ofGaoGao CO etet 2from hydrogenation,al.al. [24][24] malachite synthetizedsynthetized‐free and LDH Cu/Zn/Al/ZralsoCu/Zn/Al/Zr showedfound that betterLDHLDH catalysts inincatalytic orderorder with totoresults malachiteobtainobtain than itsits thecalcined derived oxide from forfor impure thethe catalysis LDH. ofGao CO et22 hydrogenation,al. [24] synthetized and Cu/Zn/Al/Zralso foundfound thatthat LDH catalysts in order with to malachiteobtain its the derived from impure LDH. Gao et2 al. [24] synthetized Cu/Zn/Al/Zr LDH in order to obtain its calcinedthepriorcalcined derived to theoxideoxide calcinationfrom forfor impure thethe catalysiscatalysis presented LDH. ofofGao COworseCO et2 hydrogenation,hydrogenation,al. catalytic [24] synthetized activity andand than alsoCu/Zn/Al/Zralso the foundfound ones thatthat withoutLDH catalystscatalysts in theorder withcontamination.with to malachitemalachiteobtain its prior to the calcination presented worse2 catalytic activity than the ones without the contamination. calcinedprior to theoxide calcination forfor thethe catalysis presented of COworse2 hydrogenation, catalytic activity and than also the foundfound ones thatthat without catalysts the withcontamination. malachite priorcalcinedBothprior Muñoztoto thetheoxide calcinationcalcination and for Gao the agreecatalysis presentedpresented that of higher worseCOworse2 hydrogenation, ratios catalyticcatalytic of Cu/Al activityactivity andinduce thanthan also thethethe found formationonesones that withoutwithout catalysts of malachite. thethe contamination.withcontamination. malachite Ichikawa priorBoth Muñoztoto thethe calcination and Gao agree presented thatthat higher worse ratios catalytic of Cu/Al activity induceinduce thanthan thethethethe formationformationones without of malachite. thethe contamination. IchikawaIchikawa BothprioretBoth al. MuñozMuñoz[25]to the tried calcination andand a differentGaoGao agreeagree presented way thatthat to higherhigher worseobtain ratiosratios catalyticnoncontaminated ofof Cu/AlCu/Al activity induceinduce than Cu/Al thethethe LDH: formationformationones withoutthey ofofused malachite.malachite. the a contamination.coprecipitation IchikawaIchikawa Bothet al. Muñoz[25][25] triedtried and a differentGao agree way thatthat toto higher obtain ratiosratios noncontaminated of Cu/Al induceinduce Cu/Al thethe LDH: formationformation theythey ofused malachite. a coprecipitation IchikawaIchikawa etBothmethodet al.al. Muñoz[25][25] followed triedtried and aa different differentGaoby an agree aging wayway that process toto higher obtainobtain at 90ratios noncontaminatednoncontaminated °C underof Cu/Al air bubblinginduce Cu/AlCu/Al the for LDH:LDH:formation 1 h. Theytheythey ofusedstatedused malachite. aa that coprecipitationcoprecipitation this Ichikawa process etmethod al. [25] followedfollowed tried a different by an aging way process to obtain at 90 noncontaminated °C under air bubbling Cu/Al forfor LDH: 1 h. Theythey statedused a thatthat coprecipitation thisthis process methodet al. [25] followed tried a differentby an aging way process to obtain at 90 noncontaminated °C under air bubbling Cu/Al for LDH: 1 h. They 2they− statedused a that coprecipitation this process ethelpedmethod al. [25] to followed triedsmooth a different bythe an crystallization aging way process to obtain process at 90 noncontaminated °C removing under air thebubbling excess Cu/Al for of LDH: CO1 h.3 2Theythey− ions. usedstated They a that coprecipitationalso this found process that methodhelped toto followed smooth by thethe an crystallization aging process process at 90 °C removing under air thethebubbling excess for of CO1 h.3 3They2− ions.ions. stated They that also this foundfound process thatthat method followed by an aging process at 90 °C under air bubbling for 1 h.3 2They− stated that this process helpedmethodthehelped calcined toto followed smoothsmooth oxide by thethe derived an crystallizationcrystallization aging from process the processprocess atpure 90 °C Cu/Al removingremoving under LDH air thethebubbling was excessexcess a better for ofof CO1CO h. catalyst 3They2− ions.ions. stated TheytoThey the that alsoalso conversion this foundfound process thatthat of the calcined oxide derived from the pure Cu/Al LDH was a better catalyst32− to the conversion of helpedthe calcined toto smoothsmooth oxide thethe derived crystallization from the process pure Cu/Al removingremoving LDH thethe was excess a better of CO catalyst32− ions.ions. Theyto the also conversion foundfound thatthat of thehelpedacrylonitrile calcined to smooth oxideto acrylamide the derived crystallization fromthan the process purecontaminated Cu/Al removing LDH one. the was Recently,excess a better of COQu catalyst3 2−et ions. al. to[26]They the reported also conversion found a newthat of theacrylonitrilethe calcinedcalcined oxidetooxide acrylamide derivedderived fromthanfrom thethe contaminatedpurepure Cu/AlCu/Al LDHLDH one. waswas Recently, aa betterbetter Qu catalystcatalyst et al. [26]toto thethe reported conversionconversion a new ofof acrylonitrilethe calcined totooxide acrylamide derived thanfromthan thethethe contaminatedpure Cu/Al LDH one. was Recently, a better Qu catalyst et al. [26][26]to the reported conversion a new of the acrylonitrile calcined oxideto acrylamide derived fromthan the purecontaminated Cu/Al LDH one. was Recently, a better Qu catalyst et al. to[26] the reported conversion a new of acrylonitrile toto acrylamide thanthan thethe contaminated one. Recently, Qu et al. [26][26] reportedreported a new acrylonitrile to acrylamide than the contaminated one. Recently, Qu et al. [26] reported a new

Catalysts 2019, 9, 302 8 of 12

Some authors in the literature have tried to eliminate the malachite impurity by a number of different approaches. Muñoz et al. [23] sought for pure Cu/Al LDH in order to obtain its calcined-oxide derivative to catalyze the reduction of NO and CO gases. Through coprecipitation method synthesis they were able to verify that precursors solutions with lower concentrations prevented the formation of malachite, and that the oxide derived from malachite-free LDH showed better catalytic results than the derived from impure LDH. Gao et al. [24] synthetized Cu/Zn/Al/Zr LDH in order to obtain its calcined oxide for the catalysis of CO2 hydrogenation, and also found that catalysts with malachite prior to the calcination presented worse catalytic activity than the ones without the contamination. Both Muñoz and Gao agree that higher ratios of Cu/Al induce the formation of malachite. Ichikawa et al. [25] tried a different way to obtain noncontaminated Cu/Al LDH: they used a coprecipitation method followed by an aging process at 90 ◦C under air bubbling for 1 h. They stated that this process helped to smooth 2− the crystallization process removing the excess of CO3 ions. They also found that the calcined oxide derived from the pure Cu/Al LDH was a better catalyst to the conversion of acrylonitrile to acrylamide than the contaminated one. Recently, Qu et al. [26] reported a new mechanochemical synthesis method for Cu/Al LDH, in which they dry milled Cu2(OH)2CO3 and Al(OH)3 at a planetary ball mill for 2 h at 600 rpm, producing an amorphous solid mixture that was treated in aqueous medium at room temperature under magnetic stirring for 4 h, producing a pure Cu/Al LDH. Another important feature is the presence of nitratine (NaNO3) in the phase mixture composition after LDH synthesis. Firstly, this phase arises from the combination of sodium of NaOH solution and nitrate from salt precursors of Cu2+ and Al3+. However, considering sodium nitrate is soluble in aqueous medium, it is not clear how this phase coprecipitates with LDH. Figure4 gives a hint: the centrifugation process leads to 5-fold increase of nitratine% in the phase mixture composition. In addition, Figure5 points to a decrease by half of this phase percentage guaranteed by washing with EtOH/Acetone. Therefore, the combined use of filtration and washing in the postsynthesis work-up of LDH is beneficial for this catalyst. The catalytic conditions studied for the borylation model reaction were initiated with an activated aryl iodide since electron-withdrawing groups are known for the accelerated effect on the reaction rate [7]. Under the basic conditions of the classical Pd cycle, it is assumed that the higher the Ar-Pd(II)-X electrophilicity, the faster the transmetallation with bisorganodiboron. In fact, the results pointed to a high catalytic conversion by using 4-iodonitrobenzene as an electrophile. To evidence the clean and selective conditions for the borylation reaction, the crude 1H NMR spectrum of 3 is presented in the Supporting Information. A relatively high copper loading was, however, necessary to increase the substrate conversion. As pointed out, this fact has already been observed by Ratnyom [12] and other groups [13] but involving a typically homogeneous catalytic system based on Cu or Pd/Cu combined with phosphines. Regarding the usual organometallic mechanism, it is interesting to note that the LDH surface is possibly responsible for the presence of basic species involved in the preactivation step. The addition of base, however, was detrimental to the reaction, suggesting a partial decomposition of the LDH structure. Even though the cooperative catalysis of Pd and Cu was already reported in some recent works, the ligand-free condition has been scarcely explored mostly because of the difficult electronic tuning towards the transmetallation step even though the soft coordination of acetonitrile cannot be ruled out. However, the surprising fact here is related to the superior activity of a heterogeneous layered Cu matrix, which allowed high substrate conversion and product selectivity in the reaction model. In detriment, common copper salts, such as the basic copper carbonate (malachite), were ineffective under the same conditions, indicating that the chemical environmental around copper is decisive to the reaction outcome even in the presence of palladium. This fact could be reinforced when testing Mg/Al LDH in the presence of CuSO4 and Na2PdCl4 that resulted in an inferior product yield compared to the same catalytic conditions by using the Cu/Al matrix. Catalysts 2019, 9, 302 9 of 12

In addition, the preliminary scope of the method showed an unclear electronic effect of substituents: apparently, the reaction is favored by both electron-donating and -withdrawing groups but, intriguingly, it was not the case for the amine substituent. It is conceivable that a hybrid mechanism is operative with the moderate to low yields of α-naphtyl, 4-bromobenzyl and phenyl bromides arising from a predominant oxidative addition modulation. However, the low reactivity of bromobenzene was intriguing. We presume the occurrence of possible alternative pathways (e.g., Ullmann-type reaction and hydrodehalogenation) in minor extension but the solubility factor cannot be ruled out. Indeed, Catalysts 2019, 9, x FOR PEER REVIEW 9 of 12 the role of LDH matrix as a catalytic reservoir of active Cu species can be considered based on experimentsconsidered based with on coordinating experiments solvents with coordinating [27]. According solvents to the [27]. frustrated According catalyst to the recycling frustrated attempts, catalyst itrecycling is also possibleattempts, that it is acetonitrile also possible act that as aacetonitrile moderate act LDH as exfoliationa moderate agent.LDH exfoliation On the other agent. hand, On the effect of PdCl 2− intercalation in LDH seems to slow down the possible Pd(II) reduction. Lastly, the other hand, the4 effect of PdCl42− intercalation in LDH seems to slow down the possible Pd(II) (Bpin) seems to be involved in the reduction of Pd(II) species, as suggested by the solution darkening reduction.2 Lastly, (Bpin)2 seems to be involved in the reduction of Pd(II) species, as suggested by the accordingsolution darkening to visual inspection.according to visual inspection. Taken together,together, thesethese resultsresults suggestsuggest that a synergicsynergic effecteffect betweenbetween the Cu(II) and Pd(0) species can arise from a combination of factors related to the electronic effects on substrate along with the chemicalCatalysts environment 2019, 9, x FOR of PEER both REVIEW metals. 9 of 12 A schematic view containing some of these effectseffects isis shownshown inin SchemeScheme1 1.. Ar-X (Bpin)2 2- [PdCl4] Pd(0) Ar-X (Bpin)2 2- [PdCl4] Pd(0) OH Ar-Bpin

OH Ar-BpinOH Ar-Pd-Bpin Ar-Pd-X ArPdL OH OH OH Ar-Pd-Bpin Ar-Pd-X ArPdL OH MeCN OH 2- 2MeCN- [PdCl4] [PdCl4] CuL2 L-Cu-Bpin 2- 2- Partial LDH exfoliation [PdCl4] [PdCl4] CuL2 L-Cu-Bpin Partial LDH exfoliation (Bpin)2

Cu/Al LDH (Bpin)2 Cu/Al LDH Cu Cu

Scheme 1. Proposed mechanism for the Pd and Cu-catalyzed aryl borylation in the presence of SchemeScheme 1. Proposed 1. Proposed mechanism mechanism for for the the Pd Pd and and Cu-catalyzed CuLDH.‐catalyzed aryl aryl borylation borylation in the in the presence presence of LDH. of LDH. 4. Materials4. Materials and and Methods Methods 4. MaterialsAll theAll and reactants the Methods reactants and and solvents solvents in this in thiswork work were were commercially commercially acquired acquired and and used used without without previouspreviousAll the purification. reactants purification. and solvents in this work were commercially acquired and used without previousThe powderThepurification. powder X-ray X - diffractogramsray diffractograms were were recorded recorded by a by diffractometer a diffractometer Panalytical Panalytical X´Pert X´Pert PRO PRO MPD MPD (Malvern(TheMalvern powder Panalytical Panalytical X‐ray Ltd., diffractograms Ltd., Royston, Royston, United were United recorded Kingdom), Kingdom by a with )diffractometer, with generator generator Panalytical of of Cu Cu X-ray X-ray X´Pert ( λ(λ= = PRO 1.54181.5418 MPD Ǻ),), line 1 ◦ line(Malvern focusfocus Panalytical (1.8 kW), universal Ltd., Royston, Theta Theta-2Theta- United2Theta Kingdom goniometer), with with with generator 240 240 mm mm radius, radius, of Cu Xdivergence divergence‐ray (λ = 1.5418 slit slit fixed fixed Ǻ), line½°,2 , flat- flat-diffractedfocusdiffracted (1.8 kW), beam beamuniversal monochromator, monochromator, Theta‐2Theta and andgoniometer proportional proportional with detector 240detector mm Xe radius, Xe with with 40 divergence kV40 kV of tension of tension slit fixed and and 40 ½°, mA 40 flat mA of‐ of currentdiffractedcurrent in thebeam in X-ray the monochromator, X- tube.ray tube. The The samples samplesand wereproportional were analyzed analyzed detector self-supported self Xe-supported with in 40 aluminum kV in aluminumof tension sample sampleand holder 40 holdermA and of and usedcurrentused under in underthe the X‐ Bragg–Brentanoraythe tube.Bragg The–Brentano samples geometry; geometry were itanalyzed used; it used ranges self ranges‐supported between between 5 ◦in< aluminum 25θ° < 2θ 70 ◦<, with70 sample°, with 0.05 holder ◦0.05step° step and and 2.5used s2.5 perunder s step.per the step. Bragg–Brentano geometry; it used ranges between 5° < 2θ < 70°, with 0.05° step and 2.5 s Theper step.The calculation calculation based based on the on Rietveldthe Rietveld Refinement Refinement applied applied in this in work,this work, through through the programthe program TOPASTOPASThe academic calculation academic V5.0 based V5.0 (Coelho on (Coelho the Software, Rietveld Software, Refinement Brisbane, Brisbane, Australia), applied Australia in was this), was basedwork, based through on the on Fundamental thethe Fundamentalprogram ParametersTOPASParameters academic Approach, Approach, V5.0 based (Coelho on based the Software, instrumental on the Brisbane, instrumental parameters Australia parameters with), background was withbased correction.background on the Fundamental If necessary, correction. If theParameters followingnecessary, Approach, parameters the following based were parameters refined;on the unitinstrumental were cell refined dimensions, ; parametersunit cell sample dimensions with height background, displacement,sample height correction. zero-shift,displacement If , weightnecessary,zero fraction-shift the ,following weight (scaling), fraction parameters preferred (scaling) were orientation, ,refined; preferred atomic unit orientation cell species/substitutions, dimensions,, atomic sample species/substitutions height atomic displacement, coordinates,, atomic sitezero occupancies,‐coordinatesshift, weight, thermalsite fraction occupancies displacement (scaling),, thermal preferred parameters, displacement orientation, crystallite parameters size,atomic and, crystallite species/substitutions, lattice strain. size, and lattice atomic strain. coordinates,All sitethe organicoccupancies, products thermal were displacement characterized parameters, by 1H and 13 Ccrystallite NMR spectroscopy size, and lattice (Bruker strain. Analytics, Berlin,All the Germany)organic products. were characterized by 1H and 13C NMR spectroscopy (Bruker Analytics, Berlin, Germany). 4.1. Synthesis of the Cu/Al Layered Double Hydroxides 4.1. Synthesis of the Cu/Al Layered Double Hydroxides The Cu/Al layered double hydroxides (Cu/Al LDH) and Cu4Al2(OH)12CO3·4H2O, were −1 synthetized The Cu/Al us layereding a constant double pH hydroxides method: one (Cu/Al aqueous LDH) solution and of CuCu(NO4Al2(OH)3)2·3H12CO2O (0.2253∙4H2O, mol·L were) and −1 −1 synthetizedAl(NO3 )using3·9H2O a constant (0.075 mol·L pH method:) and other one aqueous of NaOH solution (0.50 mol·Lof Cu(NO) and,3)2∙3H alternatively,2O (0.225 mol Na∙L−21CO) and3 (0.15 −1 Al(NOmol·L3)3∙9H),2 Owere (0.075 added mol ∙(40L−1 ) mLand each) other simultaneously of NaOH (0.50 by mol continuous∙L−1) and, droppingalternatively, to 40 Na mL2CO of3 (0.15a NaOH mol∙solutionL−1), were (pH added = 8 or (40 10), mL under each) magnetic simultaneously stirring at by room continuous temperature. dropping The pH to was40 mL maintained of a NaOH during solutionthe process.(pH = 8 orA 10),blue under slurry magnetic was formed, stirring which at room was temperature. then filtrated The or pHcentrifuged was maintained and dried during at room temperature. The filtrated material was alternatively washed with ethanol:acetone 1:1 volume

mixture.

Catalysts 2019, 9, 302 10 of 12

All the organic products were characterized by 1H and 13C NMR spectroscopy (Bruker Analytics, Berlin, Germany).

4.1. Synthesis of the Cu/Al Layered Double Hydroxides

The Cu/Al layered double hydroxides (Cu/Al LDH) and Cu4Al2(OH)12CO3·4H2O, were synthetized using a constant pH method: one aqueous solution of Cu(NO3)2·3H2O −1 −1 −1 (0.225 mol·L ) and Al(NO3)3·9H2O (0.075 mol·L ) and other of NaOH (0.50 mol·L ) and, −1 alternatively, Na2CO3 (0.15 mol·L ), were added (40 mL each) simultaneously by continuous CatalystsCatalysts 2019 2019, 9, ,x 9 FOR, x FOR PEER PEER REVIEW REVIEW 10 of10 12of 12 dropping to 40 mL of a NaOH solution (pH = 8 or 10), under magnetic stirring at room temperature. theThethe process. process. pH was A A maintainedblue blue slurry slurry was during was formed, formed, the process. which which was A was blue then then slurry filtrated filtrated was or formed, orcentrifuged centrifuged which and was and dried then dried filtratedat atroom room or temperature.centrifugedtemperature. The and The filtrated dried filtrated at roommaterial material temperature. was was alternatively alternatively The filtrated washed washed material with with wasethanol:acetone ethanol:acetone alternatively 1:1 washed 1:1 volume volume with mixture.ethanol:acetonemixture. 1:1 volume mixture. 4.2. Synthesis of Boronic Esters Employing Palladium Nanoparticles 4.2.4.2. Synthesis Synthesis of Boronicof Boronic Esters Esters Employing Employing Palladium Palladium Nanoparticles Nanoparticles The synthesis of PdNPs followed method described by Senra et al. [19], Scheme2. At first, 1 mL of The synthesis of PdNPs followed method described by Senra et al. [19], scheme 2. At first, 1 mL The synthesis of PdNPs−1 followed method described by Senra et al. [19], scheme 2. At first, 1 mL a Na2PdCl4 0.005 mol·L −1 aqueous solution was mixed with 69 mg of β-cyclodextrin in a 10 mL glass of ofa Naa Na2PdCl2PdCl4 0.0054 0.005 mol mol∙L ∙L aqueous−1 aqueous solution solution was was mixed mixed with with 69 69mg mg of β‐of β‐cyclodextrincyclodextrin in ina 10a 10mL mL flask and the mixture was kept at 70 ◦C for 1 h under magnetic stirring. Then, it was added to the flask glassglass flask flask and and the the mixture mixture was was kept kept at at70 70°C °C for for 1 h 1 underh under magnetic magnetic stirring. stirring. Then, Then, it wasit was added added to to 0.25 mmol of 1-bromo-4-methoxybenzene, 0.25 mmol de bis(pinacolato)diboron, 0.375 mmol of K2CO3, thethe flask flask 0.25 0.25 mmol mmol of of1‐bromo 1‐bromo‐4‐‐methoxybenzene,4‐methoxybenzene, 0.25 0.25 mmol mmol de de bis(pinacolato)diboron, bis(pinacolato)diboron,◦ 0.375 0.375 mmol mmol and 2 mL of solvent (ethanol/H2O 50% or acetonitrile). The system was kept at 70 C for 24 h, and of ofK2 COK2CO3, and3, and 2 mL 2 mL of ofsolvent solvent (ethanol/H (ethanol/H2O2 50%O 50% or oracetonitrile). acetonitrile). The The system system was was kept kept at at70 70°C °C for for 24 24 then the reaction mixture was extracted with dichloromethane and NaCl aqueous saturated solution h, h,and and then then the the reaction reaction mixture mixture was was extracted extracted with with dichloromethane dichloromethane and and NaCl NaCl aqueous aqueous saturated saturated (1:1). After the extraction, the mixture was dried with anhydrous sodium sulfate and evaporated under solutionsolution (1:1). (1:1). After After the the extraction, extraction, the the mixture mixture was was dried dried with with anhydrous anhydrous sodium sodium sulfate sulfate and and reduced pressure. evaporatedevaporated under under reduced reduced pressure. pressure.

SchemeScheme 2. Preliminary 2. Preliminary reaction. reaction.

4.3. Synthesis of Boronic Esters Employing Na PdCl /Cu/Al LDH 4.3.4.3. Synthesis Synthesis of Boronicof Boronic Esters Esters Employing Employing Na Na2PdCl2PdCl4/Cu/Al4/Cu/Al LDH LDH IntoInto a 5 a‐ amL 5 5-mL‐mL screw screw screw cap cap flask cap flask ﬂaskwas was added was added added 0.9 0.9 mmol mmol 0.9 de mmol de bis(pinacolato)diboron, bis(pinacolato)diboron, de bis(pinacolato)diboron, 0.6 0.6 mmol mmol 0.6 de de 1 mmol‐iodo 1‐iodo‐ de‐ 4‐nitrobenzene,1-iodo-4-nitrobenzene,4‐nitrobenzene, 2 mL2 mL of ofsolvent, 2 mLsolvent, of and solvent, and 0.15 0.15 andmmol mmol 0.15 (Cu) mmol (Cu) of ofLDH/Pd (Cu) LDH/Pd of LDH/Pd or or0.15 0.15 mmol or mmol 0.15 (Cu) mmol (Cu) of of (Cu)Cu/Al Cu/Al of LDH Cu/Al LDH −1 LDH and 2 mL of Na PdCl 0.005 mol−1 ·L aqueous solution, Scheme3. In the latter, the percentage of andand 2 mL2 mL of ofNa Na2PdCl2PdCl42 0.0054 0.0054 mol mol∙L ∙L aqueous−1 aqueous solution, solution, scheme scheme 3. 3.In Inthe the latter, latter, the the percentage percentage of of ◦ palladiumpalladium varied variedvaried from from from 2% 2% 2% to to to0.5%. 0.5%. 0.5%. The The The system system system was was was kept kept at 70at70 70°CC °C forfor for 24 24 h 24h under underh under magnetic magnetic magnetic stirring, stirring, stirring, and anditsand its extraction itsextraction extraction was was was done done done as as described asdescribed described in in Supporting inSupporting Supporting Information. Information. Information.

SchemeScheme 3. Model 3. Model reaction. reaction.

5. Conclusions5. Conclusions Cu/AlCu/Al LDH LDH LDH had had had some some some synthesis synthesis synthesis parameters parameters parameters evaluated evaluated evaluated in inorder in order order to toproduce produce the the least least quantity quantity of of byby-products.by‐products.‐products. For For such such material, material, the the list list of ofcontaminants contaminants includes includes the the mineral mineral-likemineral‐like‐like phases phases malachite, malachite, spertiniite,spertiniite, and and nitratine. nitratine. The The catalytic catalytic system system based based on on the the least least-contaminatedleast‐contaminated‐contaminated LDH LDH heterogeneous heterogeneous matrixmatrix and and aqueous aqueous aqueous Na Na Na2PdCl22PdClPdCl4, under4,4 ,under under ligand ligand ligand-free‐free‐free conditions, conditions, conditions, showed showed showed efficient efficient efﬁcient catalytic catalytic catalytic properties properties properties in in theinthe borylation the borylation borylation reactions reactions reactions by by using byusing using bis(pinacolato)diboron bis(pinacolato)diboron bis(pinacolato)diboron as asboron boron as boron precursor. precursor. precursor. This This catalyst This catalyst catalyst system system system can can be canbea promisinga be promising a promising low low‐cost low-cost‐cost alternative alternative alternative for for use for use usein inclassical in classical classical homogeneous homogeneous homogeneous phosphine phosphine phosphine-based‐based‐based systems. systems. systems. AdditionalAdditional experiments experiments to toinvestigate investigate the the possible possible reaction reaction intermediates intermediates and and their their correlation correlation with with thethe LDH LDH structure structure are are under under investigation investigation and and will will be bereported reported in indue due course. course.

SupplementarySupplementary Materials: Materials: The The following following are are available available online online at www.mdpi.com/xxx/s1at www.mdpi.com/xxx/s1: Figure: Figure S1: S1: 1H 1NMRH NMR of of 3, Figure3, Figure S2: S2: 13C 13 NMRC NMR of 3of, Figure3, Figure S3: S3: 1H 1NMRH NMR of 4of, Figure4, Figure S4: S4: 13C 13 NMRC NMR of 4of, Figure4, Figure S5: S5: 1H 1NMRH NMR of 6of, Figure6, Figure S6: S6: 13C13 NMRC NMR of 6of, Figure6, Figure S7: S7: 1H 1NMRH NMR of 7,of Figure7, Figure S8: S8: 13C 13 NMRC NMR of 7of, Figure7, Figure S9: S9: 1H 1NMRH NMR of 8of, Figure8, Figure S10: S10: 13C 13 NMRC NMR of 8of, 8, FigureFigure S11: S11: 1H 1NMRH NMR of 9,of Figure9, Figure S12: S12: 13C 13 NMRC NMR of 9of). 9).

AuthorAuthor Contributions: Contributions: L.C.L.L.F.S. L.C.L.L.F.S. conducted conducted all allthe the borylation borylation reactions. reactions. V.A.N. V.A.N. prepared prepared the the catalysts. catalysts. V.S.R. V.S.R. andand J.B.d.C. J.B.d.C. conducted conducted the the XRD XRD analysis analysis and and the the Rietveld Rietveld refinements. refinements. R.S.F.S. R.S.F.S. and and A.A.d.S. A.A.d.S. conducted conducted the the productproduct characterization. characterization. L.F.B.M. L.F.B.M. and and J.D.S. J.D.S. supervised supervised the the work work and and wrote wrote the the paper. paper.

Catalysts 2019, 9, 302 11 of 12

Additional experiments to investigate the possible reaction intermediates and their correlation with the LDH structure are under investigation and will be reported in due course.

Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4344/9/4/302/s1: Figure S1: 1H NMR of 3, Figure S2: 13C NMR of 3, Figure S3: 1H NMR of 4, Figure S4: 13C NMR of 4, Figure S5: 1H NMR of 6, Figure S6: 13C NMR of 6, Figure S7: 1H NMR of 7, Figure S8: 13C NMR of 7, Figure S9: 1H NMR of 8, Figure S10: 13C NMR of 8, Figure S11: 1H NMR of 9, Figure S12: 13C NMR of 9). Author Contributions: L.C.L.L.F.S. conducted all the borylation reactions. V.A.N. prepared the catalysts. V.S.R. and J.B.d.C. conducted the XRD analysis and the Rietveld refinements. R.S.F.S. and A.A.d.S. conducted the product characterization. L.F.B.M. and J.D.S. supervised the work and wrote the paper. Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES), Finance Code 001. All authors acknowledge the financial support by CNPq and FAPERJ. Specifically, L.F.B.M. would like to thank the funding from CNPq, Universal project code 425613/2016-0, and from FAPERJ, Jovem Cientista do Nosso Estado project code E-26/203.212/2017. Acknowledgments: The authors thank CBPF (Centro Brasileiro de Pesquisas Físicas), UFRJ and UERJ for the analytical support. Conflicts of Interest: The authors declare no conflicts of interest.

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