Mechanistic Insights into Pincer-Ligated Palladium-Catalyzed

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Mechanistic Insights into Pincer-Ligated Palladium-Catalyzed Arylation of Azoles with Aryl Iodides: Evidence of a PdII−PdIV−PdII Pathway Shrikant M. Khake,† Rahul A. Jagtap,† Yuvraj B. Dangat,‡ Rajesh G. Gonnade,§ Kumar Vanka,‡ and Benudhar Punji*,† †

Organometallic Synthesis and Catalysis Group, Chemical Engineering Division, ‡Physical and Materials Chemistry Division, and Centre for Material Characterization, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune 411 008, Maharashtra India §

S Supporting Information *

ABSTRACT: Pincer-based (R2POCNR′2)PdCl complexes along with CuI cocatalyst catalyze the arylation of azoles with aryl iodides to give the 2-arylated azole products. Herein, we report an extensive mechanistic investigation for the direct arylation of azoles involving a well-defined and highly efficient (iPr2POCNEt2)PdCl (2a) catalyst, which emphasizes a rare PdII−PdIV−PdII redox catalytic pathway. Kinetic studies and deuterium labeling experiments indicate that the C−H bond cleavage on azoles occurs via two distinct routes in a reversible manner. Controlled reactivity of the catalyst 2a underlines the iodo derivative (iPr2POCNEt2)PdI (3a) to be the resting state of the catalyst. The intermediate species (iPr2POCNEt2)Pd-benzothiazolyl (4a) has been isolated and structurally characterized. A determination of reaction rates of compound 4a with electronically different aryl iodides has revealed the kinetic significance of the oxidative addition of the C(sp2)−X electrophile, aryl iodide, to complex 4a. Furthermore, the reactivity behavior of 4a suggests that the arylation of benzothiazole proceeds via an oxidative addition/ reductive elimination pathway involving a (iPr2POCNEt2)PdIV(benzothiazolyl)(Ar)I species, which is strongly supported by DFT calculations.

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INTRODUCTION A plethora of transition-metal catalysts (nickel,1 copper,2 rhodium,3 palladium4) are known to catalyze the direct arylation of azoles with aryl halides to give the 2-arylated azoles.5 Among them, the palladium complexes as catalysts have been predominantly utilized, because of the user-friendly nature of palladium precursors and the mild reaction conditions.4 Despite the significant progress in palladium-catalyzed methods, in-depth mechanistic studies for the palladiumcatalyzed arylation of azoles are unfortunately not available.6 An insightful mechanistic understanding of the direct arylation of azoles is essential to the development of novel palladium catalyst systems, which would show increased reactivity at lower temperature and with low catalyst loadings. The absence of a comprehensive mechanistic study for this reaction has led to the consideration of diverse reaction pathways. For instance, an initial oxidative addition of aryl halides to palladium(0), followed by electrophilic aromatic substitution of electron© XXXX American Chemical Society

rich azoles and subsequent reductive elimination, has been proposed (Figure 1A).4a,7 Similarly, Huang and co-workers, as well as others, have described a crucial copper−benzothiazolyl transmetalation to the oxidatively added product LnPdII(Ar)I, before the occurrence of reductive elimination.4j In contrast to other azoles, a ring-opening pathway in the Pd-catalyzed arylation of benzoxazole has been proposed, which is limited only to the benzoxazole system.8 In all of these proposed mechanisms for the arylation of azoles, special attention has been devoted to the C−H bond cleavage step, as the oxidative addition of Ar−X was proposed to occur at the Pd(0) center and the reaction was proposed to proceed via the classical Pd(0)−Pd(II)−Pd(0) catalytic cycle. In contrast to this, a Pd(II)−Pd(IV)−Pd(II) catalytic cycle for the arylation of azoles can be envisioned if a suitable Received: January 4, 2016

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DOI: 10.1021/acs.organomet.6b00003 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

Figure 1. Palladium-catalyzed mechanisms for direct arylation of azoles: (A) previous reports by a classical Pd(0)−Pd(II)−Pd(0) pathway; (B) description in this paper via a Pd(II)−Pd(IV)−Pd(II) pathway.

Scheme 1. Synthesis of POCN-H Ligand Precursors and (R2POCNEt2)PdCl Complexes

(Figure 1B). In addition to the detailed kinetic and controlled reactivity studies and isolation and reactivity of the intermediate species, DFT calculations were performed for the key elementary steps to obtain information about the energetically feasible intermediates during the azole arylation. These investigations have led us to introduce an advanced mechanistic pathway for the direct arylation of azoles with aryl iodides catalyzed by the (iPr2POCNEt2)Pd catalyst.

palladium catalyst system for the arylation reaction is applied. The arylations through the Pd(II)/Pd(IV) process will have many advantages over that with Pd(0)/Pd(II), as in the former, the active catalyst is expected to be highly air and moisture stable and the reaction would exhibit complementary functional group tolerance.9 Similar mechanistic observations have been made for the arylation of other (hetero)arenes, wherein the strongly electrophilic reagents [Ar2I]X10 or aryl halides with stoichiometric amounts of external oxidants were employed.11 Vicente et al. have shown intramolecular C(sp2)−I oxidative addition to a Pd(II) species during a Heck-type reaction,12 and the intermediacy of similar Pd(IV) species is assumed in various other arylation reactions.13 However, the arylation of azoles involving the oxidative addition of C(sp2)−X electrophiles, such as aryl halides, to a Pd(II) derivative has not been documented, though the theoretical work on the Pd(II)/ Pd(IV) process indicates that the oxidative addition of Ph−I to Pd(II) would be feasible if a suitable ligand system were present.14 Recently, we have developed POCN-pincer-ligated palladium catalyst systems for the arylation of azoles with aryl iodides and we made a speculative assertion about the reaction path. 15 Herein, we describe an active, well-defined (iPr2POCNEt2)-pincer palladium derivative and have unraveled the detailed mechanism of the (iPr2POCNEt2)Pd-catalyzed arylation of azoles with aryl iodides, wherein a rare Pd(II)/ Pd(IV)/Pd(II) redox catalytic process has been revealed

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RESULTS AND DISCUSSION

Recently, we have synthesized two arene-based hybrid pincer palladium complexes (iPr2POCNiPr2)PdCl and (tBu2POCNiPr2)PdCl and employed them for the arylation of azoles with aryl iodides.15 These hybrid palladium systems were designed and developed with the assumption that the hemilabile character of the POCN backbone could provide suitable sterics, electronics, and coordination demands that are needed along the different steps of the arylation reaction. At the outset of our studies, we found that the sterically less demanding catalyst (iPr2POCNiPr2)PdCl performed much better than the bulky analogue (tBu2POCNiPr2)PdCl for the direct arylation of azoles. We considered that the sterically even less bulky and electronically distinct complexes, such as ( iPr2 POCN Et2 )PdCl and (Ph2POCNEt2)PdCl, might be superior to the previously employed pincer complexes for the arylation of azoles. B


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Organometallics Synthesis and Characterization of POCN-Palladium Complexes. The iPr2 POCN Et2 -H (3-( i Pr 2 PO)-C 6 H 4 -1(CH2NEt2); 1a) ligand precursor was prepared by a slight modification of the procedure described for the same species by Zargarian and van der Est (Scheme 1).16 Initially, the 3hydroxybenzyl bromide was treated with 2 equiv of diethylamine in acetone to obtain the colorless product of 3((diethylamino)methyl)phenol in excellent yield. 3((Diethylamino)methyl)phenol was well characterized by 1H and 13 C NMR spectroscopy. The treatment of 3((diethylamino)methyl)phenol with NaH at 70 °C, followed by a reaction with diisopropylchlorophosphine (iPr2PCl), produced the ligand iPr2POCNEt2-H as a viscous liquid in 86% yield. The 31P{1H} NMR spectrum of 1a showed a single resonance at 146.6 ppm (for the O−PiPr2 moiety). Other NMR data of compound 1a are in good agreement with those reported for the same species by Zargarian and van der Est.16 Metalation of the crude ligand 1a with Pd(COD)Cl2 in the presence of K3PO4 in 1,4-dioxane at 70 °C afforded the complex ( i P r 2 POCN E t 2 )PdCl ([2-( i Pr 2 PO)-C 6 H 3 -6(CH2NEt2)]PdCl; 2a) as a light yellow solid after purification by column chromatography on neutral alumina (Scheme 1). The 31P{1H} NMR spectrum of 2a displayed a singlet at δ 199.3 ppm, which is comparable with the 31P NMR data reported for the similar compound (iPr2POCNiPr2)PdCl (δP 198.9 ppm). In the 1H NMR spectrum of 2a, the splitting pattern in the aromatic region clearly suggested the formation of a pincer-palladium complex, which is again evident from the disappearance of the peak corresponding to the apical proton. It is worth noting that, in the 1H NMR spectrum of 2a, four protons on two −CH2 groups of −NEt2 appeared as a distinct sextet and a septet, against a single quartet for the same protons in the spectrum of the free ligand. This noticeable change in the splitting pattern of the −CH2 peak in the 1H NMR spectrum could be treated as evidence of the N-arm coordination of the ligand to the palladium center. The 13C NMR, HRMS, and elemental analysis data of 2a are in good agreement with the assigned molecular structure. Compound 2a was further characterized by X-ray crystallography (Figure 2). The coordination geometry around the palladium is approximately square planar. Selected bond lengths and bond angles are given in the figure caption. The Pd−P bond length in 2a is 2.1895(12) Å, almost the same as that observed in (iPr2POCNiPr2)PdCl (Pd−P = 2.1890(6) Å). The Pd−N bond length is 2.192(4) Å, slightly shorter than that reported for (iPr2POCNiPr2)PdCl (Pd−N = 2.2204(17) Å). This value suggests that a stronger coordination of the amino group toward the Pd center in 2a in comparison to that of the same group in the complex (iPr2POCNiPr2)PdCl. The Pd−C and Pd− Cl bond lengths are 1.955(4) and 2.3889(12) Å, respectively, which are comparable with the corresponding bond lengths in (iPr2POCNiPr2)PdCl (Pd−C = 1.956(2), Pd−Cl = 2.3922(6) Å). The P(1)−Pd(1)−N(1) bond angle (162.53(11)°) of 2a is comparable with that reported for ( iPr2POCNiPr2)PdCl (162.10(5)°). The C(1)−Pd−N(1) bond angle is 82.4(2)°, slightly greater than that of (iPr2POCNiPr2)PdCl (81.84(8)°). The N(1)−Pd−Cl(1) bond angle of 2a (97.14(11)°) is significantly smaller than that reported for (iPr2POCNiPr2)PdCl (100.79(5)°), which indicates that the Pd−Cl bond is aligned more toward the amino group in 2a than is the Pd−Cl bond in (iPr2POCNiPr2)PdCl. All of these bond angles seem consistent with the steric impact exerted by the −NEt2 group in 2a being less than that of the −NiPr2 group in (iPr2POCNiPr2)PdCl.

Figure 2. Thermal ellipsoid plot of (iPr2POCNEt2)PdCl (2a). All hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)−C(1), 1.955(4); Pd(1)−P(1), 2.1895(12); Pd(1)−N(1), 2.192(4); Pd(1)−Cl(1), 2.3889(12). Selected bond angles (deg): C(1)−Pd(1)−P(1), 80.08(18); C(1)−Pd(1)−N(1), 82.4(2); P(1)− Pd(1)−N(1), 162.53(11); C(1)−Pd(1)−Cl(1), 175.41(13); P(1)− Pd(1)−Cl(1), 100.30(5); N(1)−Pd(1)−Cl(1), 97.14(11).

The complex (Ph2POCNEt2)PdCl (2b) was previously reported via a one-pot phosphorylation/palladation synthetic route, starting from 3-((diethylamino)methyl)phenol, diphenylchlorophosphine, and palladium chloride, by Song and coworkers,17 without the isolation and characterization of the ligand precursor Ph2POCNEt2-H (1b). However, we have synthesized and characterized the ligand Ph2POCNEt2-H (1b), and the complexation was carried out by the modification of the reported procedure (Scheme 1). Similar to the synthesis of 1a, the ligand precursor Ph2POCNEt2-H (1b) was synthesized from the reaction of 3-((diethylamino)methyl)phenol with diphenylchlorophosphine (Ph2PCl). The compound 1b was obtained as a viscous liquid in 77% yield. The 31P{1H} NMR spectrum of 1b displayed a singlet at 110.1 ppm (for the O-PPh2 moiety), which is consistent with the 31P NMR data reported for an analogous compound: i.e., Ph4POCOP-H18 (δ 112.0 ppm). Metalation of compound 1b with Pd(COD)Cl2 in the presence of K3PO4 in 1,4-dioxane at 70 °C produced the complex (Ph2POCNiPr2)PdCl ([2-(Ph2PO)-C6H3-6-(CH2NEt2)]PdCl; 2b). The 31P{1H} NMR spectrum of 2b showed a single peak at δ 151.5 ppm. The 1H and 13C NMR data of 2b are consistent with the data reported in the literature for the same species.17 Catalytic Activity of Pincer-Ligated Palladium Complexes for Arylation of Azoles. The sterically and electronically distinct hybrid complexes (iPr2POCNEt2)PdCl (2a) and (Ph2POCNEt2)PdCl (2b) along with the most common symmetrical complexes ( iPr4 PCP)PdCl and (iPr4POCOP)PdCl were screened and optimized for the direct arylation of azoles with aryl iodides. After investigating various reaction parameters (see Table S1 in the Supporting Information for details), we found that 0.5 mol % of the catalyst 2a along with CuI (1.0 mol %) catalyzed the arylation of benzothiazole with 4-iodotoluene to produce the arylated product 2-(p-tolyl)benzothiazole (7aa) in 98% yield in the presence of K3PO4 in DMF. With the optimized catalytic conditions, the initial rates for the arylation of benzothiazole using different catalysts (iPr2POCNEt2)PdCl, (iPr2POCNiPr2)PdCl, (tBu2POCNiPr2)PdCl, and (Ph2POCNEt2)PdCl were determined to be 16.0 × 10−4, 9.8 × 10−4, 2.2 × 10−4, and C


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Organometallics 6.2 × 10−4 M min−1, respectively (Figure 3), which strongly supports the hypothesis that the activity of a less bulky

Figure 4. Reaction profile for the 2a-catalyzed arylation of benzothiazole with 4-iodotoluene.

8 TONs, respectively, which suggests the absence of an induction period for the arylation reaction. At the end of 90 min, the conversion of benzothiazole was 48% and the product 7aa formation was 44%. The order in each component in the arylation of benzothiazole with 4-iodotoluene was determined individually at 120 °C in DMF using the initial rate approximation. Figure S1 in the Supporting Information shows that the rate of the arylation reaction is almost the same for the various concentrations of the benzothiazole, suggesting that the reaction is zeroth order in the concentration of benzothiazole. Similarly, the rate of the arylation reaction is independent of the concentration of 4-iodotoluene and establishes zeroth-order behavior for this component (see Figure S2 in the Supporting Information for details). Next, the dependence of the reaction rate on the different loadings of the catalyst 2a was determined by comparison of the initial rates of product formation. A slope of 0.067 was obtained from the plot of log(rate) vs log(concn of 2a), suggesting a zeroth-order reaction in the loading of 2a (Figure S3 in the Supporting Information). The rate of the arylation reaction increases upon higher loadings of K3PO4, and a slope of 0.74 was obtained from the plot of log(rate) vs log(equiv K3PO4), indicating a fractional order arylation reaction in K3PO4 (Figure 5). The partial order in base indicates that more than one pathway is operative for the deprotonation of benzothiazole involving K3PO4 (most likely via direct electrophilic C−H deprotonation of benzothiazole, as well as from the CuI-coordinated benzothiazole). Figure S4 in the Supporting Information shows that the rates of arylation reactions slightly decelerate with an increase in the initial concentration of CuI with a negative order of −0.15. The fractional order of −0.15 indicates that the high concentration of CuI actually retards the rate of the arylation reaction, which might be due to the degradation of the active palladium catalyst at higher concentrations of CuI. A plausible decoordination of the N-arm of the pincer palladium and coordination of the same to CuI can be assumed in the presence of excess CuI, which would reduce the activity of the pincer Pd catalyst.19 On the basis of all these results, the simple rate equation can be written as shown in eq 1.

Figure 3. Time-dependent formation of 7aa using different POCN-Pd catalysts.

(POCN)Pd catalyst is higher than that of the sterically bulky analogues. Though the previously reported catalyst (iPr2POCNiPr2)PdCl was very efficient in the arylation of azoles in the presence of the expensive base Cs2CO3,15 it showed slightly less activity under the current catalytic conditions. The most common symmetrical pincer palladium complexes (iPr4PCP)PdCl and (iPr4POCOP)PdCl were shown to have very poor catalytic performance for the arylation of benzothiazole with 4-iodotoluene and produced the coupled product 7aa in 54% and 22% yields, respectively (see Table S1 for details). With the optimized reaction conditions, the catalyst 2a was employed for the arylation of various substituted benzothiazoles and azoles with diverse aryl iodides to obtain the desired products in moderate to good yields (Table S2 in the Supporting Information). This catalyst system is much more efficient than the literature-reported palladium catalysts for the arylation of azoles in terms of higher turnover numbers.4a,b,f,i In addition, the advantage of the current system is the well-defined nature of the catalyst, which makes it appropriate for an indepth mechanistic study. Kinetic Analysis of Direct Arylation of Azoles Catalyzed by 2a. All kinetic experiments were performed in flame-dried screw-capped tubes under an argon atmosphere. In the standard arylation experiment, 1.25 mM of 2a, 2.50 mM of CuI, 0.108 M mesitylene (internal standard), benzothiazole (0.25 M), 4-iodotoluene (0.375 M), and K3PO4 (0.75 mmol) were used, and DMF was added to make the total volume 2.0 mL. All reactions were conducted at 120 °C, and the progress of the reaction was monitored by gas chromatography (GC) at regular intervals. The reported values represent the average of three independent experiments. The reaction profile of the 2acatalyzed arylation of benzothiazole with 4-iodotoluene over a period of 90 min is shown in Figure 4. The formation of coupled product 7aa followed a linear plot, indicating a constant reaction rate. After 5 and 10 min of the reaction, 4.0 and 10 mM of coupled product was formed amounting to 3 and

rate = k[K3PO4 ]0.74 [CuI]−0.15 overall reaction order = 0.6 D

(1) DOI: 10.1021/acs.organomet.6b00003 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

Figure 5. (A) Time-dependent formation of 7aa at different initial concentrations of K3PO4. (B) Plot of log(rate) vs log(equiv of K3PO4). The rates are the average of three independent measurements.

In order to investigate the possible catalyst deactivation, the recycling experiment of the catalytic reaction system was conducted (section 5.1 in the Supporting Information). After the first catalytic run between benzothiazole and 4-iodotoluene, the yield of the coupled product observed was 98% (GC yield). In the same reaction vessel were placed fresh benzothiazole, 4iodotoluene, and K3PO4, and the reaction was continued further without addition of catalyst 2a and CuI. After 16 h, the yield determined for the second cycle was 90%. Furthermore, the possible catalyst deactivation was investigated by carrying out four arylation reactions at the same [“excess”] but different initial concentrations of the benzothiazole and 4-iodotoluene (section 5.2 in the Supporting Information).20 As shown in Table S9 in the Supporting Information, the rates of the reactions are identical with different starting concentrations of the benzothiazole and 4-iodotoluene, with identical values for [“excess”]. All of these results suggest that there was no significant catalyst deactivation during the arylation reaction of benzothiazole. Turnover-Limiting Step. The progress of the reaction studied with the kinetic analyses reveals that the arylation reaction is zeroth order in benzothiazole, 4-iodotoluene, and the catalyst concentration, whereas a fractional order was observed in K3PO4. Since the arylation reaction is of fractional order in K3PO4, one can assume that the C−H bond cleavage is the probable turnover-limiting step. To probe this possibility, a kinetic isotope effect (KIE) study and a deuterium scrambling experiment were carried out. The rates of the arylation reactions employing 2-H-benzothiazole and 2-D-benzothiazole with 4-iodotoluene were found to be almost consistent, and the observed isotope effect (kH/kD) was approximately 1.0 (Figure S7 in the Supporting Information), which indicates that C−H bond cleavage is unlikely to be the turnover-determining step. Furthermore, the treatment of 2-D-benzothiazole and 2-H-6ethoxybenzothiazole with the optimized catalytic system in the absence of aryl iodide showed a significant H/D scrambling, solely occurring at the C-2 position (section 6.2 and Figure S8 in the Supporting Information). This observation highlights the C−H bond deprotonation to be reversible in nature and hence indicates that it may not be involved in the turnover-limiting step.

The role of a similar (POCN)Pd catalyst, as well as that of CuI, in the arylation reaction has recently been established in our group, wherein (POCN)Pd acts as a catalyst and CuI acts as a cocatalyst.15 Further, the kinetic study for the arylation with varying concentrations of CuI, as well as the control experiments,21 suggest that complex 2a is the primary catalyst and CuI behaves as a cocatalyst. Most likely, the CuI facilitates the transmetalation of the benzothiazolyl moiety to the palladium catalyst in the presence of a base. Furthermore, in order to validate our assumption on the role of CuI, benzothiazole was treated with CuI in acetonitrile, which gave a white crystalline compound. The proton NMR spectrum of the resulting compound displayed a peak at 9.59 ppm corresponding to the C(2)−H proton of the N-coordinated (benzothiazole)CuI moiety (0.18 ppm more deshielded than the signal for free benzothiazole). This coordination could enhance the acidity of the C(2)−H proton, which facilitates the deprotonation/carbometalation of the benzothiazole with the Cu metal followed by transmetalation with the palladium catalyst. A similar role of the organo-copper intermediate has been reported for the arylation of azoles as well as for other coupling reactions.4j,22 Since the C−H bond cleavage/deprotonation was found to be reversible in nature, the rates of the coupling of benzothiazole, 6-ethoxybenzothiazole, and 6-fluorobenzothiazole with 4-iodotoluene were determined in order to understand the electronic influence of the substrates on the arylation reaction (Figure 6). These rates of the coupling reaction were similar, though the substrates are electronically different. Furthermore, the intermolecular competition experiments between the differently substituted benzothiazoles with 4-iodotoluene concurrently furnished the arylation products from both the electron-rich and electron-deficient substrates (Figure S10 in the Supporting Information). These findings indicate that the electronic property of the substituted benzothiazole has negligible influence on the arylation reaction and hence, the probability of transmetalation between (benzothiazolyl)-K and CuX or between (benzothiazolyl)CuLn and (iPr2POCNEt2)PdX being a turnover-limiting step is less likely, because the more electron rich substrates with high nucleophilicity would favor a transmetalation process. Further, these experimental findings do not support reductive E


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Organometallics

Further, the rates of the reaction of the presumed intermediate species (iPr2POCNEt2)Pd(benzothiazolyl) (the synthesis and observation of the same are discussed below) with 4methoxyiodobenzene and 4-acetyliodobenzene were determined by calculating the rate of the formation of (iPr2POCNEt2)PdI species at 100 °C. As shown in Figure 8,

Figure 6. Kinetics of the reactions of benzothiazole (5a), 6ethoxybenzothiazole (5b), and 6-fluorobenzothiazole (5c) with 4iodotoluene (6a).

elimination as a turnover-limiting step, as the reductive elimination tends to be more favorable from electron-poor metal centers.23 The interpretation of the reductive elimination being not a turnover-limiting step was further supported by DFT calculations (discussed below), which show a lower energy barrier for this step. Next, the initial rates for the arylation reaction of benzothiazole with electronically different para-substituted aryl iodides were determined (Figure 7). The Hammett plot was drawn from a correlation between the initial rates and the σp values, which resulted in an almost linear fit with a slope of −0.777. The negative ρ value suggests that a positive charge is being produced in the activated complex and that electrondonating substituents on the aryl iodide will enhance the rate of the arylation reaction. This is in support of the oxidative addition of aryl iodides to a Pd(II) species rather than to a Pd(0) species, as in the former an electron-donating substituent would be expected to stabilize the resulting Pd(IV) intermediate and hence lower the energy of the process.

Figure 8. Time-dependent formation of (iPr2POCNEt2)PdI for the reaction of (iPr2POCNEt2)Pd(benzothiazolyl) with 4-methoxyiodobenzene and 4-acetyliodobenzene at 100 °C. The concentration of (iPr2POCNEt2)PdI was determined from the integration percentage of the same with respect to PMe3 capillary.

the rate of the formation of (iPr2POCNEt2)PdI with use of the electron-rich 4-methoxyiodobenzene is almost double that with the electron-deficient electrophile 4-acetyliodobenzene. This experimental finding further supports our notion that the oxidative addition of aryl iodide occurs to a Pd(II) center, as an electron-rich aryl iodide would favor oxidative addition to a Pd(II) species, and this suggests that the oxidative addition step is kinetically more significant. Controlled Reactivity of Complex 2a. The status of the catalyst 2a under the catalytic conditions was monitored by 31P

Figure 7. (A) Time-dependent formation of arylation products for the coupling of benzothiazole with different para-substituted aryl iodides (4-RC6H4-I). (B) Hammett plot correlation using different aryl iodides. F


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Organometallics Scheme 2. Controlled Reactivity and Resting State of Catalyst 2a

significantly. The observed complex 4a could be a crucial intermediate in the arylation of benzothiazole. This observation further indicated that the reaction of 2a with benzothiazole is most likely the first step of the catalytic reaction, rather than the reaction of 2a with 4-iodotoluene. Reactivity of Active Pd Intermediate 4a. In order to understand the progress of the arylation reaction originating from the intermediate species (iPr2POCNEt2)Pd-benzothiazolyl (4a), the reactivity of 4a with various electrophiles was investigated (Scheme 3). The reaction of 4a (0.013 g, 0.025

NMR spectroscopy to determine the resting state of the catalyst as well as to detect probable intermediate species during the reaction. The 31P NMR experiments were carried out in J. Young NMR tubes, and the yields of different (POCN)Pd species were determined with reference to the external standard (PMe3 capillary). Initially, the catalyst 2a (0.025 mmol), CuI (0.0025 mmol), benzothiazole (0.25 mmol), 4-iodotoluene (0.375 mmol), and K3PO4 (0.375 mmol) in DMF (0.5 mL) were heated to 100 °C in an oil bath and the reaction was monitored at regular intervals (Scheme 2a). After 3 h, the reaction mixture showed 5% of 2a and 95% of (iPr2POCNEt2)PdI (3a) as the 31P NMR detectable species. The reaction mixture was heated further for 40 h, wherein the complex 3a persisted as the major species (91%) with the minor existence of 2a (3%). Even from the 31P NMR measurement of the reaction mixture at 100 °C in the NMR instrument, complex 3a was detected as the major observable species. These observations indicate that the catalyst decomposition was not significant, and further, it demonstrates that the iodide species 3a could be the resting state of the catalyst. Further, with the anticipation of encountering any catalytic intermediate species, we performed control experiments of complex 2a. Hence, complex 2a was treated with 4-iodotoluene (15 equiv) in DMF for 12 h (Scheme 2b). The 31P NMR spectrum of the reaction mixture shows solely the starting complex 2a without any decomposition or formation of the iodide derivative 3a, which suggests that the oxidative addition of 4-iodotoluene to the 16e species 2a might not be a feasible process and such a reaction may not be involved in the first step of the catalytic reaction.24 In another experiment, complex 2a was treated with benzothiazole (10 equiv) in the presence of K3PO4 (Scheme 2c). After the reaction mixture was heated to 100 °C for 3 h, the formation of the new complex (iPr2POCNEt2)Pd-benzothiazolyl (4a) was observed in 19% yield. The authenticity of 4a was established by an independent synthesis and characterization of the same (discussed below). Though the species (iPr2POCNEt2)PdX is significantly stable under standard catalytic conditions, under the aforementioned noncatalytic conditions the palladium species decomposed

Scheme 3. Reactivity of (iPr2POCNEt2)Pd-benzothiazolyl (4a) with Electrophilesa

a

Complex yields are measured from the 31P NMR spectrum (PMe3 capillary as external standard) and coupled products yields are from GC or 1H NMR analysis.

mmol) with 1 equiv of 4-iodotoluene in DMF at elevated temperature exclusively produced the complex (iPr2POCNEt2)PdI (3a) and the coupled product 2-(p-tolyl)benzo[d]thiazole (7aa). This observation again confirmed the intermediacy of 4a during the arylation of benzothiazole with 4-iodotoluene. Further, in order to know the possible pathway in which 4a reacts with 4-iodotoluene, the complex 4a was treated with other strong oxidants, such as I2. Hence, the treatment of 4a with molecular I2 solely produced the complex 3a and 2G


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Organometallics iodobenzo[d]thiazole at room temperature. All of these experimental findings highlight the involvement of a transient Pd(IV) intermediate during the reaction of 4a with 4iodotoluene or molecular iodine, before reductive elimination of the coupled products and generation of the active palladium(II) catalyst. This represents unique experimental evidence, where the oxidative addition of C(sp2)−X electrophile to a Pd(II) center is unequivocally shown. Though the formation of such Pd(IV) species involving C(sp3)−X electrophiles are well documented both experimentally and theoretically,9,25 similar oxidative addition of the C(sp2)−X electrophiles to Pd(II) complexes is rare.12,13 We have further carried out DFT calculations to validate our experimental observations on the probable transient species, which is discussed below. ( iPr2 POCN Et2 )PdX Derivatives. The derivatives of iPr2 ( POCNEt2)Pd were synthesized and characterized to authenticate their presence during the mechanistic investigation (Scheme 4). The reaction of (iPr2POCNEt2)PdCl (2a) with KI

Figure 9. Thermal ellipsoid plot of (iPr2POCNEt2)PdI (3a). All hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)−C(1), 1.965(2); Pd(1)−P(1), 2.1959(7); Pd(1)−N(1), 2.185(2); Pd(1)−I(1), 2.6825(2). Selected bond angles (deg): C(1)−Pd(1)−P(1), 80.21(7); C(1)−Pd(1)−N(1), 82.25(9); P(1)− Pd(1)−N(1), 162.45(6); C(1)−Pd(1)−I(1), 172.74(7); P(1)− Pd(1)−I(1), 99.531(18); N(1)−Pd(1)−I(1), 97.92(6).

Scheme 4. Synthesis of (iPr2POCNEt2)Pd Derivatives

in the dichloromethane/methanol solvent mixture at room temperature afforded the complex (iPr2POCNEt2)PdI (3a). The 31 P NMR spectrum of 3a showed a single peak at 205.4 ppm. The complex (iPr2POCNEt2)Pd(benzothiazolyl) (4a) was synthesized by the treatment of 2a with 5 equiv of benzothiazolyllithium at −78 °C. The 31P NMR spectrum of complex 4a showed a singlet at 196.0 ppm. The HRMS-ESI mass spectrum of 4a displayed a peak at m/z 535.1169 corresponding to the [4a + H]+ ion. The 1H and 13C NMR and elemental analysis data of complexes 3a and 4a are in good agreement with the assigned molecular structures. Molecular structures of complexes 3a and 4a were also determined by X-ray single-crystal analysis. The thermal ellipsoid plots of the molecules are shown in Figures 9 and 10. The selected bond lengths and bond angles are given in the respective figure captions. In general, the structural parameters of 3a and 4a are quite similar to those of 2a. The Pd−C(ipso) bond lengths in 3a and 4a are 1.965(2) and 1.985(2) Å, respectively. The differences in Pd−C(ipso) bond lengths are indicative of the different trans influences of X ligands on the complex, and they are in the order benzothiazolyl (4a) > I (3a) > Cl (2a). The C−Pd−P and C−Pd−N bond angles in all the complexes are almost similar, except that a slightly smaller P− Pd−N bond angle (161.6°) was observed in 4a. In complex 4a, the benzothiazolyl moiety is almost perpendicular to the POCN-pincer ring, having both N(1)−Pd(1)−C(18)−N(2) and P(1)−Pd(1)−C(18)−S(1) torsion angles of around 70°.

Figure 10. Thermal ellipsoid plot of (iPr2POCNEt2)Pd(benzothiazolyl) (4a). All hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)−C(1), 1.985(2); Pd(1)−P(1), 2.1953(6); Pd(1)−N(1), 2.181(2); Pd(1)−C(18), 2.072(2). Selected bond angles (deg): C(1)−Pd(1)−P(1), 80.30(7); C(1)−Pd(1)−N(1), 81.31(9); P(1)− Pd(1)−N(1), 161.60(6); C(1)−Pd(1)−C(18), 174.46(10); P(1)− Pd(1)−C(18), 99.70(7); N(1)−Pd(1)−C(18), 98.58(8).

Quantum-Chemical Calculations. In order to get more insight into the reactivity pattern of aryl iodide with the intermediate palladium complex 4a, the reaction of iodobenzene (RC1) with the square planar palladium complex 4a has been investigated through density functional theory (DFT). The two steps (i) oxidative addition and (ii) reductive elimination have been considered. (i). Oxidative Addition. The oxidative addition of aryl iodide (RC1) can occur through four different possibilities. The transition states for these different possibilities have been explored. As shown in Figure 11, out of the four different H


Article

Organometallics

Figure 11. Four different possible transition states for the oxidative addition of RC1 to 4a. All values are in kcal/mol and are with respect to (RC1+4a). Hydrogen atoms are omitted for the purpose of clarity. The color scheme is as follows: palladium, brown; iodide, maroon; sulfur, dark yellow; phosphorus, light yellow; nitrogen, blue; oxygen, red; carbon, black.

Figure 12. Free energy profile for the reaction of phenyl iodide (RC1) with 4a. All values are in kcal/mol. Hydrogen atoms are omitted for the purpose of clarity. The color scheme is as follows: palladium, brown; iodide, maroon; sulfur, dark yellow; phosphorus, light yellow; nitrogen, blue; oxygen, red; carbon, black.

transition states the transition state TS1 is lower in energy than the transition states TS1a, TS1b, and TS1c by 3.1, 10.7, and 15.6 kcal/mol, respectively. Thus, the addition of aryl iodide (RC1) to 4a proceeds via TS1, leading to the octahedral intermediate IM, which is endergonic by 20.0 kcal/mol, as shown in Figure 12. (ii). Reductive Elimination. The octahedral intermediate (IM) is an unstable species (20.0 kcal/mol endergonic). The formation of a C−C bond is feasible through the transition state TS2 via a barrier of 12.9 kcal/mol. This reductive elimination process yields the iodated Pd complex 3a and the C−C coupled product 7as, with the reaction being exergonic by 45.8 kcal/mol with respect to the starting reactant, as shown in Figure 12. It is also clear from the figure that the barrier for the key step of the overall reaction of RC1 with 4a is 32.9 kcal/mol. Therefore, under the given experimental conditions of elevated temperature (120 °C), this process would be expected to be

feasible. The HOMO−LUMO gap and the energy values of the frontier orbitals for all the intermediates and transition states (shown in Figure 12) are presented in Table S11 in the Supporting Information. The possibility of a concerted pathway for the formation of 3a and 7as from the reaction of phenyl iodide (RC1) with 4a has also been investigated. All attempts to find the concerted transition state led either to the formation of IM or back to the reactants. The concerted pathway is likely to be an energetically unfavorable process, due to steric hindrance. Hence, our calculations suggest a stepwise pathway. Therefore, the corroboration with experimental results suggests that the palladium complex is able to go through oxidative addition and reductive elimination reactions, with the formation of a stable octahedral Pd complex (IM), where the palladium exists in the +4 oxidation state. A similar observation of the palladium being in the +4 oxidation state via the C(sp2)− I


Article

Organometallics

Figure 13. Proposed arylation pathway for benzothiazole with aryl iodides catalyzed by (POCN)PdX.

arylation of azoles with aryl iodides involving a well-defined hybrid POCN-pincer palladium catalyst. Kinetic measurements, reactivity studies, and DFT calculations on the arylation reaction strongly support a Pd(II)/Pd(IV)/Pd(II) redox process for the reaction, which occurs via the oxidative addition of the C(sp2)−X electrophile, aryl iodide, to the (POCN)PdII species. Intermolecular competition experiments between the electronically distinct azoles and their comparative kinetic studies for the arylation reaction establish that the electronic properties on azoles are kinetically not relevant. The isolation and characterization of a catalytically pertinent intermediate (iPr2POCNEt2)Pd(benzothiazolyl) complex allowed the explicit demonstration of the mechanistic pathway. Kinetic and reactivity studies of this species are consistent with the oxidative addition of aryl iodide electrophile to the Pd(II) species being a kinetically important step for the arylation reaction. All these studies provided a significant mechanistic insight into the direct arylation of azoles with aryl iodides, which could shed light into the palladium-catalyzed C−H bond arylation of other arenes and heteroarenes.

X electrophilic oxidative addition to a Pd(II) center has rarely been documented.12,13 Probable Catalytic Cycle. On the basis of the experimental results and DFT studies described above, and from the earlier observations of our group15 and others,4a,j a validated catalytic cycle can be drawn for the (iPr2POCNEt2)PdCl (2a) catalyzed arylation of azoles with aryl iodides (Figure 13). First, the benzothiazole coordinates to CuX to form the copper complex A, followed by deprotonation and rearrangement to generate the species B. K 3 PO 4 most likely deprotonates the free benzothiazole, in addition to the benzothiazole coordinated to CuX, because the reaction is of a fractional order with respect to the concentration of K3PO4. This is also evident from the deuterium scrambling between 2D-benzothiazole and 2-H-6-ethoxybenzothiazole, which occurs even in the absence of CuI. The copper−benzothiazolyl species B then undergoes transmetalation with the (iPr2POCNEt2)PdX, leading to complex 4a. The generated palladium−benzothiazolyl complex 4a then oxidatively reacts with the aryl iodide to produce the octahedral species (iPr2POCNEt2)PdIV(benzothiazolyl)(Ar)I (C). The reductive elimination of the coupled product from species C will regenerate the catalyst (iPr2POCNEt2)PdX. DFT calculations, as well as the experimental results, strongly support the involvement of a transient (iPr2POCNEt2)PdIV intermediate via the oxidative addition of aryl iodide to the (iPr2POCNEt2)PdII species. Though there exist a number of reports on the arylation of azoles by palladium catalysts, all of them have shown a conventional Pd(0)/Pd(II) redox process with little experimental input. We have, on the other hand, elaborately demonstrated here a new mechanistic avenue for the arylation of azoles by installing a suitable ligand on the palladium. The reactions occurs via a Pd(II)−Pd(IV)− Pd(II) pathway with C(sp2)−X aryl iodide oxidative addition to the Pd(II) species. Though our experimental findings strongly support the Pd(II)/Pd(IV) redox process for the arylation reaction, a parallel Pd(0)/Pd(II) cycle via the decomposition of a small amount of 2a to Pd(0) cannot be completely ruled out.

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EXPERIMENTAL SECTION

General Experimental Considerations. All manipulations were conducted under an argon atmosphere either in a glovebox or using standard Schlenk techniques in predried glassware. The catalytic reactions were performed in flame-dried reaction vessels with a Teflon screw cap. Solvents were dried over Na/benzophenone or CaH2 and distilled prior to use. DMF was dried over CaH2, distilled under vacuum, and stored over 4 Å molecular sieves. Liquid reagents were flushed with argon prior to use. (iPr2PCPiPr2)PdCl,26 (iPr2POCOPiPr2)PdCl,27 3-hydroxybenzyl bromide,28 5-methylbenzoxazole,29 5-arylazoles,30 and 6-substituted benzothiazole31 were synthesized according to previously described procedures. All other chemicals were obtained from commercial sources and were used without further purification. Yields refer to isolated compounds, estimated to be >95% pure as determined by 1H NMR. TLC: TLC silica gel 60 F254, detection under UV light at 254 nm. Chromatography: separations were carried out on Spectrochem silica gel (0.120−0.250 mm, 60−120 mesh) or neutral alumina (Al2O3). High-resolution mass spectroscopy (HRMS) was carried out on a Thermo Scientific Q-Exactive, Accela 1250 pump. Melting points were determined on a Büchi 540 capillary melting point apparatus; values are uncorrected. NMR (1H and 13C) spectra were recorded at 400 or 500 MHz (1H), 100 or 125 MHz (13C, DEPT (distortionless enhancement by polarization transfer)), 377 MHz

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CONCLUSION In summary, we have performed an in-depth mechanistic study and demonstrated an unusual mechanistic avenue for the direct J


Article

Organometallics (19F), and 162 or 202 MHz (31P{1H}) on Bruker AV 400 and AV 500 spectrometers in CDCl3 solutions, if not otherwise specified; chemical shifts (δ) are given in ppm. The 1H and 13C NMR spectra are referenced to residual solvent signals (CDCl3: δ(H) 7.26 ppm, δ(C) 77.2 ppm), and 31P{1H} NMR chemical shifts are referenced to an external standard, Me3P in p-xylene-d10 solvent (δ −62.4 ppm), in a sealed capillary tube. The synthesis and characterization data of the pincer precursors 3-((diethylamino)methyl)phenol, (iPr2POCNEt2)-H (1a) and ( Ph2 POCN Et2 )-H (1b) and palladium complexes (iPr2POCNEt2)PdCl (2a), (Ph2POCNEt2)PdCl (2b), (iPr2POCNEt2)PdI (3a), and (iPr2POCNEt2)Pd-benzothiazolyl (4a) are given in the Supporting Information. Computational Details. All DFT calculations were carried out using the Turbomole 6.0 suite of programs.32 Geometry optimizations were performed using the dispersion corrected Perdew, Burke, and Erzenhof density functional (PBE).33 The TZVP basis set was employed for the calculations.34 The resolution of identity (ri),35 along with the multipole accelerated resolution of identity (marij)36 approximations were employed for an accurate and efficient treatment of the electronic Coulomb term in the density functional calculations. Solvent effects were incorporated with the COSMO model,37 with ε = 2.25 for 1,4-dioxane. The contributions of internal energy and entropy were obtained from frequency calculations done on the DFT structures at 298.15 K. Therefore, the energies reported in the figures are the ΔG values. It was ensured that the obtained transition state structures possessed only one imaginary frequency corresponding to the correct normal mode. The translational entropy term in the calculated structures was corrected through a free volume correction introduced by Mammen et al.38 This procedure of correcting the translational entropy term has also been followed by other groups.39

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Chem., Int. Ed. 2010, 49, 2202−2205. (d) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. ChemCatChem 2010, 2, 1403−1406. (e) Yamamoto, T.; Muto, K.; Komiyama, M.; Canivet, J.; Yamaguchi, J.; Itami, K. Chem. - Eur. J. 2011, 17, 10113−10122. (f) Yamaguchi, J.; Muto, K.; Itami, K. Eur. J. Org. Chem. 2013, 2013, 19−30. (2) Fox examples of Cu-catalyzed arylation, see: (a) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 12404−12405. (b) Kulkarni, A. A.; Daugulis, O. Synthesis 2009, 4087−4109. (c) Han, Y.; Wang, X.; Wang, X.; Lv, L.; Diao, G.; Yuan, Y. Synthesis 2012, 44, 3027−3032. (3) Fox examples of Rh-catalyzed arylation, see: (a) Lewis, J. C.; Wiedemann, S. H.; Bergman, R. G.; Ellman, J. A. Org. Lett. 2004, 6, 35−38. (b) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2008, 41, 1013−1025. (4) For selected examples of Pd-catalyzed arylation, see: (a) PivsaArt, S.; Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71, 467−473. (b) Bellina, F.; Cauteruccio, S.; Rossi, R. Eur. J. Org. Chem. 2006, 2006, 1379−1382. (c) Bellina, F.; Calandri, C.; Cauteruccio, S.; Rossi, R. Tetrahedron 2007, 63, 1970−1980. (d) Besselièvre, F.; Mahuteau-Betzer, F.; Grierson, D. S.; Piguel, S. J. Org. Chem. 2008, 73, 3278−3280. (e) Campeau, C.; Bertrand-Laperle, M.; Leclerc, J.-P.; Villemure, E.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 3276−3277. (f) Ackermann, L.; Althammer, A.; Fenner, S. Angew. Chem., Int. Ed. 2009, 48, 201−204. (g) Ackermann, L.; Barfüsser, S.; Pospech, J. Org. Lett. 2010, 12, 724−726. (h) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269−10310. (i) Shibahara, F.; Yamaguchi, E.; Murai, T. Chem. Commun. 2010, 46, 2471−2473. (j) Huang, J.; Chan, J.; Chen, Y.; Borths, C. J.; Baucom, K. D.; Larsen, R. D.; Faul, M. M. J. Am. Chem. Soc. 2010, 132, 3674−3675. (k) Zhang, G.; Zhao, X.; Yan, Y.; Ding, C. Eur. J. Org. Chem. 2012, 2012, 669−672. (l) Yu, D.; Lu, L.; Shen, Q. Org. Lett. 2013, 15, 940− 943. (m) Kozhushkov, S. I.; Potukuchi, H. K.; Ackermann, L. Catal. Sci. Technol. 2013, 3, 562−571. (n) Shen, X.-B.; Zhang, Y.; Chen, W.X.; Xiao, Z.-K.; Hu, T.-T.; Shao, L.-X. Org. Lett. 2014, 16, 1984−1987. (o) Gao, F.; Kim, B.-S.; Walsh, P. J. Chem. Commun. 2014, 50, 10661− 10664. (p) Ferguson, D. M.; Rudolph, S. R.; Kalyani, D. ACS Catal. 2014, 4, 2395−2401. (q) Tani, S.; Uehara, T. N.; Yamaguchi, J.; Itami, K. Chem. Sci. 2014, 5, 123−135. (r) Pandey, D. K.; Khake, S. M.; Gonnade, R. G.; Punji, B. RSC Adv. 2015, 5, 81502−81514. (s) Zhu, F.; Wang, Z.-X. Org. Lett. 2015, 17, 1601−1604. (5) For selected reviews of the direct arylation, see: (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174−238. (b) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792−9826. (c) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009, 38, 2447−2464. (d) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147−1169. (e) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624−655. (f) Ackermann, L. Chem. Rev. 2011, 111, 1315−1345. (g) Kuhl, N.; Hopkinson, M. N.; WencelDelord, J.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 10236−10254. (h) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879−5918. (i) Wu, Y.; Wang, J.; Mao, F.; Kwong, F. Y. Chem. - Asian J. 2014, 9, 26−47. (j) Zhang, F.; Spring, D. R. Chem. Soc. Rev. 2014, 43, 6906−6919. (6) (a) Bellina, F.; Cauteruccio, S.; Rossi, R. Curr. Org. Chem. 2008, 12, 774−790. (b) Verrier, C.; Lassalas, P.; Théveau, L.; Quéguiner, G.; Trécourt, F.; Marsais, F.; Hoarau, C. Beilstein J. Org. Chem. 2011, 7, 1584−1601. (c) Wakioka, M.; Nakamura, Y.; Hihara, Y.; Ozawa, F.; Sakaki, S. Organometallics 2013, 32, 4423−4430. (d) Wakioka, M.; Nakamura, Y.; Hihara, Y.; Ozawa, F.; Sakaki, S. Organometallics 2014, 33, 6247−6252. (7) Chiong, H. A.; Daugulis, O. Org. Lett. 2007, 9, 1449−1451. (8) Sánchez, R. S.; Zhuravlev, F. A. J. Am. Chem. Soc. 2007, 129, 5824−5825. (9) For a recent review of organopalladium(IV) chemistry, see: Xu, L.-M.; Li, B.-J.; Yang, Z.; Shi, Z.-J. Chem. Soc. Rev. 2010, 39, 712−733. (10) For selected examples, see: (a) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330−7331. (b) Deprez, N. R.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 4972−4973. (c) Deprez, N. R.; Sanford, M. S. Inorg.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.6b00003. Detailed experimental procedures, analytical data for compounds, and 1H and 13C NMR spectra of new compounds (PDF) Crystallographic data for 2a (CCDC-1423294) (CIF) Crystallographic data for 3a (CCDC-1423296) (CIF) Crystallographic data for 4a (CCDC-1423295) (CIF)

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AUTHOR INFORMATION

Corresponding Author

*B.P.: tel, +91-20-2590 2733; fax, +91-20-2590 2621; e-mail, b. [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was financially supported by the SERB, New Delhi, India (SR/S1/IC-42/2012). We are grateful to the Alexander von Humboldt Foundation of Germany for an equipment grant. S.M.K. and R.A.J. thank the CSIR -New Delhi and UGCNew Delhi, respectively, for research fellowships. We are grateful to Dr. P. R. Rajmohanan for NMR facilities, Dr. (Mrs.) Shanthakumari for HRMS analyses, and Dr. S. P. Borikar for GC-MS analyses.

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REFERENCES

(1) Fox examples of Ni-catalyzed arylation, see: (a) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009, 11, 1737−1740. (b) Canivet, J.; Yamaguchi, J.; Ban, I.; Itami, K. Org. Lett. 2009, 11, 1733−1736. (c) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Angew. K


Article

Organometallics

(32) Ahlrichs, R.; Bär, M.; Häser, M.; Horn, H.; Kölmel, C. Chem. Phys. Lett. 1989, 162, 165−169. (33) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77, 3865−3868. (34) Weigend, F. Phys. Chem. Chem. Phys. 2002, 4, 4285−4291. (35) Eichkorn, K.; Treutler, O.; Ö hm, H.; Häser, M.; Ahlrichs, R. Chem. Phys. Lett. 1995, 240, 283−290. (36) Sierka, M.; Hogekamp, A.; Ahlrichs, R. J. Chem. Phys. 2003, 118, 9136−9148. (37) Klamt, A. J. Phys. Chem. 1995, 99, 2224−2235. (38) Mammen, M.; Shakhnovich, E. I.; Deutch, J. M.; Whitesides, G. M. J. Org. Chem. 1998, 63, 3821−3830. (39) (a) Kelly, E.; Seth, M.; Ziegler, T. J. Phys. Chem. A 2004, 108, 2167−2180. (b) Janse van Rensburg, W.; Grové, C.; Steynberg, J. P.; Stark, K. B.; Huyser, J. J.; Steynberg, P. J. Organometallics 2004, 23, 1207−1222. (c) Bagno, A.; Kantlehner, W.; Kress, R.; Saielli, G.; Stoyanov, E. J. Org. Chem. 2006, 71, 9331−9340. (d) Williams, V. M.; Kong, J. R.; Ko, B. J.; Mantri, Y.; Brodbelt, J. S.; Baik, M.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 16054−16062. (e) Qi, Y.; Dong, Q.; Zhong, L.; Liu, Z.; Qiu, P.; Cheng, R.; He, X.; Vanderbilt, J.; Liu, B. Organometallics 2010, 29, 1588−1602. (f) Yin, H.; Wang, D.; Valiev, M. J. Phys. Chem. A 2011, 115, 12047−12052. (g) Li, J.-N.; Pu, M.; Ma, C.-C.; Tian, Y.; He, J.; Evans, D. G. J. Mol. Catal. A: Chem. 2012, 359, 14−20. (h) Dangat, Y.; Rizvi, M. A.; Pandey, P.; Vanka, K. J. Organomet. Chem. 2016, 801, 30−41.

Chem. 2007, 46, 1924−1935. (d) Deprez, N. R.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 11234−11241. (e) Szabó, K. J. J. Mol. Catal. A: Chem. 2010, 324, 56−63. (f) Hickman, A. J.; Sanford, M. S. ACS Catal. 2011, 1, 170−174. (11) (a) Daugulis, O.; Zaitsev, V. G. Angew. Chem., Int. Ed. 2005, 44, 4046−4048. (b) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154−13155. (c) Zhang, Q.; Chen, K.; Rao, W.; Zhang, Y.; Chen, F.-J.; Shi, B.-F. Angew. Chem., Int. Ed. 2013, 52, 13588−13592. (d) Gong, W.; Zhang, G.; Liu, T.; Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 16940−16946. (e) Arroniz, C.; Denis, J. G.; Ironmonger, A.; Rassias, G.; Larrosa, I. Chem. Sci. 2014, 5, 3509−3514. (f) Dastbaravardeh, N.; Toba, T.; Farmer, M. E.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, 9877−9884. (12) (a) Vicente, J.; Arcas, A.; Juliá-Hernández, F.; Bautista, D. Angew. Chem., Int. Ed. 2011, 50, 6896−6899. A similar example: (b) Vicente-Hernandez, I.; Chicote, M.-T.; Vicente, J.; Bautista, D. Chem. Commun. 2016, 52, 594−596. (13) (a) Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2010, 132, 3965−3972. (b) Maestri, G.; Motti, E.; Della Ca’, N.; Malacria, M.; Derat, E.; Catellani, M. J. Am. Chem. Soc. 2011, 133, 8574−8585. (14) Sundermann, A.; Uzan, O.; Martin, J. M. L. Chem. - Eur. J. 2001, 7, 1703−1711. (15) Khake, S. M.; Soni, V.; Gonnade, R. G.; Punji, B. Dalton Trans. 2014, 43, 16084−16096. (16) Spasyuk, D. M.; Zargarian, D.; van der Est, A. Organometallics 2009, 28, 6531−6540. (17) Gong, J.-F.; Zhang, Y.-H.; Song, M.-P.; Xu, C. Organometallics 2007, 26, 6487−6492. (18) Salah, A. B.; Zargarian, D. Dalton Trans. 2011, 40, 8977−8985. (19) An attempt to isolate the presumed Pd−Cu bimetallic species was unfortunately not successful. The reaction of compound 2a with an excess of CuI produced 21% of (POCN)PdI as the exclusive new species. (20) Blackmond, D. G. Angew. Chem., Int. Ed. 2005, 44, 4302−4320. (21) The arylation reaction under the standard reaction conditions in the absence of CuI gave

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