Dalton Transactions View Article Online
Published on 20 August 2014. Downloaded by Michigan Technological University on 22/10/2014 05:08:52.
PAPER
Cite this: Dalton Trans., 2014, 43, 16084
View Journal | View Issue
Design and development of POCN-pincer palladium catalysts for C–H bond arylation of azoles with aryl iodides† Shrikant M. Khake,a Vineeta Soni,a Rajesh G. Gonnadeb and Benudhar Punji*a Well-defined and efficient POCN-ligated palladium complexes have been developed for the direct C–H bond arylation of azoles with aryl iodides. The phosphinite-amine pincer ligands 1-(R2PO)-C6H4-3(CH2NiPr2) [R2POCNiPr2-H; R = iPr (1a), R = tBu (1b)] and corresponding palladium complexes {2-(R2PO)C6H3-6-(CH2NiPr2)}PdCl [(R2POCNiPr2)PdCl; R = iPr (2a), R = tBu (2b)] were synthesized in good yields. Treatment of palladium complex 2a with KI and AgOAc afforded the complexes (iPr2POCNiPr2)PdI (3a) and (iPr2POCNiPr2)Pd(OAc) (4a), respectively. Similarly, the reaction of 2a with benzothiazolyl-lithium produces the (iPr2POCNiPr2)Pd(benzothiazolyl) (5a) complex in a quantitative yield. The pincer palladium complex 2a efficiently catalyzes the C–H bond arylation of benzothiazole, substituted-benzoxazoles and 5-aryl oxazoles with diverse aryl iodides in the presence of CuI as a co-catalyst under mild reaction conditions. This represents the first example of a pincer palladium complex being applied for the direct
Received 26th May 2014, Accepted 19th August 2014
C–H bond arylation of any heterocycle with low catalyst loading. A preliminary mechanistic investigation
DOI: 10.1039/c4dt01547a
reveals that palladium nanoparticles are presumably not the catalytically active form of 2a and supports the direct involvement of the catalyst 2a, with complex 5a being a probable key intermediate in the cata-
www.rsc.org/dalton
lytic reaction.
Introduction Direct C–H bond functionalization of heteroarenes has raised much interest as an alternative to traditional cross-coupling reactions, because such a process bypasses pre-activation steps such as the halogenation or metallation of heteroarenes.1 The transition metal-catalyzed C–H bond functionalizations, like arylation, alkenylation, alkynylation and alkylation, of various heteroarenes have been widely explored over the last few years.2 Most importantly, the arylation of azoles has received particular attention, as arylated azoles are essential building blocks of diverse biological and pharmaceutical compounds.3 The C-2 arylations of azoles to synthesize 2-arylated azoles have been
a Organometallic Synthesis and Catalysis Group, Chemical Engineering Division, CSIR–National Chemical Laboratory (CSIR–NCL), Dr. Homi Bhabha Road, Pune – 411 008, Maharashtra, India. E-mail: [email protected]; Fax: +91-20-25902621; Tel: +91-20-2590 2733 b Centre for Material Characterization, CSIR–National Chemical Laboratory (CSIR–NCL), Dr. Homi Bhabha Road, Pune – 411 008, Maharashtra, India † Electronic supplementary information (ESI) available: Details of the experimental data and NMR spectra of all compounds, crystal structure data of complexes 2a and 2b, and the 31P{1H} NMR spectrum of the (iPr2POCNiPr2)Pd species during the arylation of azole, demonstrating the catalyst resting state. CCDC 973533 and 973534. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4dt01547a
16084 | Dalton Trans., 2014, 43, 16084–16096
realized by the employment of various transition metal salts with suitable ligand sets.4 Among them, the most convenient and inexpensive transition metal catalysts, such as complexes of nickel5 and copper,6 represent a very important development for the arylation of azoles in terms of the catalyst cost for large scale synthesis. However, in most cases the utilization of strong bases and harsh reaction conditions limits the further advancement of those methodologies. The arylation of azoles has also been reported under mild conditions employing precious metal catalysts, like Ru,2j Rh,7 or Pd,8 where high loading of the catalyst (>5 mol%) is essential for the completion of reactions. Moreover, many of these catalysts were generated in situ (not “welldefined”) with few exceptions;8l hence limiting the proper understanding of the catalyst’s reactivity and reaction system. Although many of these in situ generated catalysts are convenient for the arylation of various azoles, there is still a demand to develop well-defined catalyst which can execute the same tasks with minimal catalyst loading. Herein, our objective is to develop well-designed, well-characterized and competent palladium catalysts for the direct C–H bond arylation of azoles, as in many cases such catalysts are more efficient than the transformations carried out by metal salts and added ligands. Pincer-ligated transition metal catalysts have shown exceptionally high thermal stability and catalytic activity for various important organic transformations in comparison with the tra-
This journal is © The Royal Society of Chemistry 2014
View Article Online
Published on 20 August 2014. Downloaded by Michigan Technological University on 22/10/2014 05:08:52.
Dalton Transactions
Chart 1
Paper
General representation of pincer palladium complexes.
ditional mono- or bi-dentate ligated transition metal catalysts; as the tight tridentate coordination in the pincer system keeps the metal and ligand together in each catalytic step, where the ligand effects are conveniently transferred to the metal center (Chart 1).9 For example, the PCP pincer palladium complexes, [{2,6-(iPr2PCH2)2-C6H3}Pd(OCOCF3)] and [{2,6-(iPr2PCH2)2-3,5(CH3)2-1-CH2-C6H}Pd(OCOCF3)], are highly active catalysts for the Heck coupling reaction with bromo- and iodo-arene electrophiles;10 whereas a phosphinite-based POCOP pincer palladium catalyst, [{2,6-(iPr2PO)2-C6H3}PdCl], shows efficient activity for the coupling of styrene with relatively difficult aryl chloride electrophiles.11 Similarly, aminophosphine-based pincer palladium complexes, [{2,6-(EP(piperidinyl)2)2-C6H3}PdCl] (E = NH, O), and an adamantyl core palladium complex, [{2,6(Cy2PCH2)2-C10H13}PdCl], are extremely efficient catalysts for Suzuki cross-coupling reactions.12 Driven by the high thermal stability and extraordinary catalytic efficiency of pincer palladium complexes for the Suzuki and Heck coupling reactions, we became fascinated in developing a novel pincer palladium catalyst for C–C bond forming reactions via direct C–H bond functionalization. As many of these pincer palladium catalysts are assumed to follow a Pd(II)–Pd(IV)–Pd(II) catalytic pathway during cross-coupling reactions,12b a pincer-ligated palladium complex with a strong σ-donor atom on the ligand would enhance the electrophilic oxidative addition at the Pd(II) center and stabilize the Pd(IV) species.13 Furthermore, transmetallation and electrophilic attack have opposing electron demands during such catalysis. Hence, we envisioned that an amino-phosphinite ligand,14 where the electron-rich hard donor amino side and phosphinite segment would assist in electrophilic addition and transmetallation, respectively, could be an ideal system to stabilize the catalytically active palladium species in the higher oxidation state,15 which can lead to a high conversion rate with low catalyst loading. With these hypotheses, herein, we have synthesized a “hybrid” pincer palladium catalyst system which efficiently catalyzes the arylation of various azoles with aryl iodides with low catalyst loading in the presence of CuI as a cocatalyst. The preliminary mechanistic investigation has been carried out to gain an insight into the catalyst’s behaviour and reaction pathway.
bromide (Scheme 1). First, 3-hydroxy benzyl bromide was treated with two equivalents of diisopropyl amine in acetone to obtain the colorless product of 3-((diisopropylamino)methyl)phenol in 82% isolated yield. This compound was characterized by 1H and 13C NMR spectroscopy as well as HRMS. The treatment of 3-((diisopropylamino)methyl)phenol with NaH, followed by reaction with dialkylchlorophosphine, R2PCl (R = iPr, tBu) produced the ligands {1-(R2PO)-C6H4-3(CH2NiPr2)}, R2POCNiPr2-H (R = iPr, 1a; R = tBu, 1b), as colorless viscous liquids in excellent yields. The 31P{1H} NMR spectrum of 1a displayed a peak at 148.8 ppm (for the O-PiPr2 moiety), whereas that of 1b displayed a peak at 154.3 ppm (for the O-PtBu2 moiety). These NMR values of 1a and 1b are consistent with the 31P NMR data reported for similar compounds i.e. iPr4POCOP-H16 (δ 149.0 ppm) and tBu4POCOP-H17 (δ 153.1 ppm), respectively. These crude viscous liquids were used for the metallation reactions without further purification. The metallation of the ligand iPr2POCNiPr2-H with Pd(COD)Cl2 in the presence of K3PO4 in 1,4-dioxane under refluxing conditions gave {2-(iPr2PO)-C6H3-6-(CH2NiPr2)}PdCl, (iPr2POCNiPr2)PdCl (2a), as an air-stable light yellow solid. The 31P{1H} NMR spectrum of 2a shows a singlet at δ 198.9 ppm (cf. (iPr4POCOP)PdCl,16 δ 187.7 ppm). The 1H NMR spectrum of compound 2a shows signals for only three protons in the aromatic region, with the disappearance of the signal corresponding to the apical proton, which clearly indicates the formation of the pincer palladium complex. Similarly, the complexation of tBu2 POCNiPr2-H with Pd(COD)Cl2 in the presence of K3PO4 in toluene under refluxing conditions produced {2-(tBu2PO)-C6H36-(CH2NiPr2)}PdCl, (tBu2POCNiPr2)PdCl (2b), as a yellow solid in
Results and discussion Synthesis of the POCN-H ligands and palladium complexes The R2POCNiPr2-H {1-(R2PO)-C6H4-3-(CH2NiPr2)} ligands were synthesized in two steps starting from 3-hydroxy benzyl
This journal is © The Royal Society of Chemistry 2014
Scheme 1 Synthesis of the (R2POCNiPr2)-H ligands and (R2POCNiPr2) PdCl complexes.
Dalton Trans., 2014, 43, 16084–16096 | 16085
View Article Online
Published on 20 August 2014. Downloaded by Michigan Technological University on 22/10/2014 05:08:52.
Paper
Fig. 1 Thermal ellipsoid plot of (iPr2POCNiPr2)PdCl (2a). All the hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)–C(1), 1.956(2); Pd(1)–P(1), 2.1890(6); Pd(1)–N(1), 2.2204(17); Pd(1)–Cl(1), 2.3922(6). Selected bond angles (°): C(1)–Pd(1)–P(1), 80.35(7); C(1)– Pd(1)–N(1), 81.84(8); P(1)–Pd(1)–N(1), 162.10(5); C(1)–Pd(1)–Cl(1), 177.32(7); P(1)–Pd(1)–Cl(1), 97.04(2); N(1)–Pd(1)–Cl(1), 100.79(5).
89% yield. The 31P{1H} NMR spectrum of 2b shows a singlet at δ 204.9 ppm (cf. (tBu4POCOP)PdCl,18 δ 192.1 ppm). The complexes 2a and 2b were characterized well by 1H and 13C NMR spectroscopy as well as elemental analyses. Compounds 2a and 2b were further characterized by single X-ray crystallography (Fig. 1 and 2). For both compounds, the coordination geometry around palladium is distorted squareplanar. Selected bond lengths and bond angles are given in the respective figure captions. For 2a, the Pd–C(ipso) bond length is 1.956(2) Å, slightly shorter than the Pd–C bond length (1.974(±1) Å) of (iPr4POCOP)PdCl; whereas the Pd– Cl bond length (2.3922(6) Å) is slightly longer than the corresponding bond length (2.371(2) Å) of (iPr4POCOP)PdCl.16 This could be due to the σ-donor strength exerted by the (iPr2POCNiPr2) moiety upon the palladium in 2a being stronger
Fig. 2 Thermal ellipsoid plot of (tBu2POCNiPr2)PdCl (2b). All the hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)–C(1), 1.958(4); Pd(1)–P(1), 2.2090(11); Pd(1)–N(1), 2.229(3); Pd(1)–Cl(1), 2.3943(11). Selected bond angles (°): C(1)–Pd(1)–P(1), 80.56(12); C(1)– Pd(1)–N(1), 81.35(15); P(1)–Pd(1)–N(1), 161.65(9); C(1)–Pd(1)–Cl(1), 177.93(13); P(1)–Pd(1)–Cl(1), 99.18(4); N(1)–Pd(1)–Cl(1), 99.00(9).
16086 | Dalton Trans., 2014, 43, 16084–16096
Dalton Transactions
than that of the (iPr4POCOP) moiety in the (iPr4POCOP)PdCl complex. Interestingly, the Pd–P bond length (2.1890(6) Å) in 2a is significantly shorter than the corresponding Pd–P bond lengths (2.276(±2) and 2.284(±2) Å) reported for (iPr4POCOP)PdCl. The Pd–N bond length (2.2204(17) Å) in 2a is slightly longer than the Pd–N bond length (2.159(±2) Å) observed for a similar palladium complex, (3-MeO-Ph2POCNMe2)PdCl.14h The P–Pd–N bond angle (162.10(5)°) of 2a is slightly greater than that observed for (3-MeO-Ph2POCNMe2)PdCl (P–Pd–N, 159.53(5)°). The C–Pd–P bond angle (80.35(7)°) of 2a is comparable with that observed for (iPr4POCOP)PdCl (C–Pd–P; 80.500(±2) and 79.920(±2)°). The C–Pd–N bond angle (81.84(8)°) is slightly greater than the C–Pd–P bond angle (80.35(7)°) for 2a. For compound 2b, two methyl groups (C15, C16 and C20, C21) of each tert-butyl group showed large anisotropic displacement parameters (ADP) due to orientational disorder. The Pd– C(ipso) and Pd–Cl bond lengths in 2b are 1.958(4) and 2.3943(11) Å, respectively; which are comparable with the corresponding bond lengths in 2a. The Pd–P bond length (2.2090(11) Å) in 2b is slightly longer than the Pd–P bond length of 2a, whereas the Pd–N bond length (2.229(3) Å) in 2b is comparable with that observed for 2a. The P–Pd–N (161.65(9)°), C–Pd–P (80.56(12)°) and C–Pd–N (81.35(15)°) bond angles of 2b are comparable with the corresponding bond angles in 2a. Catalytic activity of (R2POCNiPr2)PdCl complexes for the C–H bond arylation of azoles The newly developed hybrid pincer complexes, (iPr2POCNiPr2) PdCl (2a) and (tBu2POCNiPr2)PdCl (2b), were optimized and employed for the direct C–H bond arylation of azoles with aryl iodides. Initially, the complex 2a was screened for the C–H bond arylation of benzothiazole (6a, 0.50 mmol) with 4-iodotoluene (7a, 0.75 mmol) as the electrophile, employing CuI as a co-catalyst. After investigating various reaction parameters, we found that the coupled product 2-( p-tolyl)benzothiazole (8aa) could be obtained in 97% isolated yield by employing 0.5 mol% of catalyst 2a and 5.0 mol% of CuI, in the presence of Cs2CO3 (0.75 mmol) in DMF.19 Other carbonate bases like Na2CO3 and K2CO3, as well as a cesium source like CsOAc, were found to be less effective (5–34%). The use of a K3PO4 base also gave a good yield (88%) of 8aa. The polar aprotic solvent DMF was found to be the solvent of choice,20 whereas solvents like dioxane and toluene led to diminished yields. The presence of CuI as a co-catalyst was very much essential for obtaining a good conversion rate. Direct arylation proceeded even in the absence of a CuI co-catalyst, however with low efficacy (21% of 8aa and a TON of 42). The CuI most likely enhances the transmetallation of the azoles to the palladium center.8l The presence of the palladium catalyst 2a under the standard conditions (6a, 0.50 mmol; 7a, 0.75 mmol; Cs2CO3, 0.75 mmol; CuI, 5 mol% in DMF at 120 °C) was necessary; in its absence the arylation product 8aa formed in
Published on 20 August 2014. Downloaded by Michigan Technological University on 22/10/2014 05:08:52.
PAPER
Cite this: Dalton Trans., 2014, 43, 16084
View Journal | View Issue
Design and development of POCN-pincer palladium catalysts for C–H bond arylation of azoles with aryl iodides† Shrikant M. Khake,a Vineeta Soni,a Rajesh G. Gonnadeb and Benudhar Punji*a Well-defined and efficient POCN-ligated palladium complexes have been developed for the direct C–H bond arylation of azoles with aryl iodides. The phosphinite-amine pincer ligands 1-(R2PO)-C6H4-3(CH2NiPr2) [R2POCNiPr2-H; R = iPr (1a), R = tBu (1b)] and corresponding palladium complexes {2-(R2PO)C6H3-6-(CH2NiPr2)}PdCl [(R2POCNiPr2)PdCl; R = iPr (2a), R = tBu (2b)] were synthesized in good yields. Treatment of palladium complex 2a with KI and AgOAc afforded the complexes (iPr2POCNiPr2)PdI (3a) and (iPr2POCNiPr2)Pd(OAc) (4a), respectively. Similarly, the reaction of 2a with benzothiazolyl-lithium produces the (iPr2POCNiPr2)Pd(benzothiazolyl) (5a) complex in a quantitative yield. The pincer palladium complex 2a efficiently catalyzes the C–H bond arylation of benzothiazole, substituted-benzoxazoles and 5-aryl oxazoles with diverse aryl iodides in the presence of CuI as a co-catalyst under mild reaction conditions. This represents the first example of a pincer palladium complex being applied for the direct
Received 26th May 2014, Accepted 19th August 2014
C–H bond arylation of any heterocycle with low catalyst loading. A preliminary mechanistic investigation
DOI: 10.1039/c4dt01547a
reveals that palladium nanoparticles are presumably not the catalytically active form of 2a and supports the direct involvement of the catalyst 2a, with complex 5a being a probable key intermediate in the cata-
www.rsc.org/dalton
lytic reaction.
Introduction Direct C–H bond functionalization of heteroarenes has raised much interest as an alternative to traditional cross-coupling reactions, because such a process bypasses pre-activation steps such as the halogenation or metallation of heteroarenes.1 The transition metal-catalyzed C–H bond functionalizations, like arylation, alkenylation, alkynylation and alkylation, of various heteroarenes have been widely explored over the last few years.2 Most importantly, the arylation of azoles has received particular attention, as arylated azoles are essential building blocks of diverse biological and pharmaceutical compounds.3 The C-2 arylations of azoles to synthesize 2-arylated azoles have been
a Organometallic Synthesis and Catalysis Group, Chemical Engineering Division, CSIR–National Chemical Laboratory (CSIR–NCL), Dr. Homi Bhabha Road, Pune – 411 008, Maharashtra, India. E-mail: [email protected]; Fax: +91-20-25902621; Tel: +91-20-2590 2733 b Centre for Material Characterization, CSIR–National Chemical Laboratory (CSIR–NCL), Dr. Homi Bhabha Road, Pune – 411 008, Maharashtra, India † Electronic supplementary information (ESI) available: Details of the experimental data and NMR spectra of all compounds, crystal structure data of complexes 2a and 2b, and the 31P{1H} NMR spectrum of the (iPr2POCNiPr2)Pd species during the arylation of azole, demonstrating the catalyst resting state. CCDC 973533 and 973534. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4dt01547a
16084 | Dalton Trans., 2014, 43, 16084–16096
realized by the employment of various transition metal salts with suitable ligand sets.4 Among them, the most convenient and inexpensive transition metal catalysts, such as complexes of nickel5 and copper,6 represent a very important development for the arylation of azoles in terms of the catalyst cost for large scale synthesis. However, in most cases the utilization of strong bases and harsh reaction conditions limits the further advancement of those methodologies. The arylation of azoles has also been reported under mild conditions employing precious metal catalysts, like Ru,2j Rh,7 or Pd,8 where high loading of the catalyst (>5 mol%) is essential for the completion of reactions. Moreover, many of these catalysts were generated in situ (not “welldefined”) with few exceptions;8l hence limiting the proper understanding of the catalyst’s reactivity and reaction system. Although many of these in situ generated catalysts are convenient for the arylation of various azoles, there is still a demand to develop well-defined catalyst which can execute the same tasks with minimal catalyst loading. Herein, our objective is to develop well-designed, well-characterized and competent palladium catalysts for the direct C–H bond arylation of azoles, as in many cases such catalysts are more efficient than the transformations carried out by metal salts and added ligands. Pincer-ligated transition metal catalysts have shown exceptionally high thermal stability and catalytic activity for various important organic transformations in comparison with the tra-
This journal is © The Royal Society of Chemistry 2014
View Article Online
Published on 20 August 2014. Downloaded by Michigan Technological University on 22/10/2014 05:08:52.
Dalton Transactions
Chart 1
Paper
General representation of pincer palladium complexes.
ditional mono- or bi-dentate ligated transition metal catalysts; as the tight tridentate coordination in the pincer system keeps the metal and ligand together in each catalytic step, where the ligand effects are conveniently transferred to the metal center (Chart 1).9 For example, the PCP pincer palladium complexes, [{2,6-(iPr2PCH2)2-C6H3}Pd(OCOCF3)] and [{2,6-(iPr2PCH2)2-3,5(CH3)2-1-CH2-C6H}Pd(OCOCF3)], are highly active catalysts for the Heck coupling reaction with bromo- and iodo-arene electrophiles;10 whereas a phosphinite-based POCOP pincer palladium catalyst, [{2,6-(iPr2PO)2-C6H3}PdCl], shows efficient activity for the coupling of styrene with relatively difficult aryl chloride electrophiles.11 Similarly, aminophosphine-based pincer palladium complexes, [{2,6-(EP(piperidinyl)2)2-C6H3}PdCl] (E = NH, O), and an adamantyl core palladium complex, [{2,6(Cy2PCH2)2-C10H13}PdCl], are extremely efficient catalysts for Suzuki cross-coupling reactions.12 Driven by the high thermal stability and extraordinary catalytic efficiency of pincer palladium complexes for the Suzuki and Heck coupling reactions, we became fascinated in developing a novel pincer palladium catalyst for C–C bond forming reactions via direct C–H bond functionalization. As many of these pincer palladium catalysts are assumed to follow a Pd(II)–Pd(IV)–Pd(II) catalytic pathway during cross-coupling reactions,12b a pincer-ligated palladium complex with a strong σ-donor atom on the ligand would enhance the electrophilic oxidative addition at the Pd(II) center and stabilize the Pd(IV) species.13 Furthermore, transmetallation and electrophilic attack have opposing electron demands during such catalysis. Hence, we envisioned that an amino-phosphinite ligand,14 where the electron-rich hard donor amino side and phosphinite segment would assist in electrophilic addition and transmetallation, respectively, could be an ideal system to stabilize the catalytically active palladium species in the higher oxidation state,15 which can lead to a high conversion rate with low catalyst loading. With these hypotheses, herein, we have synthesized a “hybrid” pincer palladium catalyst system which efficiently catalyzes the arylation of various azoles with aryl iodides with low catalyst loading in the presence of CuI as a cocatalyst. The preliminary mechanistic investigation has been carried out to gain an insight into the catalyst’s behaviour and reaction pathway.
bromide (Scheme 1). First, 3-hydroxy benzyl bromide was treated with two equivalents of diisopropyl amine in acetone to obtain the colorless product of 3-((diisopropylamino)methyl)phenol in 82% isolated yield. This compound was characterized by 1H and 13C NMR spectroscopy as well as HRMS. The treatment of 3-((diisopropylamino)methyl)phenol with NaH, followed by reaction with dialkylchlorophosphine, R2PCl (R = iPr, tBu) produced the ligands {1-(R2PO)-C6H4-3(CH2NiPr2)}, R2POCNiPr2-H (R = iPr, 1a; R = tBu, 1b), as colorless viscous liquids in excellent yields. The 31P{1H} NMR spectrum of 1a displayed a peak at 148.8 ppm (for the O-PiPr2 moiety), whereas that of 1b displayed a peak at 154.3 ppm (for the O-PtBu2 moiety). These NMR values of 1a and 1b are consistent with the 31P NMR data reported for similar compounds i.e. iPr4POCOP-H16 (δ 149.0 ppm) and tBu4POCOP-H17 (δ 153.1 ppm), respectively. These crude viscous liquids were used for the metallation reactions without further purification. The metallation of the ligand iPr2POCNiPr2-H with Pd(COD)Cl2 in the presence of K3PO4 in 1,4-dioxane under refluxing conditions gave {2-(iPr2PO)-C6H3-6-(CH2NiPr2)}PdCl, (iPr2POCNiPr2)PdCl (2a), as an air-stable light yellow solid. The 31P{1H} NMR spectrum of 2a shows a singlet at δ 198.9 ppm (cf. (iPr4POCOP)PdCl,16 δ 187.7 ppm). The 1H NMR spectrum of compound 2a shows signals for only three protons in the aromatic region, with the disappearance of the signal corresponding to the apical proton, which clearly indicates the formation of the pincer palladium complex. Similarly, the complexation of tBu2 POCNiPr2-H with Pd(COD)Cl2 in the presence of K3PO4 in toluene under refluxing conditions produced {2-(tBu2PO)-C6H36-(CH2NiPr2)}PdCl, (tBu2POCNiPr2)PdCl (2b), as a yellow solid in
Results and discussion Synthesis of the POCN-H ligands and palladium complexes The R2POCNiPr2-H {1-(R2PO)-C6H4-3-(CH2NiPr2)} ligands were synthesized in two steps starting from 3-hydroxy benzyl
This journal is © The Royal Society of Chemistry 2014
Scheme 1 Synthesis of the (R2POCNiPr2)-H ligands and (R2POCNiPr2) PdCl complexes.
Dalton Trans., 2014, 43, 16084–16096 | 16085
View Article Online
Published on 20 August 2014. Downloaded by Michigan Technological University on 22/10/2014 05:08:52.
Paper
Fig. 1 Thermal ellipsoid plot of (iPr2POCNiPr2)PdCl (2a). All the hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)–C(1), 1.956(2); Pd(1)–P(1), 2.1890(6); Pd(1)–N(1), 2.2204(17); Pd(1)–Cl(1), 2.3922(6). Selected bond angles (°): C(1)–Pd(1)–P(1), 80.35(7); C(1)– Pd(1)–N(1), 81.84(8); P(1)–Pd(1)–N(1), 162.10(5); C(1)–Pd(1)–Cl(1), 177.32(7); P(1)–Pd(1)–Cl(1), 97.04(2); N(1)–Pd(1)–Cl(1), 100.79(5).
89% yield. The 31P{1H} NMR spectrum of 2b shows a singlet at δ 204.9 ppm (cf. (tBu4POCOP)PdCl,18 δ 192.1 ppm). The complexes 2a and 2b were characterized well by 1H and 13C NMR spectroscopy as well as elemental analyses. Compounds 2a and 2b were further characterized by single X-ray crystallography (Fig. 1 and 2). For both compounds, the coordination geometry around palladium is distorted squareplanar. Selected bond lengths and bond angles are given in the respective figure captions. For 2a, the Pd–C(ipso) bond length is 1.956(2) Å, slightly shorter than the Pd–C bond length (1.974(±1) Å) of (iPr4POCOP)PdCl; whereas the Pd– Cl bond length (2.3922(6) Å) is slightly longer than the corresponding bond length (2.371(2) Å) of (iPr4POCOP)PdCl.16 This could be due to the σ-donor strength exerted by the (iPr2POCNiPr2) moiety upon the palladium in 2a being stronger
Fig. 2 Thermal ellipsoid plot of (tBu2POCNiPr2)PdCl (2b). All the hydrogen atoms are omitted for clarity. Selected bond lengths (Å): Pd(1)–C(1), 1.958(4); Pd(1)–P(1), 2.2090(11); Pd(1)–N(1), 2.229(3); Pd(1)–Cl(1), 2.3943(11). Selected bond angles (°): C(1)–Pd(1)–P(1), 80.56(12); C(1)– Pd(1)–N(1), 81.35(15); P(1)–Pd(1)–N(1), 161.65(9); C(1)–Pd(1)–Cl(1), 177.93(13); P(1)–Pd(1)–Cl(1), 99.18(4); N(1)–Pd(1)–Cl(1), 99.00(9).
16086 | Dalton Trans., 2014, 43, 16084–16096
Dalton Transactions
than that of the (iPr4POCOP) moiety in the (iPr4POCOP)PdCl complex. Interestingly, the Pd–P bond length (2.1890(6) Å) in 2a is significantly shorter than the corresponding Pd–P bond lengths (2.276(±2) and 2.284(±2) Å) reported for (iPr4POCOP)PdCl. The Pd–N bond length (2.2204(17) Å) in 2a is slightly longer than the Pd–N bond length (2.159(±2) Å) observed for a similar palladium complex, (3-MeO-Ph2POCNMe2)PdCl.14h The P–Pd–N bond angle (162.10(5)°) of 2a is slightly greater than that observed for (3-MeO-Ph2POCNMe2)PdCl (P–Pd–N, 159.53(5)°). The C–Pd–P bond angle (80.35(7)°) of 2a is comparable with that observed for (iPr4POCOP)PdCl (C–Pd–P; 80.500(±2) and 79.920(±2)°). The C–Pd–N bond angle (81.84(8)°) is slightly greater than the C–Pd–P bond angle (80.35(7)°) for 2a. For compound 2b, two methyl groups (C15, C16 and C20, C21) of each tert-butyl group showed large anisotropic displacement parameters (ADP) due to orientational disorder. The Pd– C(ipso) and Pd–Cl bond lengths in 2b are 1.958(4) and 2.3943(11) Å, respectively; which are comparable with the corresponding bond lengths in 2a. The Pd–P bond length (2.2090(11) Å) in 2b is slightly longer than the Pd–P bond length of 2a, whereas the Pd–N bond length (2.229(3) Å) in 2b is comparable with that observed for 2a. The P–Pd–N (161.65(9)°), C–Pd–P (80.56(12)°) and C–Pd–N (81.35(15)°) bond angles of 2b are comparable with the corresponding bond angles in 2a. Catalytic activity of (R2POCNiPr2)PdCl complexes for the C–H bond arylation of azoles The newly developed hybrid pincer complexes, (iPr2POCNiPr2) PdCl (2a) and (tBu2POCNiPr2)PdCl (2b), were optimized and employed for the direct C–H bond arylation of azoles with aryl iodides. Initially, the complex 2a was screened for the C–H bond arylation of benzothiazole (6a, 0.50 mmol) with 4-iodotoluene (7a, 0.75 mmol) as the electrophile, employing CuI as a co-catalyst. After investigating various reaction parameters, we found that the coupled product 2-( p-tolyl)benzothiazole (8aa) could be obtained in 97% isolated yield by employing 0.5 mol% of catalyst 2a and 5.0 mol% of CuI, in the presence of Cs2CO3 (0.75 mmol) in DMF.19 Other carbonate bases like Na2CO3 and K2CO3, as well as a cesium source like CsOAc, were found to be less effective (5–34%). The use of a K3PO4 base also gave a good yield (88%) of 8aa. The polar aprotic solvent DMF was found to be the solvent of choice,20 whereas solvents like dioxane and toluene led to diminished yields. The presence of CuI as a co-catalyst was very much essential for obtaining a good conversion rate. Direct arylation proceeded even in the absence of a CuI co-catalyst, however with low efficacy (21% of 8aa and a TON of 42). The CuI most likely enhances the transmetallation of the azoles to the palladium center.8l The presence of the palladium catalyst 2a under the standard conditions (6a, 0.50 mmol; 7a, 0.75 mmol; Cs2CO3, 0.75 mmol; CuI, 5 mol% in DMF at 120 °C) was necessary; in its absence the arylation product 8aa formed in
