[Pd(IPr*)(acac)Cl]: An Easily Synthesized, Bulky Precatalyst for C–N

Article pubs.acs.org/Organometallics

[Pd(IPr*)(acac)Cl]: An Easily Synthesized, Bulky Precatalyst for C−N Bond Formation Sebastien Meiries, Anthony Chartoire, Alexandra M. Z. Slawin, and Steven P. Nolan* EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews KY16 9ST, U.K. S Supporting Information *

ABSTRACT: A very straightforward synthesis of [Pd(IPr*)(acac)Cl] has been developed from commercially available Pd(acac)2 and the easily prepared IPr*·HCl (acac = acetylacetonate; IPr* = N,N′-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene). The reactivity of the resulting complex [Pd(IPr*)(acac)Cl] (1) as a highly active PdII precatalyst for the Buchwald−Hartwig arylamination coupling has been explored. A wide range of substrates with varying electronic and steric demands of both coupling partners has been screened successfully. The chemoselectivity of the reaction was also explored by using aryl heterodihalides.

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INTRODUCTION Palladium-catalyzed arylamination has become an important and widely employed method for the formation of C−N bonds.1 In comparison to reports of phosphine-based ligands2 commonly used for this reaction, considerably fewer studies have appeared using N-heterocyclic carbene (NHC) based ligands.1d,3 However, unlike their phosphine analogues, Pd-NHC complexes are now well-known for their significant air and moisture stability, which renders them very user friendly. Their catalytic activity for the oxidative addition of aryl halides is related to their strong σdonating properties.4 Their steric hindrance also facilitates reductive elimination and presumably helps stabilize the Pdcentered 12-electron reactive intermediate.5 Sterically demanding ancillary ligands can kinetically stabilize highly reactive low-valent transition metals and permit high catalytic activity.6 Spectacular reactivity was attributed to a “flexible steric bulk” in which the ligands can adjust toward incoming substrates, while enabling the stabilization of a low-valent active intermediate.7 Similarly, bulky NHCs, in which the carbene center sits in the middle of a large bowl-shaped cavity, have also provided interesting results.8 In this context, the bulky precatalyst [Pd(IPr)(acac)Cl] developed by Nolan et al.3m proved to be very efficient for the catalytic Buchwald−Hartwig arylamination reaction. In an effort to test whether more sterically demanding ligands would lead to improved catalytic performance, the preparation of the bulkier [Pd(IPr*)(acac)Cl] and a subsequent study of its catalytic reactivity in arylamination is reported here.

of the IPr* ligand onto palladium was achieved through a facile ligand exchange between IPr*·HCl and Pd(acac)2 as described in the literature3m and afforded [Pd(IPr*)(acac)Cl] (1) as a well-defined compound (Scheme 1). Compound 1 proved to be both air- and moisture-stable, and suitable crystals for X-ray diffraction were successfully grown by slow diffusion of hexane into a saturated C6D6 solution of the complex (Figure 1).10 The Pd1−C1 bond length is longer than in the case of the [Pd(IPr)(acac)Cl] analogue3q (2.019(10) Å for 1 and 1.9694(17) Å for [Pd(IPr)(acac)Cl]). This presumably is due to the high steric hindrance brought about by the IPr* ligand. On the other hand, the Pd−O and Pd−Cl bond lengths are quite similar to those for the [Pd(IPr)(acac)Cl] complex. The structure of 1 adopts a slightly distorted square planar geometry. Finally, the percent buried volume of IPr* in the Pd system was calculated using the web application SambVca.11 Unsurprisingly, with a percent buried volume of 42.2%,12 IPr* was found to be larger than IPr (%VBur = 34.7%)13 in the [Pd(NHC)(acac)Cl] motif. The catalytic properties of 1 in Buchwald−Hartwig arylamination were explored by screening several base/solvent systems (Table 1). The results gave preliminary guidelines showing that several bases (NaOtBu, KOH, NaOH, Cs2CO3, K3PO4) were inefficient for the coupling. The nature of the solvent proved to have a minor effect on the conversion of the reaction but was important for the complete dissolution of both precatalyst 1 and the base. Comparable efficiencies were obtained with potassium tert-amylate, potassium tert-butoxide,

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RESULTS AND DISCUSSION Multigram quantities of IPr*·HCl were successfully prepared as described by Markó et al. (Scheme 1).9 Ultimately, the binding © 2012 American Chemical Society

Received: March 13, 2012 Published: March 26, 2012 3402

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Scheme 1. Synthesis of [Pd(IPr*)(acac)Cl]

shown in Table 2. These preliminary data clearly demonstrated that the catalytic arylamination displayed the best efficiency with the system LiHMDS/1,4-dioxane14 (entries 3, 6, 9, and 12) and further studies were conducted with this optimized system (Tables 3 and 4). The catalyst loading, the reaction time, and the temperature of the reaction were thoroughly screened by using a combination of sterically and electronically demanding substrates. A first set of reactions was conducted with 1.0 mol % catalyst 1 at room temperature (Table 3), allowing for the coupling to proceed with great efficiency in short reaction times.15 Under these conditions, the couplings of hindered substrates (entries 1 and 5), deactivated aryl halides (entries 3 and 6), and heterocyclic halides (entries 2 and 4) were successfully achieved. However, less reactive and more hindered substrates gave only modest conversions after 18 h using these particular conditions. A simple increase in temperature had a dramatic effect on the efficiency of the amination, permitting the coupling of more challenging substrates that failed under milder conditions (Table 4). More rapid conversions16 and good to excellent isolated yields were obtained for various substrates at lower catalyst loadings. A first scope was conducted at 50 °C (Table 4) and enabled us to highlight the excellent catalytic activity of 1 for the coupling of reasonably challenging bromides (entries 1−3). However, at the same temperature, aryl chlorides (entries 6−8) required higher catalyst loading (1.0 mol %) to be successfully coupled. Although lower catalyst loadings and lower temperatures could be successfully used with various coupling partners, the selected optimized conditions (0.4 mol % of catalyst loading at 110 °C in 1,4-dioxane) were generally applied to a wide number of substrates (Table 5). Hindered aryl halides (entries 4, 6, and 8) and amines (entries 3, 5, 6, 8, and 10) were successfully coupled under these conditions. Heterocyclic (entries 9 and 10), electron-rich (entries 7 and 8), and electron-deficient (entries 11 and 12) aryl halides also proved to be suitable partners. The demonstrated reactivity is on par with that of Pd-PEPPSI-IPent3j,17 catalyst. An important example is the good isolated yield obtained for the challenging coupling of both sterically and electronically disfavored 2-chloro-5-methoxy-1,3-dimethylbenzene with the very hindered 2,6-diisopropylaniline under these conditions (Table 5, entry 8). However, it is to be noted that methyl halobenzoates failed to couple with amines, as the undesired amidation reaction first occurred. The Buchwald−Hartwig arylamination is a very powerful synthetic tool for the preparation of a wide range of biologically active molecules.18 However, its synthetic applications could be significantly increased if the reaction could be applied in a completely chemoselective manner. This aspect is underexplored in the literature,3a,19 and therefore we proposed examining the reactivity of several aryl groups bearing heterodihalides (Table 6). Excellent selectivities were obtained

Figure 1. Molecular structure of 1. Hydrogens have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd1−C1, 2.019(10); Pd1−O73, 2.043(7); Pd1−O75, 2.063(7); Pd1−Cl1, 2.282(3); C1−Pd1−O73, 92.2(3); O73−Pd1−O75, 92.9(3); C1− Pd1−Cl1, 88.2(3); O75−Pd1−Cl1, 86.7(2).

and lithium bis(trimethylsilyl)amide, depending on the solvent used (Table 1, entries 1, 4, and 9). Table 1. First Screening of Base/Solvent System for Amination with [Pd(IPr*)(acac)Cl]a

entry 1 2 3 4 5 6 7 8 9

solvent toluene dimethoxyethane 1,4-dioxane toluene dimethoxyethane 1,4-dioxane toluene dimethoxyethane 1,4-dioxane

base t

KO Am KOtAm KOtAm KOtBu KOtBu KOtBu LiHMDS LiHMDS LiHMDS

GC conversn (%)b 37 5 10 45 5 17 21 34 37

a

Reagents and conditions: 4-chloroanisole (0.50 mmol), morpholine (0.55 mmol), Pd precatalyst 1 (0.50 mol %), solvent (0.5 mL), base (0.55 mmol), room temperature, 24 h. bConversion to coupling product based on starting aryl halide determined by GC.

To further determine the optimal base/solvent system, each set of conditions (Table 1, entries 1, 4, and 9) was used in the coupling of other challenging aryl halides with N-morpholine, as 3403

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Table 2. Further Screening toward Optimized Conditionsa

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Table 3. Arylamination Reactions at Room Temperaturea

CONCLUSION The utility of [Pd(IPr*)(acac)Cl] (1) as an easily synthesized and well-defined precatalyst has been highlighted for the arylamination of various substrates. Beyond its air and moisture stability and its easy preparation,20 this very bulky NHCbearing precatalyst can be efficiently used for the coupling of sterically and electronically challenging substrates with useful chemoselectivity when heterodihalides are employed. In some cases, [Pd(IPr*)(acac)Cl] (1) appears to have catalytic activity similar to that of its earlier generation [Pd(IPr)(acac)Cl] congener.21 Nevertheless, it was also successfully employed for a much wider range of coupling substrates at lower catalyst loadings or lower temperatures.

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EXPERIMENTAL SECTION

All aryl halides and amines were used as purchased, except for 2chloro-5-methoxy-1,3-dimethylbenzene (Table 5, entry 8), which was prepared by methylation of the corresponding 4-chloro-3,5-dimethylphenol. Anhydrous 1,4-dioxane and toluene and the bases (NaOtBu, KOtBu, Na2CO3, K3PO4, Cs2CO3, K2CO3, NaOH, KOH) were used as received and stored in a glovebox. 1,2-Dimethoxyethane (DME) was distilled on sodium/benzophenone, degassed, and stored in a glovebox. Pd(acac)2 was purchased from UMICORE and stored under atmospheric conditions. Flash column chromatography was performed on silica gel with 60 Å pore diameter and 40−63 μm particle size. 1H and 13C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker 400 or 300 MHz spectrometer at ambient temperature in CDCl3 without TMSCl as internal standard. NMR peaks were assigned by using COSY and HSQC experiments, except in the case of [Pd(IPr*)(acac)Cl] (1), where an HMBC experiment was necessary. Elemental analyses were performed at London Metropolitan University, 166−220 Holloway Road, London N7 8DB, U.K. Highresolution mass spectrometry was performed by the EPSRC National Mass Spectrometry Service Centre (NMSSC), Grove Building Extn., Swansea University, Singleton Park, Swansea SA2 8PP, U.K. Procedure for the Synthesis of [Pd(IPr*)(acac)Cl] (1). In a Schlenk flask equipped with a magnetic stirring bar were added IPr*·HCl (950 mg, 1.00 mmol) and Pd(acac)2 (225 mg, 0.74 mmol) in dry 1,4-dioxane (15 mL) under an atmosphere of nitrogen. The reaction mixture was then refluxed for 24 h. This time has not yet been optimized. After this time, dioxane was evaporated, the crude product was dissolved in DCM, the solution was filtered on a pad of silica covered with Celite, and the pad was eluted with DCM. After

a

Reagents and conditions: aryl halide (0.50 mmol), amine (0.55 mmol), Pd precatalyst 1 (1.0 mol %), 1,4-dioxane (0.5 mL), LiHMDS (0.55 mmol), room temperature. bIsolated yield after chromatography on silica gel; average of two runs. cReaction time of 3 h. dReaction time of 18 h. eChloronaphtalene was purchased and used as a mixture of 1- and 2-isomers and resulted in the isolation of the corresponding cross-product as a separable 9.6:1 mixture of isomers that were fully characterized.

for the coupling of chloroiodo (entry 1) and bromochloro aryls (entries 2−6) with diverse amines. In each case only a single adduct was detected with excellent GC conversions and isolated with good to excellent yields. Surprisingly, no coupling was observed between p-bromoiodobenzene and 2,6-dimethylaniline. Other substrates such as 2,3- and 2,4dichlorotoluenes were also subjected to the same conditions to determine the influence of the methyl group on the selectivity of the reaction. Although couplings occurred at both positions with some encouraging selectivities, inseparable mixtures of isomers were obtained. 3404

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Table 4. Arylamination Screening of Various Substrates with 0.2−1.0 mol % of [Pd(IPr*)(acac)Cl] at 50 °Ca

a Reagents and conditions: aryl halide (0.50 mmol), amine (0.55 mmol), 1,4-dioxane (0.5 mL), LiHMDS (0.55 mmol), 50 °C. bIsolated yield after chromatography on silica gel; average of two runs. cReaction time of 3 h. dReaction time of 18 h. eReaction time of 43 h.

17.6 (CH3), 18.2 (2 × CH3), 111.7 (CHAr), 118.1 (CHAr), 122.3 (CIVAr), 125.5 (CHAr), 126.9 (CHAr), 128.5 (CHAr), 130.2 (CHAr), 135.5 (CIVAr), 138.7 (CIVAr), 144.1 (CIVAr). N-Methyl-N-phenylpyridin-2-amine (Table 3, Entries 2 and 4; Table 4, Entries 4 and 5). The general procedure yielded the pure arylamine as a yellow oil. Data were in full agreement with those reported in the literature.2,23 1H NMR (400 MHz, CDCl3): δ 3.49 (3H, s, CH3), 6.54 (1H, dt, J = 8.7, 0.8 Hz, CHpyr), 6.59 (1H, ddd, J = 6.9, 4.9, 0.8 Hz, CHpyr), 7.17−7.30 (4H, m, CHpyr + CHAr), 7.35−7.41 (2H, m, CHAr), 8.26 (1H, ddd, J = 5.1, 2.1, 1.0 Hz, 3-CHpyr). 13C{1H} NMR (100 MHz, CDCl3): δ 38.1 (N−CH3), 108.9 (CHpyr), 112.9 (CHpyr), 125.1 (CHAr), 126.0 (CHAr), 129.4 (CHAr), 136.3 (CHpyr), 146.6 (CIVAr), 147.6 (CHpyr), 158.6 (2-CIVpyr). 4-(4-Methoxyphenyl)morpholine (Table 3, Entries 3 and 6; Table 4, Entry 3; Table 5, Entry 7). The general procedure yielded the pure arylamine as a white solid. Data were in full agreement with those reported in the literature.3j,24 1H NMR (400 MHz, CDCl3): δ 3.01 (4H, m, 2 × N−CH2), 3.74 (3H, s, O−CH3), 3.82 (4H, m, 2 × O− CH2), 6.86 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 50.3 (2 × N−CH2), 55.0 (O−CH3), 66.6 (2 × O−CH2), 114.0 (CHAr), 117.3 (CHAr), 145.3 (N−CIVAr), 153.5 (O−CIVAr). 4-(Naphthalen-1-yl)morpholine (Table 3, Entry 5). The general procedure yielded the pure arylamine as a separable mixture of two isomers (154 mg, 72% and 16 mg, 8%) as white and pinkish solids, respectively. Data were in full agreement with those reported in the literature for both isomers.24a,25 1H NMR (400 MHz, CDCl3): δ 3.15 (4H, app t, J = 4.6 Hz, 2 × N−CH2), 4.03 (4H, app t, J = 4.6 Hz, 2 × O−CH2), 7.13 (1H, dd, J = 7.4, 0.8 Hz, 2-CHAr), 7.47 (1H, app t, J = 8.2 and 7.4 Hz, 3-CHAr), 7.50−7.59 (2H, m, 7-CHAr + 8-CHAr), 7.64 (1H, d, J = 8.2 Hz, 4-CHAr), 7.90 (1H, m, 6-CHAr), 8.30 (1H, m, 9CHAr). 13C{1H} NMR (100 MHz, CDCl3): δ 53.4 (2 × N−CH2), 67.3 (2 × O−CH2), 114.6 (CHAr), 123.3 (CHAr), 123.7 (CHAr), 125.4 (CHAr), 125.8 (CHAr), 128.4 (CHAr), 128.7 (CIVAr), 134.7 (CIVAr), 149.3 (N−CIVAr). 4-(Naphthalen-2-yl)morpholine (Table 3, Entry 5). 1H NMR (400 MHz, CDCl3): δ 3.28 (4H, app t, J = 4.8 Hz, 2 × N−CH2), 3.93 (4H, app t, J = 4.8 Hz, 2 × O−CH2), 7.14 (1H, d, J = 2.6 Hz, 2-CHAr), 7.27

evaporation of the solvents, the complex was triturated with pentane, and then the supernatant was decanted. After drying under high vacuum, the pure complex was obtained as a yellow powder (811 mg, 95%). 1H NMR (400 MHz, CDCl3): δ 7.26−7.00 (m, 32H, HAr), 6.84−6.69 (m, 12H, HAr), 5.87 (s, 4H, CH), 5.10 (s, 1H, CHacac), 4.93 (s, 2H, CHIm), 2.24 (s, 6H, CH3), 2.06 (s, 3H, CH3acac), 0.72 (s, 3H, CH3acac). 13C{1H} NMR (100 MHz, CDCl3): δ 186.9 (C−Oacac), 185.5 (C−Oacac), 154.7 (NCN), 144.0 (CAr), 142.4 (CAr), 139.0 (CAr), 135.2 (CAr), 130.8 (CAr, b), 129.7 (CAr), 128.2 (CAr), 127.9 (CAr), 126.4 (CAr), 126.2 (CAr), 124.4 (CHIm), 100.3 (CHacac), 50.9 (CH), 27.3 (CH3acac), 26.3 (CH3acac), 21.8 (CH3). Anal. Calcd for C74H63ClN2O2Pd: C, 77.01; H, 5.50; N, 2.43. Found: C, 77.16; H, 5.41; N, 2.36. Buchwald−Hartwig Cross-Coupling of Aryl Halides with Primary and Secondary Amines: General Procedure. In a glovebox,22 a glass vial was charged with LiHMDS (0.55 mmol), equipped with a magnetic stir bar, and sealed with a screw cap fitted with a septum. The vial was then loaded with the neat amine (0.55 mmol) and the aryl halide (0.50 mmol) outside the glovebox. Finally, a premade solution of [Pd(IPr*)(acac)Cl] (1) in anhydrous solvent (prepared in a glovebox)22 was subsequently injected at room temperature under argon, and the reaction mixture was stirred until completion, as indicated by GC chromatography. After the reaction reached completion, the mixture was diluted with a minimum amount of dichloromethane and directly loaded onto silica gel to be purified by flash column chromatography (silica gel, diethyl ether in pentane). The reported yields are the results of two runs. In the case of solid starting materials, the solid was quickly added to the vial containing LiHMDS outside the glovebox and the vial was purged using classical Schlenk techniques. 2,6-Dimethyl-N-(o-tolyl)aniline (Table 3, Entry 1; Table 4, Entry 6; Table 5, entry 3). The general procedure yielded the pure arylamine as a white solid. Data were in full agreement with those reported in the literature.3m 1H NMR (400 MHz, CDCl3): δ 2.34 (6H, s, 2 × CH3), 2.48 (3H, s, CH3), 5.06 (1H, bs, NH), 6.32 (1H, dd, J = 7.6, 1.0 Hz, HAr), 6.86 (1H, td, J = 7.6, 1.0 Hz, HAr), 7.12 (1H, td, J = 8.0, 1.3 Hz, HAr), 6.20−6.30 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 3405

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Table 5. Arylamination using [Pd(IPr*)(acac)Cl] at 110 °Ca

Table 6. Chemoselective Arylamination of Various Dihalidesa

a

Reagents and conditions: aryl dihalide (0.50 mmol), amine (0.55 mmol), 1,4-dioxane (0.5 mL), LiHMDS (0.55 mmol), Pd precatalyst 1 (0.4 mol %), 110 °C. bIsolated yield after chromatography on silica gel, average of two runs. cReaction time of 3 h. dReaction time of 18 h. agreement with those reported in the literature.2q 1H NMR (400 MHz, CDCl3): δ 2.25 (6H, s, CH3), 3.31 (3H, s, N−CH3), 6.57 (2H, vbs, HAr), 6.82 (1H, app tt, J = 7.2, 1.0 Hz, HAr), 7.27−7.33 (5H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 17.9 (CH3), 36.9 (N− CH3), 110.8 (CHAr), 115.9 (CHAr), 126.8 (CHAr), 128.8 (CHAr), 129.1 (CHAr), 137.7 (Me-CIVAr), 144.0 (N−CIVAr), 148.0 (N−CIVAr). 4-(2-Methoxyphenyl)morpholine (Table 4, Entry 6). The general procedure yielded the pure arylamine as a colorless oil. Data were in full agreement with those reported in the literature.2 1H NMR (400 MHz, CDCl3): δ 3.08 (4H, m, 2 × N−CH2), 3.87 (3H, s, OCH3), 3.90 (4H, m, 2 × O−CH2), 6.87−6.90 (1H, m, HAr), 6.93−6.95 (2H, m, HAr), 7.00−7.06 (2H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 51.0 (N−CH2), 55.2 (CH3), 67.0 (O−CH2), 111.1 (CHAr), 117.8 (CHAr), 120.9 (CHAr), 123.0 (CHAr), 141.0 (O−CIVAr), 152.1 (N− CIVAr). 4-(p-Tolyl)morpholine (Table 5, Entries 2 and 13). The general procedure yielded the pure arylamine as a white solid. Data were in full agreement with those reported in the literature.7 1H NMR (400 MHz, CDCl3): δ 2.33 (3H, s, CH3), 3.15 (4H, m, 2 × N−CH2), 3.90 (4H, m, 2 × O−CH2), 6.87−6.90 (2H, m, HAr), 7.13−7.16 (2H, m, HAr). 13 C{1H} NMR (100 MHz, CDCl3): δ 20.3 (CH3), 49.8 (2 × N− CH2), 66.8 (2 × O−CH2), 115.9 (CHAr), 129.4 (Me-CIV), 129.6 (CHAr), 149.1 (N−CIVAr). Bis(2,6-dimethylphenyl)amine (Table 5, Entry 5). The general procedure yielded the pure arylamine as a white solid. Data were in full agreement with those reported in the literature.28 1H NMR (400 MHz, CDCl3): δ 2.11 (12H, s, 4 × CH3), 4.89 (1H, bs, NH), 6.94 (2H, dd, J = 6.8, 1.3 Hz, p-HAr), 7.08 (4H, app bd, J = 7.9 Hz, m-HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 19.1 (CH3), 121.7 (CHAr), 128.9 (CHAr), 129.5 (CIVAr), 141.7 (CIVAr). N-(2,6-Diisopropylphenyl)-2,6-dimethylaniline (Table 5, Entry 6). The general procedure yielded the pure arylamine as a colorless oil. Data were in full agreement with those reported in the literature.2,3c,10 1 H NMR (400 MHz, CDCl3): δ 1.26 (6H, s, 2 × CH3), 1.29 (6H, s, 2 × CH3), 2.13 (6H, s, 2 × CH3), 3.31 (2H, m, 2 × Me2CH), 4.95 (1H, bs, NH), 6.87 (1H, bt, J = 7.6 Hz, HAr), 7.09 (2H, bd, J = 7.7 Hz, HAr), 7.24−7.31 (3H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 19.3 (CH3), 23.4 (CH3), 28.0 (Me2CH), 119.6 (CHAr), 123.2 (CHAr),

a

Reagents and conditions: aryl halide (0.50 mmol), amine (0.55 mmol), Pd precatalyst 1 (0.4 mol %), 1,4-dioxane (0.5 mL), LiHMDS (0.55 mmol), 110 °C. bIsolated yield after chromatography on silica gel; average of two runs. cReaction time of 3 h. dReaction time of 18 h.

(1H, dd, J = 9.0, 2.6 Hz, 3-CHAr), 7.32 (1H, ddd, J = 7.9, 6.8, 1.4 Hz, 7-CHAr), 7.43 (1H, ddd, J = 8.2, 6.8, 1.4 Hz, 4-CHAr), 7.70−7.78 (3H, m, 6-CHAr). 13C{1H} NMR (100 MHz, CDCl3): δ 49.8 (2 × N− CH2), 66.9 (2 × O−CH2), 110.1 (CHAr), 118.9 (CHAr), 123.5 (CHAr), 126.3 (CHAr), 126.8 (CHAr), 127.4 (CHAr), 128.7 (CIVAr), 128.8 (CHAr), 134.5 (CIVAr), 149.1 (N−CIVAr). N-Methyl-N-phenylaniline (Tables 4 and 5, Entry 1). The general procedure yielded the pure arylamine as a yellowish oil. Data were in full agreement with those reported in the literature.26 1H NMR (400 MHz, CDCl3): δ 3.39 (3H, s, N−CH3), 7.01−7.06 (2H, m, HAr), 7.09−7.12 (4H, m, HAr), 7.32−7.39 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 40.2 (CH3), 120.4 (o-CHAr), 121.2 (p-CHAr), 129.1 (m-CHAr), 149.0 (N−CIVAr). 4-(2,6-Dimethylphenyl)morpholine (Table 4, Entry 2; Table 5, Entry 4). The general procedure yielded the pure arylamine as a white solid. Data were in full agreement with those reported in the literature.3c,d,g,27 1H NMR (400 MHz, CDCl3): δ 2.43 (6H, s, 2 × CH3), 3.16 (4H, app t, J = 4.6 Hz, 2 × N−CH2), 3.87 (4H, app t, J = 4.6 Hz, 2 × O−CH2), 7.02−7.09 (2H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 19.5 (CH3), 49.9 (2 × N−CH2), 68.0 (2 × O−CH2), 125.2 (CHAr), 128.9 (Me-CIV), 136.7 (CHAr), 147.7 (N−CIV). N-2,6-Trimethyl-N-phenylaniline (Table 4, Entry 5). The general procedure yielded the pure arylamine as a white solid. Data were in full 3406

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Organometallics

Article

124.8 (CHAr), 125.6 (CIVAr), 129.5 (CHAr), 138.8 (CIVAr), 143.1 (CIVAr), 144.1 (CIVAr). N-(2,6-Diisopropylphenyl)-4-methoxy-2,6-dimethylaniline (Table 5, Entry 8). The general procedure yielded the pure arylamine as an orange oil. 1H NMR (400 MHz, CDCl3): δ 1.18 (6H, s, 2 × CH3), 1.21 (6H, s, 2 × CH3), 2.09 (6H, s, 2 × CH3), 3.16 (2H, m, 2 × Me2CH), 3.83 (3H, s, OCH3), 4.72 (1H, bs, NH), 6.63 (2H, bs, J = 7.6 Hz, HAr), 7.09−7.19 (3H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 19.5 (CH3), 23.5 (CH3), 27.8 (Me2CH), 55.3 (OCH3), 114.4 (CHAr), 123.0 (CHAr), 123.4 (CHAr), 129.8 (Me-CIVAr), 136.5 (N−CIVAr), 139.7 (N−CIVAr), 141.5 (iPr−CIVAr), 153.9 (MeO-CIVAr). HRMS (ESI+): found m/z [M + H]+ 312.2325, calcd for C21H30ON 312.2322. N-Methyl-N-phenylpyridin-3-amine (Table 5, Entry 9). The general procedure yielded the pure arylamine as a yellowish oil. Data were in full agreement with those reported in the literature.10 1H NMR (400 MHz, CDCl3): δ 3.34 (6H, s, 2 × CH3), 7.05−7.11 (3H, m, m-CHAr + p-CHAr), 7.14 (1H, partially hidden dd, J = 8.5, 4.6 Hz, 4-CHpyr), 7.23 (1H, ddd, J = 8.5, 2.7, 1.4 Hz, 5-CHpyr), 7.30−7.37 (2H, m, o-CHAr), 8.15 (1H, dd, J = 4.6, 1.4 Hz, 6-CHpyr), 8.33 (1H, d, J = 2.7 Hz, 2-CHpyr). 13C{1H} NMR (100 MHz, CDCl3): δ 39.9 (N− CH3), 122.3 (m-CHAr), 123.2 (4-CHpyr), 123.4 (p-CHAr), 124.7 (5CHpyr), 129.5 (o-CHAr), 140.6 (2-CHpyr), 141.1 (6-CHpyr), 145.0 (N− CIVpyr), 147.8 (N−CIVAr). N-(2,6-Dimethylphenyl)pyridin-3-amine (Table 5, Entry 10). The general procedure yielded the pure arylamine as a white solid. 1H NMR (400 MHz, CDCl3): δ 2.21 (6H, s, 2 × CH3), 5.53 (1H, bs, NH), 6.65 (1H, ddd, J = 8.3, 2.7, 1.3 Hz, 5-CHpyr), 7.04 (1H, dd, J = 8.3, 4.8 Hz, 4-CHpyr), 7.13 (3H, m, CHAr), 8.00 (1H, dd, J = 4.8, 1.3 Hz, 6-CHpyr), 8.05 (1H, d, J = 2.7 Hz, 2-CHpyr). 13C{1H} NMR (100 MHz, CDCl3): δ 18.2 (CH3), 118.9 (5-CHpyr), 123.7 (4-CHpyr), 126.3 (CHAr), 128.6 (CHAr), 135.9 (Me-CIVAr), 136.5 (2-CHpyr), 136.8 (N− CIVpyr), 139.3 (6-CHpyr), 142.5 (N−CIVAr). 4-(Methyl(phenyl)amino)benzonitrile (Table 5, Entries 11 and 12). The general procedure yielded the pure arylamine as a brownish oil. Data were in full agreement with those reported in the literature.3a,2k,29 1 H NMR (400 MHz, CDCl3): δ 3.37 (3H, s, CH3), 6.73−6.77 (2H, m, HAr), 7.20−7.32 (3H, m, HAr), 7.40−7.48 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 39.9 (CH3), 99.0 (NC-CIVAr), 113.60 (CHAr), 120.1 (CN), 126.0 (CHAr), 126.2 (CHAr), 129.9 (CHAr), 133.0 (CHAr), 146.5 (N−CIVAr), 151.7 (N−CIVAr). N-(4-Chlorophenyl)-2′,6′-dimethylaniline (Table 6, Entries 1 and 4). The general procedure yielded the pure arylamine as a yellowish solid. Data were in full agreement with those reported in the literature.19 1H NMR (400 MHz, CDCl3): δ 2.25 (6H, s, 2 × CH3), 5.21 (1H, bs, NH), 6.45−6.50 (2H, m, HAr), 7.12−7.21 (5H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 18.2 (CH3), 114.5 (CHAr), 122.6 (Cl− CIVAr), 126.1 (CHAr), 128.6 (CHAr), 129.1 (CHAr), 135.9 (Me−CIVAr), 137.7 (N−CIVAr), 144.9 (N−CIVAr). 4-(4-Chlorophenyl)morpholine (Table 6, Entry 3). The general procedure yielded the pure arylamine as a white solid. Data were in full agreement with those reported in the literature.13,30 1H NMR (400 MHz, CDCl3): δ 3.12 (4H, m, 2 × N−CH2), 3.86 (4H, m, 2 × O− CH2), 6.81−6.86 (2H, m, HAr), 7.20−7.26 (2H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 49.3 (N−CH2), 66.7 (O−CH2), 116.9 (CHAr), 124.8 (Cl−CIVAr), 129.0 (CHAr), 149.9 (N−CIVAr). 4-Chloro-N-(2,6-dimethylphenyl)-2-methylaniline (Table 6, Entry 5). The general procedure yielded the pure arylamine as a white solid. 1H NMR (400 MHz, CDCl3): δ 2.22 (6H, s, 2 × CH3), (3H, s, CH3), 4.94 (1H, bs, NH), 6.10 (1H, d, J = 8.7 Hz, HAr), 6.95 (1H, bdd, J = 8.7, 2.6 Hz, HAr), 7.11−7.20 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 17.4 (CH3), 18.1 (CH3), 112.7 (CHAr), 122.5 (Cl−CIVAr), 124.0 (CIVAr), 125.9 (CHAr), 126.6 (CHAr), 128.6 (CHAr), 129.9 (CHAr), 135.5 (CIVAr), 138.2 (CIVAr), 142.8 (CIVAr). HRMS (ESI+): found m/z [M + H]+ 246.1042, calcd for C15H17NCl 246.1044. 4-(2-Chlorophenyl)morpholine (Table 6, Entry 6). The general procedure yielded the pure arylamine as a colorless oil. Data were in full agreement with those reported in the literature.31 1H NMR (400 MHz, CDCl3): δ 3.06 (4H, m, 2 × N−CH2), 3.88 (4H, m, 2 × O− CH2), 7.00 (1H, dt, J = 7.9, 1.5 Hz, HAr), 7.04 (1H, dd, J = 8.0, 1.5 Hz,

HAr), 7.24 (1H, ddd, J = 7.9, 1.5, 0.9 Hz, HAr), 7.37 (1H, dd, J = 7.9, 1.5 Hz, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 51.6 (N−CH2), 67.0 (O−CH2), 120.2 (CHAr), 123.8 (CHAr), 127.6 (CHAr), 128.7 (Cl−CIVAr), 130.6 (CHAr), 148.9 (N−CIVAr). 2-Chloro-N-methyl-N-phenylaniline (Table 6, Entry 7). The general procedure yielded the pure arylamine as a yellowish oil. Data were in full agreement with those reported in the literature.32 1H NMR (400 MHz, CDCl3): δ 3.32 (3H, s, CH3), 6.68 (2H, bd, J = 7.9 Hz, HAr), 6.84 (1H, bt, J = 7.3 Hz, HAr), 7.27 (3H, m, HAr), 7.35 (2H, m, HAr), 7.56 (1H, bd, J = 7.9 Hz, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 38.9 (CH3), 113.5 (CHAr), 117.8 (CHAr), 127.3 (CHAr), 128.1 (CHAr), 128.9 (CHAr), 130.1 (CHAr), 130.9 (CHAr), 133.5 (Cl− CIVAr), 145.3 (N−CIVAr), 148.5 (N−CIVAr). HRMS (ESI+): found m/z [M + H]+ 218.0731, calcd for C13H13NCl 218.0731.

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ASSOCIATED CONTENT

S Supporting Information *

Figures giving 1H and 13C NMR spectra for all compounds and a CIF file giving crystallographic data for 1. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge the EC for funding through the seventh framework programme SYNFLOW. We thank the EPSRC National Mass Spectrometry Service Center in Swansea for mass spectroscopic analyses. Johnson Matthey (Dr. Chris Barnard) and Umicore (Dr. Ralf Karch) are thanked for their generous gifts of materials. S.P.N. is a Royal Society Wolfson Research Merit Award holder.

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REFERENCES

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