Direct Arylation Mediated by Palladium Complexes with Rigid

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Organometallics 2009, 28, 2837–2847

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Direct Arylation Mediated by Palladium Complexes with Rigid Phosphine-Functionalized N-Heterocyclic Carbenes Chien-Chang Ho,† Sandipan Chatterjee,† Tzu-Liang Wu,† Kai-Ting Chan,† Yu-Wei Chang, Tsun-Hung Hsiao, and Hon Man Lee* Department of Chemistry, National Changhua UniVersity of Education, Changhua 50058, Taiwan, Republic of China ReceiVed February 12, 2009

New phosphine-functionalized N-heterocyclic carbene ligand precursors (L1H · I and L2H · I) were prepared. The former compound contains a PPh2 moiety, whereas the latter one has a more electrondonating PCy2 group. A reaction of L1H · · · I with PdCl2 in the presence of base afforded the complex PdL1ClI. An interconversion process between the two structural isomers of PdL1ClI was observed by variable-temperature NMR. The coalescence temperature (Tc) is at 368 K with the free energy of activation (∆Gq) found to be 68.9 kJ mol-1. A similar reaction of L2H · I with PdCl2 produced a mixture of PdL2ClI, PdL2Cl2, and PdL2I2. Unlike PdL1ClI, PdL2ClI undergoes a much faster exchange between the two structural isomers. Pure PdLI2 (L ) L1 and L2) can be obtained by adding NaI in the reaction mixture to facilitate ligand exchange. [PdL(CH3CtN)2](BF4)2 were also prepared straightforwardly by salt metathesis reactions. In total, seven new palladium complexes of L were structurally characterized, and in each of these structures an anagostic interaction exists between the palladium center and one of the diastereotopic methylene protons. The interaction also exists in solution, as evidenced by the downfield NMR shift of the proton. The new complexes PdLI2 and [PdL(CH3CtN)2](BF4)2 show mediocre activities in benchmark Suzuki coupling reactions under conventional and microwave heating. They are, however, highly promising in mediating direct arylation of phenyl halides and diphenylacetylene, affording 9-benzylidene-9H-fluorene in good yields. Introduction N-Heterocyclic carbenes (NHCs) and their complexes are attracting much interest due to their activities in diverse catalytic reactions.1-8 There is also interest in the preparations of functionalized NHC ligands,9-11 i.e., the incorporation of different functional groups on NHC backbones. The higher stability of chelate NHC complexes, a wide choice of donor atoms for fine-tuning ligand properties, and the formation of hemilabile ligands by virtue of the strong coordination of NHC over other donor atoms are among some of the desirable factors for such functionalized ligands. Along these directions, we have focused on phosphine-functionalized NHCs12-14 because the * Corresponding author. Tel: +886 4 7232105, ext. 3523. Fax: +886 4 7211190. E-mail: [email protected]. † The four authors contributed equally to the work. (1) Perry, M. C.; Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951. (2) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed. 2007, 46, 2768. (3) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366. (4) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.; Nolan, S. P. J. Organomet. Chem. 2002, 653, 69. (5) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18. (6) Dı´ez-Gonza´lez, S.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 349. (7) Kamber, N. E.; Jeong, W.; Waymouth, R. M.; Pratt, R. C.; Lohmeijer, B. G. G.; Hedrick, J. L. Chem. ReV. 2007, 107, 5813. (8) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290. (9) Herrmann, W. A.; Ko¨cher, C.; Goossen, L. J.; Artus, G. R. J. Chem.sEur. J. 1996, 2, 1627. (10) Ku¨hl, O. Chem. Soc. ReV. 2007, 36, 592. (11) Lee, H. M.; Lee, C.-C.; Cheng, P.-Y. Curr. Org. Chem. 2007, 11, 1491. (12) Lee, H. M.; Zeng, J. Y.; Hu, C. H.; Lee, M. T. Inorg. Chem. 2004, 43, 6822. (13) Lee, C.-C.; Ke, W.-C.; Chan, K.-T.; Lai, C.-L.; Hu, C.-H.; Lee, H. M. Chem.sEur. J. 2007, 13, 582.

phosphine ligand is another class of ligand that has been utilized efficiently for decades in homogeneous catalysis.15 Hence, the combination of NHC and phosphine can offer a new class of hybrid ligands, which is capable of possessing interesting catalytic properties.16-29 We are interested in the ligand systems L1 and L2 shown in Chart 1. Compared with other reported phosphine-functionalized NHC systems,9,13,14,16-18 the ligands from this work are more rigid in nature. Thus a higher thermal stability of their metal (14) Lee, H. M.; Chiu, P. L.; Zeng, J. Y. Inorg. Chim. Acta 2004, 357, 4313. (15) Pignolet, L. H. Homogeneous Catalysis with Metal Phosphine Complexes; Plenum Press: New York, 1983. (16) Danopoulos, A. A.; Tsoureas, N.; Macgregor, S. A.; Smith, C. Organometallics 2007, 26, 253. (17) Stylianides, N.; Danopoulos, A. A.; Tsoureas, N. J. Organomet. Chem. 2005, 690, 5948. (18) Yang, C.; Lee, H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511. (19) Wang, A.-E.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. Tetrahedron 2005, 61, 259. (20) Zhong, J.; Xie, J.-H.; Wang, A.-E.; Zhang, W.; Zhou, Q.-L. Synlett 2006, 8, 1193. (21) Field, L. D.; Messerle, B. A.; Vuong, K. Q.; Turner, P. Organometallics 2005, 24, 4241. (22) Nanchen, S.; Pfaltz, A. HelV. Chim. Acta 2006, 89, 1559. (23) Tsoureas, N.; Danopoulos, A. A.; Tulloch, A. A. D.; Light, M. E. Organometallics 2003, 22, 4750. (24) Gischig, S.; Togni, A. Organometallics 2004, 23, 2479. (25) Gischig, S.; Togni, A. Eur. J. Inorg. Chem. 2005, 2005, 4745. (26) Hahn, F. E.; Jahnke, M. C.; Pape, T. Organometallics 2006, 25, 5927. (27) Wang, A.-E.; Zhong, J.; Xie, J.-H.; Li, K.; Zhou, Q.-L. AdV. Synth. Catal. 2004, 346, 595. (28) Seo, H.; Park, H.; Kim, B. Y.; Lee, J. H.; Son, S. U.; Chung, Y. K. Organometallics 2003, 22, 618. (29) Becht, J.-M.; Bappert, E.; Helmchen, G. AdV. Synth. Catal. 2005, 347, 1495.

10.1021/om900112y CCC: $40.75  2009 American Chemical Society Publication on Web 04/17/2009

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Ho et al.

coordination chemistry are presented. While these new complexes are only mediocre in catalyzing benchmark Suzuki crosscoupling reactions, we are delighted that they are highly effective in the intermolecular direct arylation between an aryl halide and an alkyne. In particular, in contrast to the existing catalytic systems,33,34 the new palladium precatalysts are capable of utilizing less reactive phenyl bromide as a coupling partner for the formation of 9-benzylidene-9H-fluorene.

Results and Discussion

Figure 1. Variable-temperature 31P{1H} NMR spectra of PdL1ClI (4) dissolved in DMF-d7. Chart 1. Phosphine-Functionalized N-Heterocyclic Carbene Ligands

complexes was anticipated. Zhou et al. has published a ligand similar to L1, which in combination with palladium precursors shows coupling activities with a variety of aryl halides in the Heck reaction19 and Suzuki coupling.27 Helmchen et al. also reported a chiral NHC ligand relevant to L1 and its rhodium complex afforded high yields and enantioselectivities in conjugate additions of arylboronic acids to enones and R,βunsaturated esters.29 So far, all the reported phosphine-NHC hybrid ligands were functionalized with PPh2 moieties;16-29 rather surprisingly, none of them are based on the more electrondonating PR2 group (R ) alkyl). Although palladium NHC complexes have proven remarkably useful in Suzuki-type coupling reactions,2-4 alternative methods to construct the biaryl motif with reduced waste and in fewer steps are much more desirable. Thus the more challenging direct arylation without the need of an organometallic reagent is an attractive alternative.30 The coupling reaction involves a kinetically significant aryl C-H bond activation step, and aryl iodides were predominately employed as coupling partners.30 Palladium NHC complexes have been shown to be highly promising in mediating the coupling reaction.31,32 For example, Fagnou et al. reported that electron-rich palladium NHC complexes were effective in intramolecular direct arylations for the formation of six- and five-membered ring biaryls with aryl chlorides.31 Herein we introduce a PCy2 group to a NHC ligand backbone, obtaining the more electron-donating ligand L2. The syntheses of several new palladium complexes with L1 and L2 and their (30) Alberico, D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107, 174. (31) Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 1857. (32) Toure, B. B.; Lane, B. S.; Sames, D. Org. Lett. 2006, 8, 1979.

Preparation of Ligand Precursors. The preparation of new ligand precursors L1H · I (2) and L2H · I (3) is shown in Scheme 1. A common intermediate for 2 and 3 is the imidazolium salt 1, which can be obtained in quantitative yield by treating 1-(2fluorobenzyl)-1H-imidazole with excess MeI. A reaction between 1 and HPPh2 in the presence of KOBut at room temperature afforded pure 2 in 40% yield. A ligand precursor relevant to 2 was published by Zhou et al.19 Compound 3 can be prepared similarly. The reaction, however, had to be conducted at -78 °C with a stronger base of BunLi. A decent yield of 71% was obtained. The methylene protons for 2 and 3 resonate at 5.69 and 5.82 ppm, respectively. Their 31P{1H} NMR signals are at -17.6 and -15.5 ppm, respectively. Both compounds are hygroscopic and sensitive toward air. Preparation of Chelate Palladium Complexes. The preparation of chelate palladium complexes with L followed a protocol of reacting a ligand precursor and PdCl2 in the presence of NaOAc in DMF (Schemes 2 and 3). The reaction between 2 and PdCl2, consisting of two kinds of halides, afforded the mixed-halo complexes PdL1ClI in low yields. The 31P{1H} NMR spectrum in DMF-d7 displays two broad signals at 7.0 and 11.6 ppm with an integration ratio of ca. 1:1. The presence of two signals can be attributed to the formation of two structural isomers (4A and 4B). The structural isomer 4A was revealed by the crystallographic analysis on a crystal obtained from the mixture (vide infra). The 31P{1H} NMR spectrum of the batch of crystals used for crystallographic work indicated that the upfield signal at 7 ppm is due to 4A. Interestingly, the two isomers are in dynamic exchange, as revealed by a variabletemperature NMR experiment (vide infra). Intriguingly, a similar reaction between the imidazolium salt 3 and PdCl2 produced apparently a mixture of three species according to 31P{1H} NMR spectroscopy. Instead of two broad signals due to mixed-halide complexes, three sharp signals are observed at 17.4, 21.3, and 26.1 ppm, respectively, in a ratio of 64:18:18. Unfortunately, these three species could not be separated from each other. To reveal their identities, crystals were obtained from the mixture. Subsequent structural studies on two kinds of crystals revealed the formation of a mixedhalide complex, PdL2ClI (6), and a dichloro complex, PdL2Cl2 (7). Their 31P NMR resonances are at 17.4 and 26.1 ppm, respectively, as revealed by their spectra from the crystal samples. The signal at ca. 21 ppm attributable to a diiodo complex, PdL2I2 (8), was confirmed by an authentic synthesis of the compound (vide infra). Contrastingly, no PdL1I2 and PdL1Cl2 were isolated from the corresponding reaction between 2 and PdCl2. The difference can be attributed to the better solubility of the complexes with L1 than those of L2, such that they were lost during the workup procedure. Pure diiodo palladium complexes PdL1I2 (5) and PdL2I2 (8) can be obtained by adding excess NaI in the reaction mixture (33) Tian, Q.; Larock, R. C. Org. Lett. 2000, 2, 3329. (34) Larock, R. C.; Tian, Q. J. Org. Chem. 2001, 66, 7372.

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Scheme 1. Synthesis of Ligand Precursors

Scheme 2. Synthesis of Palladium NHC Complexes Bearing L1

Scheme 3. Synthesis of Palladium NHC Complexes Bearing L2

to facilitate halide exchange. Both compounds are brownish solids with high melting points (5: 252 °C; 8: 330 °C). The solubility of 5 in halogenated solvents is higher than that of 8. The formation of a single product was indicated by a single 31P NMR signal in each of their spectra. In both 5 and 8, due to the complexation, the two methylene protons become diastereotopic. Markedly, in both compounds, the chemical shift differences between these two diastereotopic protons are quite large. In the spectrum of 5, one doublet resonates at 5.00 ppm, whereas the other one is at a very downfield position of ca. 6.91 ppm, overlapping with one aryl proton. Thus, a chemical shift difference of ca. 1.9 ppm is observed. Indeed, the latter signal was shifted ca. 1.2 ppm downfield compared with the CH2 proton on the ligand precursor 2. Similarly in 8, the two methylene doublets are observed at 4.66 and 6.43 ppm, with a chemical shift difference of ca. 1.8 ppm.35 In fact, the large downfield shift of these protons can be related to the presence of an anagostic interaction in the structure (vide infra). In the 13C{1H} NMR spectrum of 5, the carbene signal is observed as a doublet at 142.3 ppm (2J(PC) ) 11.6 Hz), whereas in the spectrum of 8, two downfield quaternary (35) See the 1H NMR spectrum of 8 in the Supporting Information.

carbon singlets at 143.00 and 157.60 ppm were observed. To distinguish unambiguously which signal belongs to the carbene carbon, a HMBC (heteronuclear multiple-bond correlation) experiment was performed. The presence of correlation peaks from the more downfield resonance toward the CH3 proton signal confirmed that the 157.60 ppm singlet is due to the carbene carbon. The carbene signal, being a doublet in 5 but a singlet in 8, may be related to the rapid fluxional process in 8 (vide infra). The difference in electronic property between 5 and 8 is also reflected in the δ values of the carbene and the 31P NMR resonances. The carbene signal for 8 is ca. 15.3 ppm more downfield than that of 5. The 31P NMR signal for 5 is at 8.6 ppm, whereas that for 8 resonates at a more downfield position of 21.7 ppm. Ionic complexes with acetonitrile ligands [PdL1(MeCtN)2](BF4)2 (9) and [PdL2(MeCtN)2](BF4)2 (10) were produced by salt metathesis between the diiodo complexes 5 and 8 with AgBF4 in acetonitrile solvent (Scheme 4). These complexes are highly hygroscopic and of very poor solubility in halogenated solvents. The presence of acetonitrile ligands was unambiguously confirmed by the CtN stretching bands in their IR spectra. For example in 10, the two bands are at 2300 and 2372 cm-1,

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Figure 2. Molecular structure of 4A with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction. Hydrogen atoms except those on C5 have been omitted for clarity. Only one of the two independent molecules in the asymmetric unit is shown. Scheme 4. Synthesis of Ionic Palladium NHC Complexes

Ho et al.

Figure 3. Molecular structure of 6 with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction and the disordered halides. Hydrogen atoms except those on C5 have been omitted for clarity. Atom labels with “A” are associated with the minor orientation. Scheme 5. Fluxional Isomerization in 4 at Elevated Temperature

which compared favorably with those reported in the literature.36,37 The weakly coordinating acetonitrile ligands can be easily displaced by other nucleophiles; thus crystallization of 9 and 10 in pyridine/diethyl ether yielded [PdL1(py)2](BF4)2 (11) and [PdL2(py)2](BF4)2 (12), respectively. Variable-Temperature NMR Spectroscopy. We were interested in understanding whether the two structural isomers of 4 will undergo dynamic exchange or not, with regard to the close spacing of the two resonances in the 31P{1H} NMR spectrum. Variable-temperature 31P{1H} NMR spectra of a DMF-d7 solution of 4 were obtained, revealing the coalescence of signals at 95 °C (Figure 1 and Scheme 5). The rate constant, kc, of the dynamic exchange at the coalescence was calculated from the equation kc ) πµ∆ν/2, where ∆ν ) the difference in resonance frequencies determined in the slow exchange limit. Using ∆ν ) 569 Hz, kc was found to be 1264 s-1. Then applying q the Eyring equation38,39 (kc ) (kBTc/h)e(-∆G /RTc)), the free energy (36) Gardiner, M. G.; Herrmann, W. A.; Reisinger, C.-P.; Schwarz, J. g.; Spiegler, M. J. Organomet. Chem. 1999, 572, 239. (37) Bernatis, P. R.; Miedaner, A.; Haltiwanger, R. C.; DuBois, D. L. Organometallics 1994, 13, 4835. (38) Eyring, H. Chem. ReV. 1935, 17, 65. (39) Jeannin, O.; Delaunay, J.; Barriere, F.; Fourmigue, M. Inorg. Chem. 2005, 44, 9763.

of activation (∆Gq) was calculated to be 68.9 kJ mol-1 (16.5 kcal mol-1). In contrast, the exhibition of one sharp 31P NMR signal due to 6 at room temperature suggested a much faster exchange process. In fact, the signal at 17 ppm remained sharp on cooling a CD2Cl2 solution containing 6 at the lowest attainable temperature permitted by the solvent. Crystallographic Studies. Figure 2-8 display thermal ellipsoid plots of 4A, 6, 5, 8, 7, 11, and 12, respectively. The crystallographic details are given in Table 1. Selected bond distances and angles are summarized in Table 2. Complex 4a crystallizes in the monoclinic unit cell with space group P21/n having two independent molecules in an asymmetric unit. The geometric parameters of these two molecules are similar, and hence one of them was chosen for the structural discussion. All other complexes crystallize with one independent molecule in their respective asymmetric units. The sites of Cl and I atoms in 6 are disordered among each other (vide infra). The solvent inclusion in the crystal lattice of 7 is of considerable disorder

Figure 4. Molecular structure of 5 with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction. Hydrogen atoms except those on C5 have been omitted for clarity.

Direct Arylation Mediated by Palladium Complexes

Figure 5. Molecular structure of 8 with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction. The CHCl3 solvent molecule and hydrogen atoms except those on C5 have been omitted for clarity.

Figure 6. Molecular structure of 7 with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction. Hydrogen atoms except those on C5 have been omitted for clarity.

Figure 7. Cationic portion of 11 with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction. Hydrogen atoms except those on C5 have been omitted for clarity.

and thus not indentified and refined. The disorder guest chloroform molecule in 8 and one of the disordered tetrafluoroborate anions in 12 were modeled successfully. In general, the Pd1 in each structure is in a distorted square coordination geometry. The distortion can be inferred by the nonlinearity of the two bond angles about the metal center. For

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Figure 8. Cationic portion of 12 with 50% probability ellipsoids for non-H atoms, showing the C-H · · · Pd interaction. Hydrogen atoms except those on C3 have been omitted for clarity.

example in 5, the ∠C1-Pd1-I1 ) 176.10(9)° and ∠P1-Pd1-I2 ) 172.19(2)° derivate significantly from the ideal 180°. The bulky L2 has a bigger bite angle than L1, reflecting the larger ∠C-Pd-P of 89.54(11)° in 6, 93.82(18)° in 7, 90.4(2)° in 8, and 88.41(5)° in 12 than that of 83.1(4)° in 4A, 84.62(8)° in 5, and 82.73(11)° in 11. Interestingly, vapor diffusion of diethyl ether into a DMF solution of 4 allowed the isolation of crystals for isomer 4A as revealed by the diffraction study and the 31P{1H} NMR spectroscopy. Indeed, 4A is a mixed-halo complex; the I atom is trans to the P atom, whereas the Cl atom is trans to the carbene moiety. The isomer 4B is absent in the crystal lattice. In sharp contrast, the refinement of the structure obtained from 6 revealed the presence of both structural isomers in the crystal lattice (Figure 3). The Cl and I atoms are disordered among each other. The major isomer 6A is similar to 4A, having the I atom trans to the P atom. The amount of the major isomer 6A is about 83%, reflecting the occupancy factor. In fact, the structural model of 6 is in accord with the NMR data of the two structural isomers in fast exchange (vide supra). As indicated in both 5 and 8, the Pd-I bonds trans to the P atoms are longer than those trans to the carbene moieties, implying a bigger trans influence exerted by phosphine than carbene. For example in 8, the Pd-I distance trans to P is 2.6613(7) Å, whereas that trans to carbene is 2.6031(9) Å. It is even obvious in 7; the Pd-Cl distance trans to P is longer than that trans to carbene by as much as 0.13 Å. Consistently, the Pd-N distances trans to the P atoms are also longer than those trans to the carbene in 11 and 12. The Pd-carbene bond distances of 1.941(12)-1.998(3) Å in these seven new complexes are in the usual range of reported palladium NHC complexes.40-44 The larger steric bulkiness of L2 can be clearly seen in Figure 9. The pyridine trans to the carbene moiety is tilted significantly away from the steric bulk of the PCy2 group in 12. In fact, the interangle between the Pd-C axis and the N-C axis of the (40) Lebel, H.; Janes, M. K.; Charette, A. B.; Nolan, S. P. J. Am. Chem. Soc. 2004, 126, 5046. (41) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101. (42) Catalano, V. J.; Etogo, A. O. Inorg. Chem. 2007, 46, 5608. (43) Chiu, P. L.; Lai, C. L.; Chang, C. F.; Hu, C. H.; Lee, H. M. Organometallics 2005, 24, 6169. (44) Lee, H. M.; Lu, C. Y.; Chen, C. Y.; Chen, W. L.; Lin, H. C.; Chiu, P. L.; Cheng, P. Y. Tetrahedron 2004, 60, 5807.

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Ho et al. Table 1. Crystallographic Data

empirical formula fw cryst syst space group a, Å b, Å c, Å R, deg β, deg γ, deg V, Å3 T, K Z no. of unique data no. of params refined R1a [I > 2σI] wR2b (all data) peak/hole (e Å-3) a

4A

5

6

7

8

11

12

C23H21ClIN2PPd 625.14 monoclinic P21/n 16.560(5) 15.826(4) 18.149(5) 90 106.401(6) 90 4563(2) 150(2) 8 10 493 513 0.0730 0.1943 1.056/-2.189

C23H21I2N2PPd 716.59 monoclinic P21/c 10.7155(6) 13.1275(7) 16.9624(9) 90 97.8700(10) 90 2363.6(2) 150(2) 4 6142 263 0.0288 0.0754 1.313/-1.277

C23H33ClIN2PPd 673.23 monoclinic P21/c 15.8611(7) 14.6215(7) 11.4331(5) 90 111.13 90 2473.28(19) 150(2) 4 6314 270 0.0359 0.0952 1.022/ -1.373

C23H33Cl2N2PPd 545.78 rhombohedral R3j 35.9388(9) 35.9388(9) 10.4874(5) 90 90 120 11730.7(7) 150(2) 18 6824 263 0.0665 0.2297 2.349/-1.107

C24H33I2N2PPd · CHCl3 542.99 triclinic P1j 10.3898(2) 12.2079(2) 12.3724(2) 101.3740(10) 100.1470(10) 96.7930(10) 1495.24(4) 150(2) 2 7636 309 0.0602 0.1839 2.296/-4.913

C33H31B2F8N4PPd 794.61 orthorhombic Pna21 19.9738(6) 11.0019(3) 15.4627(5) 90 90 90 3397.92(18) 150(2) 4 8561 443 0.0476 0.1174 0.933/-0.646

C33H43B2F8N4PPd 806.70 monoclinic P21/n 10.2988(6) 22.6880(13) 15.4923(9) 90 98.8950(10) 90 3576.4(4) 150(2) 4 9489 470 0.0297 0.0778 1.770/-0.390

R1 ) ∑(|Fo| - |Fc|)/∑|Fo|. b wR2 ) [∑(|Fo|2 - |Fc|2)2/∑(Fo2)]1/2.

pyridine ring is about 14° in 12, whereas the two axes in 11 are almost parallel. A feature worthy of mentioning is the presence of an anagostic interaction45 in all the structures between one of the methylene protons and the Pd center. Anagostic interactions are C-H · · · M electrostatic interactions typically occurring in d8 transition metal centers that are square planar.46,47 The interactions are characterized by M · · · H distances of 2.3-2.9 Å and M · · · H-C contact angles of 110-170°.45 All the thermal ellipsoid plots clearly depict that the ligand structure holds the methylene proton over the Pd center,48 favoring the formation of such close contact. The interacting distances and contact angles are within the range of anagostic interactions in general (see Table 2). These interactions are sustained in solution, as illustrated by the downfield chemical shifts of the anagostic protons in their NMR spectra.49 Catalytic Organic Transformations. Initially, the catalytic performances of the new complexes in benchmark Suzuki coupling reactions were evaluated. We were anticipating higher activities from complexes with the more electron-donating PCy2 group than those with the PPh2 moiety. Table 3 shows the coupling activities mediated by 5, 8, 9, and 10 under conventional heating. In general, good yields of products can be achieved with aryl bromides in about 2 h. Comparing the activities of 5 and 8, entries 1-3 vs 4-6 clearly indicated that 8, with the better donor L2, afforded a higher yield of coupled products. The ionic complex 9 delivered better yields than the neutral complex 5 (entries 7-9 vs 1-3), whereas the neutral complex 8 and the ionic complex 10 have similar activities (entries 4-6 vs 10-12). Microwave-assisted synthesis is a valuable technique for organic chemists because the radiation can enhance the reaction rate and in many cases improve product yields as well.50,51 The use of Pd(NHC) complexes in catalysis under microwave irradiation is relatively rare compared with conventional heat(45) Brookhart, M.; Green, M. L. H.; Parkin, G. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 6908. (46) Huynh, H. V.; Wong, L. R.; Ng, P. S. Organometallics 2008, 27, 2231. (47) Ruiz, J.; Lorenzo, J.; Vicente, C.; Lop´ez, G.; Loı´pez-de-Luzuriaga, J. M. a.; Monge, M.; Aviles´, F. X.; Bautista, D.; Moreno, V.; Laguna, A. Inorg. Chem. 2008, 47, 6990. (48) See also a perspective view of 5 in the Supporting Information. (49) Zhang, Y.; Lewis, J. C.; Bergman, R. G.; Ellman, J. A.; Oldfield, E. Organometallics 2006, 25, 3515. (50) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250. (51) Leadbeater, N. E. Chem. Commun. 2005, 2881.

ing.52 Hence, we also briefly explored the use of microwave radiation for the catalytic reactions mediated by the thermally more robust complexes 5 and 8. Both complexes can deliver high turnover frequencies (TOFs) when the reactions were conducted in DMF/water solvent at 150 °C under microwave irradiation for a period of 15 min. Complex 8 gave the highest TOF in the reaction with the activated substrate of 4-bromoacetophenone (entry 4). For electron-neutral and electron-donating substrates, the activities were generally lower (entries 2/3 and 5/6). The activity of 8 using 4-bromotoluene as substrate was unexpectedly low compared with that mediated by 5 (entry 5 vs 2). We then applied the explored conditions in Table 3 on the synthesis of the nonsteroid anti-inflammatory drug felbinac using 8 as the precatalyst.53 Under conventional heating, an isolated yield of the drug (70%) could be obtained in 2 h from the coupling reaction of phenylboronic acid and 2-(4-bromophenyl)acetic acid (Scheme 6). Under microwave irradiation, a higher yield (82%) was achieved in 15 min. Nevertheless, the palladium complexes failed to utilize cheap aryl chlorides as substrates in the coupling reactions. Overall, these complexes with the rigid phosphine-functionalized NHC ligands delivered inferior activities to those from complexes with more flexible ligands in Suzuki-type coupling reactions. We then explored the possibility of applying the new palladium complexes in direct arylation of phenyl halides and diphenylacetylene for the formation of 9-benzylidene-9H-fluorene. The cascade reaction is typically catalyzed by a high loading of Pd(OAc)2 (5 mol %) and PPh3 (10 mol %) at high temperature over a long duration.33 Considering the harsh catalytic conditions required, the robust palladium complexes with the rigid phosphine-functionalized NHC ligands might exhibit better activities. The catalytic conditions employed were similar to those utilized by Larock et al. (Table 4).33 It was confirmed that no product could be formed in the absence of palladium complex (entries 1 and 2). Entries 3 and 4 reveal that 5 mol % of 8, 1 equiv of phenyl iodide, 1 equiv of diphenylacetylene, 2 equiv of NaOAc, and 1 equiv of n-Bu4NCl in 5 mL of DMF at 120 °C for a duration of 24 h represent an effective protocol for quantitative production of the desired product. As shown from entries 4 vs 5 and 6, complex 8 is more active than 5 and 10. It is particularly noteworthy that 8 also exhibited good coupling activities with (52) Navarro, O.; Kaur, H.; Mahjoor, P.; Nolan, S. P. J. Org. Chem. 2004, 69, 3173. (53) Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373.

Organometallics, Vol. 28, No. 9, 2009 2843

2.837, 110.7° 2.841 Å, 109.8°

12

Pd1sC4, 1.9688(18) PdsP1, 2.2891(5) Pd1sN3, 2.1290(16) Pd1sN4, 2.1030(17) C4sPd1sP1, 88.41(5) C4sPd1sN3, 86.70(7) N3sPd1sN4, 88.70(6) P1sPd1sN4, 96.36(5) C4sPd1sN4, 174.89(7) P1sPd1sN3, 173.36(4)

11

Pd1sC1, 1.987(4) PdsP1, 2.2687(12) Pd1sN3, 2.093(3) Pd1sN4, 2.099(3) C1sPd1sP1, 82.73(11) C1sPd1sN4, 91.54(14) N3sPd1sN4, 88.62(13) P1sPd1sN3, 97.13(9) C1sPd1sN3, 178.2(3) P1sPd1sN4, 174.23(10)

Direct Arylation Mediated by Palladium Complexes

Figure 9. Comparative drawings of the cationic portions of 11 (left) and 12 (right), indicating the tilting of the pyridine ligand in 12 due to steric hindrance. Table 3. Suzuki Coupling

2.791 Å, 111.2° 2.836 Å, 110.4°

8

Pd1sC1, 1.964(8) Pd1sP1, 2.2999(19) Pd1sI1, 2.6031(9) Pd1sI2, 2.6613(7) C1sPd1sP1, 90.4(2) C1sPd1sI2, 86.6(2) I1sPd1sI2, 88.85(3) P1sPd1sI1, 94.07(5) C1sPd1sI1, 175.1(2) P1sPd1sI2, 175.55(5) Pd1sC1, 1.995(7) PdsP1, 2.2728(17) Pd1sCl1, 2.3416(18) Pd1sCl2, 2.4729(14) C1sPd1sP1, 93.82(18) C1sPd1sCl2, 90.26(17) Cl1sPd1sCl2, 87.87(6) P1sPd1sCl1, 88.17(7) C1sPd1sCl1, 174.7(2) P1sPd1sCl2, 175.75(6)

7 6

Pd1sC1, 1.993(4) Pd1sP1, 2.2909(10) Pd1sI1, 2.6631(9) Pd1sCl1, 2.458(4) C1sPd1sP1, 89.54(11) C1sPd1sI1, 87.78(11) Cl1sPd1sI1, 90.46(10) Cl1sPd1sP1, 92.34(11) C1sPd1sCl1, 176.31(13) P1sPd1sI1, 176.47(4) angles) 2.861 Å, 110.1° Pd1sC1, 1.998(3) Pd1sP1, 2.2773(8) Pd1sI1, 2.6367(3) Pd1sI2, 2.6594(3) C1sPd1sP1, 84.62(8) C1sPd1sI2, 87.73(8) I1sPd1sI2, 91.595(10) P1sPd1sI1, 95.93(2) C1sPd1sI1, 176.10(9) P1sPd1sI2, 172.19(2) distances, M · · · H-C contact 2.828 Å, 110.8°

5 4A

Pd1sC1, 1.941(12) Pd1sP1, 2.274(3) Pd1sCl1, 2.358(3) Pd1sI1, 2.6203(15) C1sPd1sP1, 83.1(4) C1sPd1sI1, 86.3(4) Cl1sPd1sI1, 92.08(9) Cl1sPd1sP1, 98.25(11) C1sPd1sCl1, 176.7(4) P1sPd1sI1, 168.45(9) Anagostic interaction (M · · · H 2.786 Å, 106.9°

Table 2. Selected Bond (Contact) Distances (Å) and Angles (deg)

entry 1 2 3 4 5 6 7 8 9 10 11 12

cat. 5

8

9

10

R

yield (%)a

TOF (h-1)

yield (%)b

TOF (h-1)

COMe Me OMe COMe Me OMe COMe Me OMe COMe Me OMe

84 81 48 100 100 88 99 (97)c 88 90 100 98 (99)c 91

14.0 13.5 8.0 16.7 16.7 14.7 16.5 (16.2) 14.7 15 16.7 16.3 (16.5) 15.2

89 67 66 100 47 70

118.7 89.3 88.0 133.3 62.7 93.3

a Conventional heating condition: 1 mmol of aryl halides, 1.5 mmol of PhB(OH)2, 2.0 mmol of Cs2CO3 as base, 3 mol % of catalyst, 3 mL of 1,4-dioxane, 2 h, 80 °C, GC yield, an average of two runs. b Microwave irradiation conditions: similar to conventional heating, except for 2.5 mL DMF/0.5 mL H2O as solvent, 15 min, 150 W, 150 °C, GC yield, an average of two runs. c Isolated yield.

Scheme 6. Preparation of the Non-steroid Anti-inflammatory Drug Felbinac

the less reactive phenyl bromide as substrate, affording a 74% yield of the pure product in 48 h (entry 8). The result is in sharp contrast to those of the reported Pd(OAc)2/PPh3 system, in which aryl iodides were solely applied.33,34 The ionic complex 10 delivered a slightly lower yield than that of the neutral complex 8 (entry 8 vs 10). Entry 8 vs 9 illustrated that 8, with the better donor L2, is much more effective in utilizing the less reactive phenyl bromide. The mechanism involved should be similar to that proposed by Larock et al.,33 and the higher activities of the new complexes may be attributed to the better supported active Pd(0) species bearing the phosphine-functionalized NHC ligands.

Conclusions We successfully prepared two new phosphine-functionalized NHC precursors for L1 and L2. In particular, L2 is the first example of a hybrid NHC ligand containing a more electrondonating PCy2 moiety. A series of their palladium complexes were synthesized. The presence of the ligand-supported anagostic interaction between the Pd center and one of the methylene protons renders the coordination of the ligands in

2844 Organometallics, Vol. 28, No. 9, 2009

Ho et al.

Table 4. Direct Arylation of Phenyl Halides and Diphenylacetylenea

entry 1 2 3 4 5 6 7 8 9 10

cat.

X

time (h)

yield (%)

TOF (d-1)

8 8 5 10 8 8 5 10

I I I I I I Br Br Br Br

24 48 24 48 48 48 24 48 48 48

0 0 >99 >99 85 77 45 74 15 51

0 0 19.8 19.8 8.5 7.7 9 7.4 1.5 5.1

a Reaction conditions: 5 mol % of catalyst, 1 mmol of phenyl halides, 1 mmol of diphenylacetylene, 2 mmol of NaOAc, 1 mmol of n-Bu4NCl, 5 mL of DMF, 120 °C, isolated yield.

these complexes highly rigid. Nevertheless, the two halide ligands in PdL1ClI undergo isomeric exchanges at elevated temperature, whereas those in PdL2ClI, with the more electrondonating, bulky L2, exchange much more rapidly. The more labilized nature of the halides in PdL2 complexes correlates well with their higher catalytic activities. Instead of Suzuki coupling reactions, the robust complexes PdL2ClI and [PdL2(CH3CtN)2](BF4)2 excel in catalyzing the more challenging direct arylation of phenyl halides and diphenylacetylene. For the first time, phenyl bromide can be used as substrate to generate 9-benzylidene-9H-fluorene. The scope of related palladium NHC complexes in catalyzing various direct arylations is being investigated.

Experimental Section General Procedure. All reactions were performed under a dry nitrogen atmosphere using standard Schlenk techniques. All solvents used were purified according to standard procedures.54 Commercially available chemicals were purchased from Aldrich or Acros. 1H, 13C{1H}, and 31P{1H} NMR spectra were recorded at 300.13, 75.48, and 121.49 MHz, respectively, on a Bruker AV300 spectrometer. The chemical shifts for 1H and 13C spectra were referenced by the residual solvent signals relative to tetramethylsilane at 0 ppm. The chemical shifts for 31P spectra were referenced to an external reference of 85% phosphoric acid at 0 ppm. Due to the limited solubility of 8, its 13C{1H} NMR spectrum was collected at 150.87 MHz on a Varian Unity Inova-600 spectrometer at the Instrument Center of National Chung Hsing University, Taiwan. Elemental analyses and ESI-MS spectra were performed on a Heraeus CHN-OS Rapid elemental analyzer and a Finnigan/Thermo Quest MAT 95XL mass spectrometer, respectively, at the Instrument Center of NCHU. Felbinac55 and 9-benzylidene-9H-fluorene33 have been previously reported. Synthesis of 1-(2-Fluorobenzyl)-1H-imidazole. A mixture of 1H-imidazole (3.00 g, 0.0440 mol), NaOH (7.04 g, 0.176 mol) in THF (25 mL), and 2-fluorobenzyl chloride (5.24 mL, 0.0440 mol) was heated under reflux for 12 h. The solvent was then removed completely under vacuum. Dichloromethane (15 mL) and water (15 mL) were added to the residue. After extraction, the organic layer was separated, dried with anhydrous MgSO4, and dried under vacuum to afford a yellowish liquid. Yield: 6.83 g, 88%. 1H NMR (54) Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 5th ed.; Elsevier Science: Burlington, 2003. (55) Alacid, E.; Na´jera, C. Org. Lett. 2008, 10, 5011.

(CDCl3): δ 4.80 (s, 2H, CH2), 6.64 (s, 1H, imi-H), 6.72-6.81 (m, 4H, imi-H, Ar-H), 6.94-7.02 (m, 1H, Ar-H), 7.27 (s, 1H, NCHN). 13 C{1H} NMR (CDCl3): δ 44.4 (d, 3JCF ) 4.6 Hz, CH2), 115.6 (d, 2 JCF ) 21.1 Hz, Ar-C), 119.1 (s, imi-C), 123.5 (d, 2JCF ) 14.5 Hz, Ar-C), 124.6 (d, 4JCF ) 3.6 Hz, imi-C), 129.7 (Ar-C, imi-C), 130.2 (d, 3JCF ) 8.2 Hz, Ar-C), 137.3 (NCN), 160.3 (d, 1JCF ) 247.4 Hz, CF). Positive mode ESI-MS (CH2Cl2): m/z 177.3 [M + I]+. Synthesis of 1-(2-Fluorobenzyl)-3-methylimidzolium Iodide (1). A mixture of 1-(2-fluorobenzyl)-1H-imidazole (3.99 g, 22.7 mmol) and iodomethane (4.23 mL, 68.0 mmol) was dissolved in THF (25 mL). It was then heated under reflux for 12 h. The solvent was then removed completely under vacuum. Upon addition of THF (20 mL), a white solid was obtained. It was then filtered, washed with more THF (20 mL), and dried under vacuum. Yield: 7.14 g, 99.0%. Anal. Calcd for C11H12N2FI: C, 41.53; H, 3.80; N, 8.81. Found: C, 41.29; H, 3.93; N, 8.53. 1H NMR (CDCl3): δ 4.04 (s, 3H, NCH3), 5.52 (s, 2H, NCH2), 6.97 (t, 3JHH ) 9.0 Hz, 1H, ArH), 7.06 (t, 3JHH ) 7.5 Hz, 1H, Ar-H), 7.23-7.31 (m, 1H, Ar-H), 7.38 (s, 1H, imi-H), 7.60 (s, 1H, imi-H), 7.65 (t, 3JHH ) 7.5 Hz, 1H, Ar-H), 9.81 (s, 1H, NCHN). 13C{1H} NMR (CDCl3): δ 37.1 (NCH3), 47.2 (d, 3JCF ) 3.5 Hz, NCAr), 115.9 (d, 2JCF ) 20.8 Hz, Ar-C), 120.1 (d, 2JCF ) 14.5 Hz, Ar-C), 122.2 (imi-C), 124.0 (ArC), 125.2 (imi-C), 131.7 (d, 2JCF ) 2.8 Hz, Ar-C), 131.9 (d, 3JCF ) 8.4 Hz, Ar-C), 136.4 (NCN), 160.7 (d, 1JCF ) 248.4 Hz, CF). Positive mode ESI-MS (DMF): m/z 191.1 [M - I]+. Synthesis of L1H · I (2). A sample of HPPh2 (0.95 mL, 5.43 mmol) was injected via a syringe into a DMSO solution (3 mL) of KOBut (0.61 g, 5.43 mmol). The solution changed immediately into a blood-red color. It was allowed to stir at room temperature for 0.5 h. The solution was added dropwise via a syringe into a DMSO (5 mL) solution of 1 (1.82 g, 5.72 mmol). The solution was then stirred for 12 h. The solvent was removed completely under vacuum. Degassed methanol (20 mL) was added to the residue, and the resultant mixture was stirred for 2-3 h. It was allowed to pass through a plug of Celite under nitrogen. The solvent of the filtrate was completely removed under vacuum. The residue was washed with water (15 mL) and extracted with dichloromethane (15 mL). After separation, the volume of the organic solvent was reduced to about 3 mL. Upon addition of diethyl ether, a yellow solid was formed. It was filtered on a frit, washed with more diethyl ether, and dried under vacuum. Yield: 1.10 g, 40%. Anal. Calcd for C23H22N2PI · H2O: C, 54.99; H, 4.82; N, 5.58. Found: C, 54.45; H, 4.25; N, 5.48. 1H NMR (CDCl3): δ 3.76 (s, 3H, CH3), 5.69 (s, 2H, CH2), 6.94-6.97 (m, 1H, Ar-H), 7.03-7.11 (m, 6H Ar-H), 7.23 (s, 1H, imi-H), 7.24-7.35 (m, 6H, imi-H, Ar-H), 7.42-7.50 (m, 1H, Ar-H), 7.75-7.79 (s, 1H, imi-H), 9.33 (s, 1H, NCHN). 13 C{1H} NMR (CDCl3): δ 36.9 (NCH3), 52.2 (d, 3JPC ) 21.7 Hz, CH2), 121.6 (imi-C), 123.1 (imi-C), 128.8 (d, JPC ) 7.2 Hz, ArC), 129.3 (Ar-C), 130.4 (d, JPC ) 17.6 Hz, Ar-C), 131.7 (d, JPC ) 10.2 Hz, Ar-C), 131.9 (d, JPC ) 4.6 Hz, Ar-C), 133.64 (d, JPC ) 19.6 Hz, Ar-C), 134.5 (d, JPC ) 7.8 Hz, Ar-C), 134.9 (Ar-C), 136.5 (d, JPC ) 25.9 Hz, Ar-C), 136.8 (NCN), 137.1 (d, JPC ) 15.5 Hz, Ar-C). 31P{1H} NMR (CDCl3): δ -17.6. Positive mode ESI-MS (DMF): m/z 357.0 [M - I]+. Synthesis of L2H · I (3). A hexane solution of HPCy2 (7.8 mL, 3.93 mmol) was diluted in dry THF (7 mL) at -78 °C. It was then treated with a hexane solution of n-BuLi (2.4 mL, 3.85 mmol). The mixture was stirred for 1 h at -78 °C under N2 atmosphere. The solution was quickly transferred via a cannula to a solid sample of 1 (500 mg, 1.57 mmol). The resultant mixture was stirred at -78 °C for 1 h and then allowed to attain ambient temperature slowly. The stirring was continued for 48 h. The solvent was removed completely under vacuum. Degassed methanol (25 mL) was added to the residue, and the resultant mixture was stirred for 15 min. It was then filtered through a plug of Celite. The solvent was removed completely again. The residue was washed with diethyl ether (2 × 25 mL) and hexane (25 mL). The off-white solid

Direct Arylation Mediated by Palladium Complexes was dried under vacuum. Yield: 0.550 g, 71%. Anal. Calcd for C23H34N2PI: C, 55.65; H, 6.90; N, 5.64. Found: C, 54.45; H, 5.40; N, 5.23. 1H NMR (CDCl3): δ 0.81-1.93 (m, 22H, Cy-H), 4.06 (s, 3H, CH3), 5.82 (s, 2H, CH2), 7.29 (s, 1H, imi-H), 7.31 (s, 1H, imiH), 7.34-7.41 (m, 2H, Ar-H), 7.46-7.51 (m, 1H, Ar-H) 7.71-7.74 (m, 1H, Ar-H), 10.07 (s, 1H, NCHN). 13C{1H} NMR (CDCl3): δ 26.0 (Cy-C), 26.7 (d, 3JPC ) 8.2 Hz, Cy-C), 26.8 (d, 2JPC ) 13.2 Hz, Cy-C), 28.8 (d, 3JPC ) 7.1 Hz, Cy-C), 30.1 (d, 2JPC ) 16.4 Hz, Cy-C), 33.4 (d, 1JPC ) 11.3 Hz, PCH), 37.0 (CH3), 51.1 (d, 3JPC ) 26.0 Hz, CH2), 121.6 (d, 2JPC ) 5.5 Hz, Ar-C), 123.3 (imi-C), 129.1 (Ar-C), 130.1 (imi-C), 131.2 (d, 3JPC ) 4.8 Hz, Ar-C), 133.5 (d, 3 JPC ) 3.0 Hz, Ar-C), 134.9 (d, 1JPC ) 22.2 Hz, Ar-C), 136.5 (NCN), 139.2 (d, 2JPC ) 25.7 Hz, Ar-C). 31P{1H} NMR (CDCl3): δ -15.5. Positive mode ESI-MS (DMF): m/z 369.8 [M - I]+. Synthesis of PdL1ClI (4). A mixture of 2 (0.300 g, 0.619 mmol) and NaOAc (0.050 g, 0.619 mmol) was stirred in DMF (5 mL). A sample of PdCl2 (0.109 g, 0.619 mmol) was then added, and the resultant mixture was heated at 75 °C for 2 h. After cooling, the solvent was removed completely under vacuum. The residue was washed with water (15 mL) and extracted with dichloromethane (15 mL). The organic layer was dried with anhydrous MgSO4. After filtration, the solvent was removed completely under vacuum. The residual brownish solid was washed with THF (15 mL × 2), filtered on a frit, and dried under vacuum. The product is a mixture of 4A and 4B. Yield: 0.108 g, 28%. Anal. Calcd for C23H21N2PIClPd: C, 44.19; H, 3.39; N, 4.48. Found: C, 43.99; H, 3.51; N, 4.46. 31P{1H} NMR (DMF-d7): δ 7.0 (4A), 11.6 (4B). The integration ratio is ca. 1:1. ESI-MS (DMF): m/z 571.8 [M - I + DMF]+. A 61:39 mixture of 4A and 4B was obtained after recrystallization using DMF and diethyl ether. Complex 4A was characterized from this mixture. 1 H NMR (DMSO-d6): δ 3.31 (br s, 3H, NCH3), 5.34 (d, 2JHH ) 14.7 Hz, 1H, NCHAHB), 6.56-6.60 (br s, 1H, NCHAHB), 6.59-6.95 (m, 1H Ar-H), 7.23-7.75 (m, 15H, imi-H, Ar-H). 13C{1H} NMR (DMSO-d6): δ 52.2 (d, 3JPC ) 9.2 Hz, CH2), 121.7 (imi-C), 126.1 (imi-C), 128.0 (d, 3JPC ) 9.2 Hz, Ar-C), 128.2 (d, JPC ) 11.0 Hz, Ar-C), 129.1-129.3 (overlapping signals, Ar-C), 130.6 (Ar-C), 131.0 (d, JPC ) 8.3 Hz, Ar-C), 131.1 (Ar-C), 132.0 (d, JPC ) 11.2 Hz, Ar-C), 132.3 (Ar-C), 133.4 (d, JPC ) 11.0 Hz, Ar-C), 138.0 (Ar-C), 141.7 (d, 2JPC ) 11.8 Hz, NCN); the CH3 signal is hidden under the residual peak of the solvent. Crystals of 4A suitable for X-ray crystallography were obtained by vapor diffusion of diethyl ether into a DMF solution of the solid mixture. Synthesis of PdL1I2 (5). A mixture of 2 (0.300 g, 0.619 mmol), NaOAc (0.050 g, 0.619 mmol), NaI (0.14 g, 0.930 mmol), and PdCl2 (0.109 g, 0.619 mmol) in DMF (5 mL) was heated at 70 °C for 3 h. The workup procedure follows that for 4, except that diethyl ether (2 × 15 mL) was used for product washing. A brownish solid was obtained. Yield: 0.306 g, 69%. Mp: 252 °C. Anal. Calcd for C23H21N2PI2Pd: C, 38.55; H, 2.95; N, 3.91. Found: C, 38.81; H, 3.05; N, 4.14. 1H NMR (CDCl3): δ 3.07 (s, 3H, NCH3), 5.00 (d, 2 JHH ) 15.0 Hz, 1H, NCHAHB), 6.67 (s, 1H, imi-H), 6.86-6.95 (m, 2H, NCHAHB, Ar-H), 7.12 (s, 1H, imi-H), 7.12-7.64 (m, 13H, Ar-H). 13C{1H} NMR (DMSO-d6): δ 37.8 (CH3), 52.5 (d, 3JPC ) 7.6 Hz, CH2), 122.0 (imi-C), 126.5 (imi-C), 128.2 (d, JPC ) 11.4 Hz, Ar-C), 128.8-129.4 (overlapping signals, Ar-C), 129.5 (d, JPC ) 10.6 Hz, Ar-C), 130.1 (d, 1JPC ) 35.2 Hz, Ar-C), 131.4 (Ar-C), 132.4 (d, JPC ) 11.5 Hz, Ar-C), 132.6 (Ar-C), 133.6 (d, JPC ) 10.4 Hz, Ar-C), 138.0 (Ar-C), 142.3 (d, 2JPC ) 11.6 Hz, NCN). 31 P{1H} NMR (CDCl3): δ 8.6. ESI-MS (DMF): m/z 661.7 [M - I + DMF]+. Crystals suitable for X-ray crystallography were obtained by vapor diffusion of diethyl ether into a DMF solution of the solid. Reaction between PdCl2, L2H · I, and NaOAc. A mixture of 3 (0.300 g, 0.604 mmol), NaOAc (0.055 g, 0.670 mmol), and PdCl2 (0.110 g, 0.620 mmol) in DMF (7.5 mL) was heated at 110 °C for 1.5 h. After cooling, the solvent was removed completely under vacuum. The residue was washed with water (15 mL) and extracted with dichloromethane (15 mL). The organic layer was dried with

Organometallics, Vol. 28, No. 9, 2009 2845 anhydrous MgSO4. After filtration, the solvent was removed completely under vacuum. The residue was dissolved in a minimum volume of dichloromethane. Upon slow addition of diethyl ether (25 mL), a brown precipitate was formed. The solid was filtered on a frit, washed with hexane, and dried under vacuum. A mixture of PdL2ClI (6), PdL2Cl2 (7), and PdL2I2 (8) was obtained. Yield: 0.310 g. 31P{1H} NMR (CDCl3): δ 17.4 (6), 21.3 (8), 26.1 (7). The integration ratio is 64:18:18. Few crystals of 6 suitable for X-ray structural analysis were obtained from vapor diffusion of diethyl ether into a DMF solution of the solid mixture. Attempts to isolate each compound in pure forms were unsuccessful. Synthesis of PdL2Cl2 (7). In the reaction between PdCl2, L2H · I, and NaOAc mentioned above, the use of a slight excess of PdCl2 led to a similar product mixture of 6, 7, and 8, from which a few crystals of 7 suitable for structural determination were obtained by vapor diffusion using the diethyl ether/DMF solvent combination. Attempts to separate 7 in sufficient quantity were unsuccessful. 31 P{1H} NMR (CDCl3): δ 26.1. Synthesis of PdL2I2 (8). A mixture of 3 (0.200 g, 0.403 mmol), NaOAc (0.0360 g, 0.443 mmol), NaI (0.181 g, 1.21 mmol), and PdCl2 (0.0715 g, 0.403 mmol) in DMF (7 mL) was heated at 110 °C for 1.5 h. The workup procedure is identical to that for 6. Yield: 0.206 g, 70%. Mp: 330 °C. Anal. Calcd for C23H33N2I2PPd: C, 37.91; H, 4.56; N, 3.84. Found: C, 37.69; H, 4.76; N, 3.95. 1H NMR (CD2Cl2): δ 0.31-0.39 (m, 1H, Cy-H), 0.75-0.87 (m, 2H, Cy-H), 1.06-1.78 (m, 13H, Cy-H), 1.92-2.06 (m, 2H, Cy-H), 2.22-2.33 (m, 2H, Cy-H), 2.52 (br t, 1H, PCH), 3.71 (br t, 1H, PCH), 3.83 (s, 3H, CH3), 4.66 (d, 1H, 2JHH ) 14.2, CHaHb), 6.43 (d, 1H, 2JHH ) 14.2, CHaHb), 6.83 (s, 1H, imi-H), 6.91 (s, 1H, imi-H), 7.36-7.41 (m, 4H, Ar-H). 13C{1H} NMR (CD2Cl2): δ 26.15 (Cy-C), 26.32 (Cy-C), 26.42 (d, JPC ) 20.1 Hz, Cy-C), 26.49 (d, JPC ) 8.6 Hz, Cy-C), 27.03 (d, JPC ) 12.8 Hz, Cy-C), 27.24 (d, JPC ) 13.4 Hz, Cy-C), 27.79 (d, JPC ) 8.6 Hz, Cy-C), 28.70 (CyC), 29.43 (Cy-C), 32.14 (Cy-C), 33.54 (d, 1JPC ) 23.2 Hz, PCH), 39.85 (d, 1JPC ) 25.5 Hz, PCH), 40.30 (CH3), 54.77 (d, 3JPC ) 7.8 Hz, CH2), 120.80 (imi-C), 124.71 (1JPC ) 32.9 Hz, Ar-C), 125.61 (imi-C), 128.64 (d, 3JPC ) 5.6 Hz, Ar-C), 130.48 (d, 3JPC ) 6.8 Hz, Ar-C), 131.74 (Ar-C), 134.19 (Ar-C), 143.00 (unresolved d, Ar-C), 157.60 (NCN). 31P{1H} NMR (CD2Cl2): δ 21.7. ESI-MS (DMF): m/z 602.4 [M - I + H]+. Crystals suitable for X-ray crystallography were obtained by vapor diffusion of diethyl ether into a CHCl3 solution of the solid. Synthesis of [PdL1(CH3CtN)2](BF4)2 (9). A mixture of 5 (0.363 g, 0.506 mmol) and AgBF4 (0.197 g, 1.01 mmol) in acetonitrile (15 mL) was stirred in the dark overnight. The solvent was then completely removed under vacuum. The residue was redissolved in dichloromethane, and the mixture was passed thought a plug of Celite. The volume of the solvent was reduced to ca. 3 mL, and upon addition of diethyl ether, a white solid was formed. It was then filtered and dried under vacuum. Yield: 0.280 g, 77%. Mp: 122 °C. Anal. Calcd for C27H27B2N4PF8Pd: C, 45.13; H, 3.79; N, 7.80. Found: C, 45.23; H, 3.81; N, 7.82. 1H NMR (CD3OD): δ 2.02 (br s, 6H, NtCCH3), 3.32 (s, 3H, NCH3), 5.48 (d, 2JHH ) 15.3 Hz, 1H, CHAHB), 6.92 (d, 2JHH ) 15.3, 1H, CHAHB), 7.02-7.10 (m, 1H, Ar-H), 7.17 (d, 3JHH ) 1.8 Hz, 1H, imi-H), 7.34-7.89 (m, 14H, imi-H, Ar-H). 13C{1H} NMR (CD3OD): δ 1.08 (NCCH3), 36.9 (NCH3), 53.8 (d, 3JPC ) 7.3 Hz, CH2), 119.5 (NCCH3), 124.8 (imi-C), 127.9 (Ar-C), 128.2 (imi-C), 131.1 (d, JPC ) 12.0 Hz, Ar-C), 130.7 (d, JPC ) 10.6 Hz, Ar-C), 130.4 (d, JPC ) 12.2 Hz, Ar-C), 132.5 (d, JPC ) 9.0 Hz, Ar-C), 134.0 (ArC), 133.8 (d, JPC ) 8.3 Hz, Ar-C), 134.6 (d, JPC ) 10.9 Hz, Ar-C), 135.1 (Ar-C), 138.2 (d, JPC ) 5.3 Hz, Ar-C), 142.6 (d, 2JPC ) 9.6 Hz, NCN). 31P{1H} NMR (CD3OD): δ 12.7. IR (KBr disk, cm-1): 2328 (s, CtN), 2296 (s, CtN). Synthesis of [PdL2(CH3C′N)2](BF4)2 (10). A mixture of 8 (0.250 g, 0.343 mmol) and AgBF4 (0.134 g 0.686 mmol) in acetonitrile (15 mL) was stirred in the dark overnight. The solvent was then

2846 Organometallics, Vol. 28, No. 9, 2009 removed completely under vacuum. The residue was redissolved in dichloromethane, and the mixture was passed thought a plug of Celite. The solvent was removed completely again under vacuum. The off-white solid was washed with hexane (5 mL) and dried under vacuum. Yield: 0.200 g, 80%. Mp: 130 °C. Anal. Calcd for C27H39B2F8N4PPd: C, 44.39; H, 5.38; N, 7.67. Found: C, 44.26; H, 5.32; N, 7.70. 1H NMR (CD3OD): δ 0.81-2.04 (m, 25H, Cy-H, CH3CN), 2.45-2.54 (m, 3H, Cy-H), 5.12 (d, 1H, 2JHH ) 14.7, CHH), 6.24 (d, 1H, 2JHH ) 14.7, CHH), 7.24 (s, 1H, imi-H), 7.43 (s, 1H, imi-H), 7.46-7.61 (m, 4H, Ar-H). 13C{1H} NMR (CD3OD): δ 25.0-26.4 (overlapping signals, Cy-C), 28.0 (Cy-C), 28.8 (CyC), 30.2 (d, 3JPC ) 3.0 Hz, Cy-C), 32.3 (d, 1JPC ) 30.1 Hz, PCH), 33.9-34.9 (br, CH3CN), 36.4 (CH3), 53.3 (d, 3JPC ) 7.7 Hz, CH2), 119.5 (d, 1JPC ) 48.0 Hz, PC), 122.9 (imi-C), 126.7 (imi-C), 129.0 (d, 3JPC ) 8.5 Hz, Ar-C), 130.8 (d, 3JPC ) 7.8 Hz, Ar-C), 133.0 (d, 4 JPC ) 2.2 Hz, Ar-C), 133.9 (d, 2JPC ) 2.6 Hz, Ar-C), 140.5 (br, Ar-C), 142.0 (d, 2JPC ) 10.7 Hz, NCN). The peak due to the CH3CN was not located. 31P{1H} NMR (CD3OD): δ 36.1. IR (KBr disk, cm-1): 2327 (s, CtN), 2301 (s, CtN). Synthesis of [PdL1(py)2](BF4)2 (11). A mixture of 5 (0.294 g, 0.411 mmol) and AgBF4 (0.160 g, 0.822 mmol) in pyridine (10 mL) was stirred in the dark overnight. The solvent was then completely removed under vacuum. The residue was redissolved in DMF, and the mixture was passed thought a plug of Celite. The solvent was again removed under vacuum. The residue was redissolved in a minimum amount of dichloromethane, and upon addition of diethyl ether, a pale yellow solid was formed. It was then filtered and dried under vacuum. Yield: 0.210 g, 65%. Mp: 291-310 °C. Anal. Calcd for C33H31B2N4PF8Pd · 2H2O: C, 47.71; H, 4.25; N, 6.74. Found: C, 47.26; H, 4.32; N, 6.64. 1H NMR (DMSO-d6): δ 3.25 (s, 3H, NCH3), 5.58 (d, 2JHH ) 15.0 Hz, 1H, CHAHB), 6.91-8.89 (m, 23H, CHAHB, imi-H, Ar-H, PyH), 8.89 (br s, 2H, py-H), 9.16 (d, 3JHH ) 5.1 Hz, 2H, py-H). 13 C{1H} NMR (DMSO-d6): δ 35.9 (NCH3), 52.7 (CH2), 123.5 (imi-C), 124.3 (d, 1JHH ) 54.6 Hz, PC), 125.7-126.3 (overlapping signals), 126.6 (d, JPC ) 10.9 Hz, Py-C or Ar-C), 128.73 (d, JPC ) 11.3 Hz, Py-C or Ar-C), 129.4 (d, JPC ) 11.2 Hz, Py-C or Ar-C), 131.2 (Py-C or Ar-C), 131.6 (d, JPC ) 14.0 Hz, Py-C or Ar-C), 131.7(d, JPC ) 10.6 Hz, Py-C or Ar-C), 132.4 (Ar-C), 132.8 (d, JPC ) 11.8 Hz, Py-C or Ar-C), 133.5 (Ar-C), 137.0 (Py-C or Ar-C), 139.6 (Py-C or Ar-C), 141.6 (d, 2JPC ) 10.7 Hz, Ar-C), 147.5 (d, 2JPC ) 15.8 Hz, NCN), 151.0 (Py-C). 31 P{1H} NMR (DMSO-d6): δ 9.3. Crystals of [PdL1(py)2](BF4)2 (11) were obtained by vapor diffusion of diethyl ether into a pyridine solution of [PdL1(CH3CtN)2](BF4)2 (9). Synthesis of [PdL2(py)2](BF4)2 (12). The compound was prepared using a similar procedure to that described for 11. A mixture of 8 (0.422 g, 0.578 mmol) and AgBF4 (0.226 g 1.16 mmol) in pyridine (10 mL) was used. Yield: 0.282 g, 61%. Mp: 272-285 °C. Anal. Calcd for C33H43B2F8N4PPd · 0.5H2O: C, 48.05; H, 5.50; N, 6.79. Found: C, 47.82; H, 5.74; N, 6.31. 1H NMR (DMSO-d6): δ 0.37 (br s, 2H, Cy-H), 0.76-2.03 (m, 17H, Cy-H), 2.31 (br t, 1H, Cy-H), 2.65 (br s, 2H, Cy-H), 3.84 (CH3), 5.38 (d, 1H, 2JHH ) 15.0 Hz, CHaHb), 7.12 (d, 1H, 2JHH ) 15.0 Hz, CHaHb), 7.35 (s, 1H, imi-H), 7.46-7.95 (m, 11H, Ar-H, Py-H, imi-H), 8.14 (t, 1H, 2 JHH ) 7.2 Hz, Py-H), 9.16 (d, 2JHH ) 5.3 Hz, 1H, Py-H), 9.31 (d, 2 JHH ) 5.3 Hz, 2H, Py-H). 13C{1H} NMR (DMSO-d6): δ 25.1-26.1 (overlapping signals, Cy-H), 27.1 (Cy-H), 27.9 (Cy-H), 29.4 (s, Cy-C), 32.8 (d, 1JPC ) 28.8 Hz, PCH), 35.8 (d, 1JPC ) 24.5 Hz, PCH), 37.0 (CH3), 53.0 (d, 3JPC ) 7.6 Hz, CH2), 121.9 (d, 1JPC ) 44.1 Hz, PC), 123.0 (imi-C), 126.5 (imi-C), 127.3 (Py-C), 129.1 (d, 3JPC ) 7.8 Hz, Ar-C), 131.1 (d, 3JPC ) 7.7 Hz, Ar-C), 133.8 (Ar-C), 132.7 (Ar-C), 140.8 (Py-C), 142.1 (d, 2JPC ) 7.8 Hz, ArC), 146.5 (d, 2JPC ) 14.0 Hz, NCN), 151.0 (Py-C). 31P{1H} NMR (DMSO-d6): δ 20.3. Crystals of [PdL2(py)2](BF4)2 (12) were obtained by vapor diffusion of diethyl ether into a pyridine solution of [PdL2(CH3CtN)2](BF4)2 (10).

Ho et al. X-ray Data Collection. Typically, the crystals were removed from the vial with a small amount of mother liquor and immediately coated with paratone-N oil on a glass slide. A suitable crystal was mounted on a glass fiber with silicone grease and placed in the cold stream of a Bruker APEX II equipped with as CCD area detector and a graphite monochromator utilizing Mo KR radiation (λ ) 0.71073 Å) at 150(2) K. The data were corrected for Lorentz and polarization effects using the Bruker SAINT software, and an absorption correction was performed using the SADABS program.56 Solution and Structure Refinements. All the structures were solved by direct methods and refined by full-matrix least-squares methods against F2 with the SHELXTL software package.57 All non-H atoms were refined anisotropically; H-atoms were fixed at calculated positions and refined with the use of a riding model. Crystallographic data are listed in Table 1. There are two independent molecules in the asymmetric unit of 4A, only one of which is used for structural discussion. The disordered solvent molecules in the voids of 7 were not located. CCDC-703250 (4a), -703251 (5), -703252 (6), -703253 (7), -703254 (8), -703255 (11), and -706671 (12) contain the supplementary crystallographic data for this paper. These data can obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/ data_request/cif. Suzuki Coupling Reactions with Conventional Heating. In a typical reaction, a mixture of aryl bromides (1.0 mmol), phenylboronic acid (1.5 mmol), Cs2CO3 (2.6 mmol), and palladium(II) precatalyst (3 mol %) in 3 mL of 1,4-dioxane was stirred at 80 °C for 2 h under nitrogen. The solution was allowed to cool to ambient temperature for GC analysis. GC yields were calculated using benzophenone as internal standards. In the standard workup, the solvent was removed completely under vacuum. A 1:1 mixture of diethyl ether/water (20 mL) was added. The organic layer was washed, separated, further washed with another 10 mL portion of diethyl ether, and dried with anhydrous MgSO4. The solution was then filtered. The solvent and any volatiles were removed completely under high vacuum to give a crude product, which was subject to flash chromatography. Suzuki Coupling Reactions under Microwave Irradiations. In a typical reaction, a mixture of aryl bromides (1.0 mmol), phenylboronic acid (1.5 mmol), Cs2CO3 (2.6 mmol), and palladium(II) precatalyst (3 mol %) in 2.5 mL DMF/0.5 mL H2O was irradiated and stirred at 150 °C for 15 min in an Milestone Start S microwave system. Reaction times refer to hold times at the temperature indicated. The temperature was measured with an IR sensor on the outside of the reaction vessel. The workup procedure is similar to that with conventional heating. Preparation of Felbinac. The preparation followed the typical procedures with conventional heating and microwave irradiation. After the reaction, water (50 mL) was added and the mixture was filtered through a small plug of Celite. The aqueous layer was washed with ethyl acetate (2 × 25 mL). After separation, the aqueous layer was acidified with dilute HCl. Dichloromethane (50 mL) was added to extract the compound. After separation, the organic layer was dried with anhydrous MgSO4. The solvent was then removed completely under vacuum to afford the white solid of felbinac. Direct Arylation for the Formation of 9-Benzylidene-9Hfluorene. In a typical reaction, a mixture of phenyl halides (1.0 mmol), diphenylacetylene (1.0 mmol), NaOAc (2.0 mmol), and palladium(II) precatalyst (5 mol %) in 5 mL of DMF was stirred at the temperature and for the period of time indicated in Table 4. In the standard workup, the reaction mixture was allowed to cool to ambient temperature, diluted with diethyl ether, washed with brine, and dried with anhydrous MgSO4. The solution was (56) Sheldrick, G. M. SADABS; University of Go¨ttingen: Germany, 2001. (57) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.

Direct Arylation Mediated by Palladium Complexes then filtered. The solvent and any volatiles were removed completely under high vacuum to give a crude product, which was purified by column chromatography.

Acknowledgment. We are grateful to the National Science Council of Taiwan for financial support of this work. We also thank the National Center for HighPerformance Computing of Taiwan for financial support of the Conquest software.

Organometallics, Vol. 28, No. 9, 2009 2847 Supporting Information Available: Full crystallographic data for all the structures are provided as a CIF file. A 1H NMR spectrum of 8. A perspective drawing of 5. This material is available free of charge via the Internet at http://pubs. acs.org.

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