Suzuki-Miyaura Coupling Reaction of Aryl Chlorides Using Di(2,6-dimethylmorpholino)phenylphosphine as Ligand PDF

Tetrahedron 63 (2007) 1345–1352 Suzuki–Miyaura coupling reaction of aryl chlorides using di(2,6-dimethylmorpholino)phenylphosphine as ligand Su-Dong Cho,a Ho-Kyun Kim,b Heung-seop Yim,b Mi-Ra Kim,c Jin-Kook Lee,a,* Jeum-Jong Kimd and Yong-Jin Y...

Tetrahedron 63 (2007) 1345–1352 Suzuki–Miyaura coupling reaction of aryl chlorides using di(2,6-dimethylmorpholino)phenylphosphine as ligand Su-Dong Cho,a Ho-Kyun Kim,b Heung-seop Yim,b Mi-Ra Kim,c Jin-Kook Lee,a,* Jeum-Jong Kimd and Yong-Jin Yoond,* a Department of Polymer Science and Engineering, Pusan National University, Busan 609-735, Republic of Korea b Department of Chemistry and Graduate School for Molecular Materials and Nanochemistry, Gyeongsang National University, Jinju 660-701, Republic of Korea c Center for Plastic Information System, Pusan National University, Busan 609-735, Republic of Korea d Department of Chemistry and Environmental Biotechnology National Core Research Center, Graduate School for Molecular Materials and Nanochemistry, Gyeongsang National University, Jinju 660-701, Republic of Korea Received 9 June 2006; revised 30 November 2006; accepted 4 December 2006 Abstract—Suzuki–Miyaura coupling was achieved on a variety of aryl chlorides by using di(2,6-dimethylmorpholino)phenylphosphine (L1) as a bulky electron-rich monoaryl phosphine ligand. We report the couplings of various chlorobenzenes and heteroaryl chlorides. Ó 2006 Elsevier Ltd. All rights reserved. 1. Introduction ferrocenyldialkylphosphine,17 aryldialkylphosphine,36–38 phosphinous acid,39 palladacycle,15,40 or heterocyclic carb- Pd-catalyzed cross-coupling reactions have become an ex- ene41–43 classes have been investigated for these reactions. tremely versatile tool in organic synthesis for connecting While several ligands exhibiting improved abilities in assist- two fragments via formation of a carbon–carbon bond or ing the palladium-catalyzed coupling are now available, carbon–heteroatom bond.1–4 The Pd-catalyzed Suzuki– a general solution has not yet been completely found for Miyaura coupling reaction is one of the most attractive the metal-catalyzed aryl coupling of all substrates. Thus, method for preparing biaryl compounds thanks to the advan- as a part of our ongoing efforts to develop efficient methods tages of wide functional group tolerance and use of stable for the coupling of aryl chloride, we investigated the synthe- and nontoxic organoborane reagents.5–13 Since the general sis and coupling reaction of novel air stable phenyl back- procedures were discovered, efforts have been made toward bone-derived PN2 ligands that are easy to prepare. The in increasing the substrate scope and efficiency. Although reaction setup is experimentally simple and does not require the use of alternative bases or solvents can be beneficial, the use of a glovebox for these reactions. electronic and steric tuning of the supporting ligand has the most impact on increasing efficacy and reactivity in these We used ligands 1–4 for the Suzuki–Miyaura coupling of aryl processes.14–29 A major impetus to this field was provided by chlorides as monophenyl backbone-derived PN2 ligands the ability to activate the notoriously unreactive but rela- (Scheme 1). Ligand 4 is commercially available, and ligands tively cheap aryl chlorides.30 Not surprisingly, a plethora 2 and 3 were prepared by the literature method.44 The of Pd-catalyst systems featuring a Pd-bound ligand are ligand 1 was synthesized from dichlorophenylphosphine (5) now accessible for achieving the aforementioned transfor- (Scheme 2). Here, we report the results of coupling aryl chlo- mation involving aryl chlorides. It has been well recognized ride with phenylboronic acid by using novel PN2 ligands. that ligands employed in these processes have a significant impact on the outcome of the reactions.31,32 Therefore, de- O O signing ligands with appropriate features and great diversity N N N N is crucial in dealing with the challenging substrates in this P P P P area. Typically, the electronically rich and sterically hin- N N N N dered ligands belonging to the trialkylphosphine,33–35 O O Keywords: Suzuki–Miyaura coupling; Pd-catalyzed coupling of aryl chlo- 1 2 3 4 rides; PN2 ligand; C–C coupling reaction. * Corresponding authors. Tel.: +82 55 751 6019; fax: +82 55 761 0244; Scheme 1. Bulky electron-rich ligands used in the coupling of aryl e-mail: [email protected] chlorides. 0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2006.12.001 1346 S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 Cl TEA, CH2Cl2 NRR' Table 2. Screening of Pd-catalystsa P + HNRR' P Pd-catalyst, ligand 1, 0 °C to reflux Cl NRR' Cl B(OH)2 Cs2CO3 5 N N + 1,4-Dioxane, reflux NC -NRR' = N NC O O 1 2 3 Entry Palladium catalyst Time (min) Productb (%) Scheme 2. Syntheses of ligands 1, 2, and 3. 1 Pd2(dba)3 90 95 2c PdCl2 90 91 3c Pd(OAc)2 125 84 2. Results and discussion 4c Pd(PPh3)4 80 92 5c PdCl2(PPh3)2 80 92 6c PdCl2(dppf)2 100 83 2.1. Synthesis of ligand 1 7c Pd/C 16 h 32 8d Pd2(dba)3 3h — Reaction of dichlorophenylphosphine (5) with 2,6-dimethyl- a Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic morpholin (6) in the presence of triethylamine in refluxing acid (1.25 equiv), ligand 1 (10 mol %), Pd-catalyst (1 mol %), Cs2CO3 dichloromethane or toluene gave the corresponding ligand (2 equiv), and 1,4-dioxane (20 mL) at reflux temperature. 1 (68%). This ligand in coupling reaction was used without b Isolated yield after silica gel chromatography. c further purification. The structure of ligand 1 was estab- d Self-coupling product from boronic acid was isolated in small amounts. lished by IR, NMR, and elemental analysis. Coupling reaction was carried out in the absence of ligand 1. 2.2. Ligand, Pd-catalyst, solvent, and base screening Table 3. Screening of basesa Pd2(dba)3, ligand 1, To test the feasibility of the ideas described above, we Cl B(OH)2 Base initially conducted the reaction of p-cyanochlorobenzene + NC 1,4-Dioxane, reflux with phenylboronic acid in refluxing 1,4-dioxane as shown NC in Table 1. We used 1.0 mol % of Pd(OAc)2 in combination with 5 mol % of ligand 1. This reaction proceeded to Entry Base Time (h) Isolated yield (%) successfully afford the desired product in 91% isolated yield 1 t-BuOK 3.5 88 after 1.5 h (Entry 1 in Table 1). With this encouraging result, 2 Cs2CO3 1 96 we evaluated the efficiency of the three ligands 2–4 in the 3 K3PO4 1.5 87 4 K2CO3 51 63 same screening. When ligand 2 was used, the product gave 5 Rb2CO3 1 90 a 74% yield. This reaction, however, did not occur when 6 KF 36 36 ligands 3 and 4 were used. 7 DMAP 36 25 a Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic Next, we investigated the effect of a variety of palladium acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), base compounds for this reaction. Among the palladium com- (4.2 mmol, 2.1 equiv), and 1,4-dioxane (20 mL) at reflux temperature. pounds explored, Pd2(dba)3 showed the best result (Entry 1 in Table 2). The coupling reaction, however, did not occur in the absence of ligand 1 under same condition (Entry 8 yield (Entries 2 and 5 in Table 3). According to the litera- in Table 2). tures,45–47 cesium carbonate is a very effective base for most Pd-catalyzed coupling procedures using phosphine We also investigated a variety of bases for the aforemen- ligand. We investigated some solvents for coupling reaction tioned coupling reaction catalyzed by the Pd2(dba)3/1 catalyzed by the Pd2(dba)3/1/Cs2CO3 system (Table 4). system (Table 3). The coupling reaction of chlorocyanobenz- Toluene and 1,4-dioxane were found to be an efficacious ene by using Pd2(dba)3/1 system in the presence of Cs2CO3 solvent (Entries 1 and 4 in Table 4). In general, nonpolar or Rb2CO3 gave biphenyl-4-carbonitrile in 96% or 90% hydrocarbon (toluene) and ethereal solvent (1,4-dioxane) are useful solvents in Pd-catalyzed coupling reactions.48 Table 1. Screening of ligandsa Table 4. Screening of solventsa Pd(OAc)2, ligand, Pd2(dba)3, ligand 1, Cl B(OH)2 t-BuOK Cl B(OH)2 Cs2CO3 + NC + NC 1,4-Dioxane, reflux Solvent, reflux NC NC Entry Ligand Time (h) Productb (%) Entry Solvent Time (h) Isolated yield (%) 1 1 1.5 91 1 Toluene 1 95 2 2 18 74 2 Acetonitrile 2 94 3 3 24 No reaction 3 Ethanol 4 85 4 4 24 No reaction 4 1,4-Dioxane 1 96 a 5 Tetrahydrofuran 2 83 Reaction conditions: chlorocyanobenzene (2.0 mmol, 1.0 equiv), phenyl- 6 Water 24 14 boronic acid (2.5 mmol, 1.25 equiv), ligand (5 mol %), Pd(OAc)2 a (1 mol %), t-BuOK (4.2 mmol, 2.1 equiv), and 1,4-dioxane (20 mL) at Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic reflux temperature. acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 b Isolated yield after silica gel chromatography. (2 equiv), and solvent (20 mL) at reflux temperature.  S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 1347 Table 5. Optimization for the coupling of chlorocyanobenzene with phenyl- boronic acid using 1a Table 6. Pd-catalyzed coupling of aryl chloridesa Pd2(dba)3, ligand 1, Pd2(dba)3, 1 Cl B(OH)2 Cs2CO3 NC B(OH)2 Cs2CO3 + 1,4-Dioxane, reflux Ar Ar-Cl + 1,4-Dioxane, reflux NC Entry 1 (mol %) Pd2(dba)3 (mol %) Time (h) Yieldb (%) Entry Aryl chloride Time (h) Product yieldb (%) 1 1 0.5 62 82 2 2 1 43 89 1 MeO Cl 14 MeO (77) 3 5 1 13 92 4 10 1 1 96 5 10 2 1 95 OMe OMe a 2 10 (75) Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic Cl acid (1.25 equiv), ligand 1 (1–10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 (2 equiv), and 1,4-dioxane (20 mL) at reflux temperature. MeO MeO b Isolated yield after silica gel chromatography. 3 7 (70) Cl We optimized the coupling of chlorocyanobenzene with phenylboronic acid by using the Cs2CO3/Pd2(dba)3/1 system in 1,4-dioxane (Table 5). The ArCl (1 equiv)/ArB(OH)2 4 Cl 22 (81) (1.25 equiv)/Cs2CO3 (2 equiv)/Pd2(dba)3 (1 mol %)/1 (10 mol %) system in 1,4-dioxane showed the best result (Entry 4 in Table 5). 5 26 (78) MeHN Cl MeHN Applying the conditions optimized in this research, we eval- uated the scope of the coupling of various aryl and heteroaryl chlorides with phenylboronic acid. The coupling of chloro- 6 H2N Cl 1.5 H2 N (78) benzene containing various substituents with phenylboronic acid by using Cs2CO3 (2 equiv)/Pd2(dba)3 (1 mol %)/1 O2 N O2 N (10 mol %) system in 1,4-dioxane gave the corresponding 7 14 (72) biphenyls in good to excellent yields (Table 6). The coupling Me Cl Me of chlorobenzenes did not show the general tendency that depended on the kind of substituents in phenyl ring. 8 Cl 16 (96) O O On the other hand, the coupling of chloroheteoarenes such as 2-chloropyridine, 2-chlorothiophene, 2-chloropyrimidine, 4-chloropyridazin-3(2H)-one, 4-chlorotetrazole, 2-chloroqui- 9 NC Cl 15 NC (93) noline, and 2-chlorothioxanthen-9-one with phenylboronic acid under our system gave the corresponding phenyl- substituted products in good to excellent yields (Table 7). 10 PhO2S Cl 12 PhO2S (97) We also investigated the coupling of chlorocyanobenzene with some arylboronic acids by using the system we devel- oped (Table 8). The homo-coupling of phenylboronic acids was predominant when phenylboronic acids containing the 11 OHC Cl 10 OHC (87) electron-withdrawing groups such as chloro, formyl, and nitro substituents were used (Entries 1, 4, and 5 in Table 8). However, the cross-coupling of chlorocyanobenzene was 12 MeO2C Cl 18 MeO2C (90) predominant when 4-methoxy and 4-(N,N-dimethylamino)- phenylboronic acids were used (Entries 2 and 3 in Table 8). The self-coupling products from the corresponding boronic 13 O2 N Cl 14 O2 N (94) acids on TLC were not detected by the coupling of chloro- cyanobenzene with 2-furanboronic acid and 4-pyridine- Cl boronic acid. 14 7 (98) 3. Conclusion In conclusion, we developed ligand 1 as a new PN2 ligand for a Reaction conditions: ArCl (1.0 equiv), phenylboronic acid (1.25 equiv), Pd-catalyzed Suzuki–Miyaura coupling of aryl chlorides ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 (2 equiv), and 1,4- with phenylboronic acids. This ligand 1 also has the follow- dioxane (20 mL) at reflux temperature. b ing advantages: as an efficient ligand for Pd-catalyzed cross- Isolated yield after silica gel chromatography. coupling of aryl chlorides, it is stable in air and in organic 1348 S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 Table 7. Pd-catalyzed coupling of heteroaryl chloridesa Pd2(dba)3,1 B(OH)2 Cs2CO3 Ar-Cl + Ar 1,4-Dioxane, reflux Entry Aryl chloride Time (h) Product yieldb (%) OEt OEt 1 3 (96) Cl N N S Cl S 2 15 (38) N N 3 Cl 7 (70) N N OEt OEt 4 N Cl 1.5 N (95) N N Et O Et O 5 6 N (93) N MeO N MeO N Cl Cl 6 N 7 (72) N N N N N N N N N 7 Cl 2 (96) O O Cl 8 8 (95) S S a Reaction conditions: ArCl (1.0 equiv), phenylboronic acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 (2 equiv), and 1,4-dioxane (20 mL) at reflux temperature. b Isolated yield after silica gel chromatography. solvents at high temperature, and easily prepared from cheap 4.2. Typical preparation of PN2 ligands and commercially available dichlorophenylphosphine. A mixture of 2,6-dimethylmorpholine (2 equiv), triethyl- 4. Experimental amine (2.2 equiv), and dichloromethane (50 mL) was stirred for 10 min at room temperature. A dichloromethane solution 4.1. General of dichlorophenylphosphine 5 (20 mmol of 5 in 200 mL dichloromethane) was slowly dropped to the above amine Melting points were determined with a capillary apparatus solution, and the mixture was refluxed for 24 h until phos- and are uncorrected. 1H and 13C NMR spectra were recorded phine 5 disappeared. After evaporating the solvent under on a 300 MHz spectrometer with the chemical shift values reduced pressure, the resulting residue was triturated in reported in d units (ppm) relative to an internal standard n-hexane, filtered, and washed with n-hexane. The filtrates (TMS). The IR spectra were obtained on an IR spectropho- containing the product were combined and evaporated under tometer. Elemental analyses were performed with a Perkin– reduced pressure. The resulting residue was applied to Elmer 240C. The open-bed chromatography was carried out the top of an open-bed silica gel column (3.07 cm). The on silica gel (70w230 mesh, Merck) using gravity flow. The column was eluted with dichloromethane/diethyl ether column was packed with slurries made from the elution (10/1, v/v). Fractions containing the product were com- solvent. bined and evaporated under reduced pressure to give  S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 1349 Table 8. Pd-catalyzed coupling of aryl chlorides with some phenylboronic was purified by chromatography on silica gel using dichloro- acidsa methane/n-hexane (1:2, v/v) to afford the coupled product. Pd2(dba)3,1 Cl Cs2CO3 Ar-B(OH)2 + 1,4-Dioxane, reflux Ar CN 4.3.1. Biphenyl. Mp 68–71  C (lit.49 mp 68–70  C); IR (po- NC tassium bromide) n 3008, 2986, 1602, 1424 cm1; 1H NMR (CDCl3) d 7.18–7.65 (m, 10H) ppm; 13C NMR (CDCl3) Entry Boronic acid Time Product yieldb (%) d 127.23, 127.31, 128.81, 141.32 ppm. Elemental analysis (h) calcd for C12H10: C, 93.46; H, 6.54. Found: C, 93.51; H 6.60. 1c Cl B(OH)2 36 Cl CN (—) 4.3.2. Biphenyl-4-carbonitrile. Mp 85–87  C, IR (potas- sium bromide) n 3012, 2984, 2224, 1432 cm1; 1H NMR (CDCl3) d 7.24–7.66 (m, 9H) ppm; 13C NMR (CDCl3) 2d MeO B(OH)2 6 MeO CN (92) d 110.80, 118.95, 127.22, 127.70, 128.72, 129.16, 132.59, 139, 145.56 ppm. Elemental analysis calcd for C13H9N: C, 87.12; H, 5.06; N, 7.82. Found: C, 87.17; H, 5.11; N, 7.88. 3d (Me)2N B(OH)2 6 (Me)2N CN (90) Elemental analysis calcd for C13H9N: C, 87.12; H, 5.06; N, 7.82. Found: C, 87.20; H, 5.12; N, 7.91. 4e OHC B(OH)2 6 OHC CN (52) 4.3.3. 4-Nitrobiphenyl. Mp 113–115  C; IR (potassium bromide) n 3062, 3028, 1602, 1550, 1518, 1340 cm1; 1H B(OH)2 CN NMR (CDCl3) d 8.31–8.26 (m, 2H), 7.75–7.70 (m, 2H), 5f 24 (19) 7.63–7.60 (m, 2H), 7.52–7.41 (m, 3H) ppm; 13C NMR O2N O2N (CDCl3) d 147.63, 147.15, 138.79, 129.15, 128.91, 127.79, O O 127.38, 124.09 ppm. Elemental analysis calcd for 6g B(OH)2 40 CN (6) C12H9NO2: C, 72.35; H, 4.55; N, 7.03. Found: C, 72.40; H, 4.58; N, 7.09. 7 N B(OH)2 3 N CN (76) 4.3.4. Biphenyl-4-carboxylic acid methyl ester. Mp 115– a 117  C. IR (potassium bromide) n 3042, 2988, 1738, 1622, Reaction conditions: chlorocyanobenzene (1.0 equiv), boronic acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 1460, 1422, 1308, 1130, 764 cm1; 1H NMR (CDCl3) (2 equiv), and 1,4-dioxane (20 mL) at reflux temperature. d 8.10 (d, J¼8.4 Hz, 2H), 7.65–7.58 (m, 4H), 7.47–7.36 b c Isolated yield after silica gel chromatography. (m, 3H), 3.92 (s, 3H) ppm; 13C NMR (CDCl3) d 166.97, Only self-coupling product from boronic acid was isolated in poor yield. 145.64, 140.02, 130.11, 128.96, 128.93, 127.27, 127.04, d Self-coupling product from boronic acid was detected on TLC. e Self-coupling product from boronic acid was isolated in poor yield. 52.07 ppm. Elemental analysis calcd for C14H12O2: C, f Self-coupling product from boronic acid was isolated as the main product. 79.22; H, 5.70. Found: C, 80.2; H, 5.81. g Reaction was not proceeded completely. 4.3.5. 2-Methoxybiphenyl. Colorless oil (lit.50 mp 30– di(2,6-dimethylmorpholino)phenylphosphine (1). Ligand in 33  C); IR (potassium bromide) n 3060, 2926, 1599, 1499, coupling reaction was used without further purification. 1482, 1258, 1025 cm1; 1H NMR (CDCl3) d 7.81–7.78 (m, 2H), 7.66–7.50 (m, 5H), 7.29–7.17 (m, 2H), 3.98 (s, 4.2.1. Ligand 1. Yield: 68%. Colorless oil, IR (potassium 3H) ppm; 13C NMR (CDCl3) d 156.75, 138.86, 131.11, bromide) n 3012, 2904, 1436, 1366, 1120, 1048 cm1; 1H 131.02, 129.80, 128.84, 128.20, 127.12, 121.10, 111.57, NMR (CDCl3) d 7.81–7.30 (m, 5H), 3.87–3.78 (m, 4H), 55.70 ppm. Elemental analysis calcd for C13H12O: C, 3.51–3.44 (m, 2H), 2.99 (d, J¼12.16 Hz, 4H), 2.44–2.40 84.75; H, 6.57. Found: C, 84.79; H, 6.59. (m, 2H), 1.10 (s, CH3), 1.08 (s, CH3) ppm; 13C NMR (CDCl3) d 11.69, 47.92, 69.71, 128.15, 128.32, 126.60, 4.3.6. 3-Methoxybiphenyl. Colorless oil; IR (potassium 129.74 ppm. Elemental analysis calcd for C18H29N2O2P: bromide) n 3054, 2959, 1599, 1479, 1266, 1220 cm1; 1H C, 64.26; H, 8.69; N, 8.33. Found: C, 64.31; H, 8.71; N 8.40. NMR (CDCl3) d 7.57–7.53 (m, 2H), 7.41–7.35 (m, 2H), 7.32–7.26 (m, 2H), 7.16–7.09 (m, 2H), 6.87–6.83 (m, 1H), 4.3. Typical C–C coupling of aryl chlorides 3.78 (s, 3H) ppm; 13C NMR (CDCl3) d 160.14, 142.92, 141.25, 129.90, 128.87, 127.55, 127.32, 119.83, 113.09, A dried resealable Schlenk tube was charged with Pd2(dba)3 112.85, 55.36 ppm. Elemental analysis calcd for C13H12O: (0.03 mmol, 1 mol % of Pd), aryl chloride (2.0 mmol), C, 84.75; H, 6.57. Found: C, 84.78; H 6.61. phenylboronic acid (2.5 mmol, 1.25 equiv), and ligand 1 (10 mol %) in 1,4-dioxane (20 mL). The mixture was stirred 4.3.7. 4-Methoxybiphenyl. Mp 89–90  C (lit.50 mp 86– for 5 min at room temperature under nitrogen atmosphere. 90  C); IR (potassium bromide) n 3050, 2958, 1606, 1516, Cesium carbonate (4.2 mmol, 2.1 equiv) was added to the re- 1485, 1272, 1037 cm1; 1H NMR (CDCl3) d 7.56–7.49 action mixture. After the septum was replaced with a Teflon (m, 4H), 7.43–7.38 (m, 2H), 7.31–7.26 (m, 1H), 6.99–6.94 screwcap, the mixture was refluxed until aryl chloride had (m, 2H), 3.84 (s, 3H) ppm; 13C NMR (CDCl3) d 159.20, been completely consumed as judged by TLC. The reaction 140.87, 133.83, 128.72, 128.16, 126.75, 126.66, 114.24, mixture was then cooled to room temperature and filtered. 55.35 ppm. Elemental analysis calcd for C13H12O: C, The filtrate was concentrated in vacuo. The crude material 84.75; H, 6.57. Found: C, 84.77; H, 6.60. 1350 S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 4.3.8. 1-Biphenyl-4-ylpropan-1-one. Mp 96–98  C; IR 128.21, 127.93, 127.66, 127.34 ppm. Elemental analysis (potassium bromide) n 3048, 2982, 1680, 1600, 1218, calcd for C18H14O2S: C, 73.44; H, 4.79. Found: C, 73.50; 750 cm1; 1H NMR (CDCl3) d 8.04–8.02 (m, 2H), 7.68– H, 4.82. 7.59 (m, 4H), 7.49–7.36 (m, 3H), 3.04 (q, J¼7.26 Hz, 2H), 1.25 (t, J¼7.24 Hz, 3H) ppm; 13C NMR (CDCl3) d 200.40, 4.3.15. 9-Phenylanthracene. Mp 153–154  C (lit.52 mp 145.55, 139.97, 135.68, 128.93, 128.57, 128.16, 127.25, 153–155  C); IR (potassium bromide) n 3046, 1436, 1008, 127.20, 31.83, 8.32 ppm. Elemental analysis calcd for 870, 726, 696 cm1; 1H NMR (CDCl3) d 8.62 (br s, 1H), C15H14O: C, 85.68; H, 6.71. Found: C, 85.73; H, 6.79. 8.11–8.16 (m, 2H), 7.36–7.65 (m, 11H) ppm; 13C NMR (CDCl3) d 126.10, 126.42, 127.21, 127.54, 128.29, 129.43, 4.3.9. 40 -Methoxybiphenyl-4-carbonitrile. Mp 103– 131.02, 131.94, 132.44, 137.71, 139.62 ppm. Elemental 104  C; IR (potassium bromide) n 3038, 2988, 2220, 1602, analysis calcd for C20H14: C, 94.45; H, 5.55. Found: C, 1242, 1174, 1132, 822 cm1; 1H NMR (CDCl3) d 7.69– 94.51; H, 5.58. 7.60 (m, 4H), 7.55–7.50 (m, 2H), 7.02–6.97 (m, 2H), 3.85 (s, 3H) ppm; 13C NMR (CDCl3) d 160.27, 145.22, 4.3.16. Biphenyl-4-carbaldehyde. Mp 56–58  C (lit.49 mp 132.55, 131.51, 128.35, 127.10, 119.06, 114.59, 110.16, 57–59  C); IR (potassium bromide) n 3006, 2832, 1690, 55.40 ppm. Elemental analysis calcd for C14H11NO: C, 1592, 1200, 720 cm1; 1H NMR (CDCl3) d 10.05 (s, 1H), 80.36; H, 5.30; N, 6.69. Found: C, 80.41; H, 5.37; N, 6.71. 7.96–7.92 (m, 2H), 7.76–7.73 (m, 2H), 7.65–7.61 (m, 2H), 7.50–7.38 (m, 3H), 5.25 (d, J¼10.88 Hz, 1H), 2.83 (s, 4.3.10. 1,5-Diphenyl-1H-tetrazole. Mp 144–145  C; IR 3H) ppm; 13C NMR (CDCl3) d 191.83, 147.21, 139.75, (potassium bromide) n 3070, 1590, 1495, 1470, 1110, 760, 135.26, 130.25, 129.01, 128.47, 127.69, 127.37 ppm. Ele- 696 cm1; 1H NMR (CDCl3) d 7.82–7.78 (m, 2H), 7.61– mental analysis calcd for C13H10O: C, 85.69; H, 5.53. 7.39 (m, 7H), 7.33–7.25 (m, 1H) ppm; 13C NMR (CDCl3) Found: C, 85.72; H, 5.55. d 159.41, 153.53, 133.17, 130.04, 129.75, 129.46, 126.53, 122.22, 119.37 ppm. Elemental analysis calcd for 4.3.17. 3-Ethoxy-2-phenylpyridine. Colorless oil; IR C13H10N4: C, 70.26; H, 4.54; N, 25.21. Found: C, 70.30; (potassium bromide) n 3053, 2974, 1628, 1444, 1400, H, 4.60; N, 25.27. 1340, 1274, 1256, 1160, 950, 782, 698 cm1; 1H NMR (CDCl3) d 8.25 (dd, J¼1.54, 4.41 Hz, 1H), 7.80–7.96 (m, 4.3.11. 5-Ethoxy-2-ethyl-4-phenyl-2H-pyridazin-3(2H)- 2H), 7.42–7.28 (m, 3H), 7.12–7.02 (m, 2H), 3.89 (q, one. Mp 88–89  C; IR (potassium bromide) n 3042, 2966, J¼7.2 Hz, 2H), 1.29 (t, J¼7.2 Hz, 3H) ppm; 13C NMR 1632, 1444, 1400, 1340, 1258, 1160, 950 cm1; 1H NMR (CDCl3) d 152.98, 147.92, 141.20, 137.96, 129.46, 128.17, (CDCl3) d 7.88 (s, 1H), 7.49–7.42 (m, 5H), 4.26 (q, 127.84, 122.90, 119.71, 64.10, 14.62 ppm. Elemental analy- J¼7.18 Hz, 2H), 3.86 (q, J¼7.11 Hz, 2H), 1.39 (t, sis calcd for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: J¼7.17 Hz, 3H), 1.28 (t, J¼7.13 Hz, 3H) ppm; 13C NMR C, 78.40; H, 6.61; N, 7.09. (CDCl3) d 160.71, 154.72, 130.42, 130.38, 128.25, 127.78, 127.63, 121.38, 57.15, 47.36, 13.59, 13.54 ppm. Elemental 4.3.18. 4-Methyl-3-nitrobiphenyl. Mp 61–62  C, IR analysis calcd for C14H16N2O2: C, 68.83; H, 6.60; N, (potassium bromide) n 3052, 2960, 1522, 1496, 1434, 880, 11.47. Found: C, 68.88; H, 6.67; N, 11.51. 742, 686 cm1; 1H NMR (CDCl3) d 8.12 (d, J¼1.93 Hz, 1H), 7.64 (dd, J¼1.95, 7.95 Hz, 1H), 7.54–7.50 (m, 2H), 4.3.12. Biphenyl-4-yl-methylamine. Mp 67–69  C; IR (po- 7.44–7.31 (m, 4H), 2.57 (s, 3H) ppm; 13C NMR (CDCl3) tassium bromide) n 3402, 3042, 2874, 2800, 1600, 1490, d 149.63, 140.27, 138.46, 133.24, 132.20, 131.25, 129.11, 822, 756 cm1; 1H NMR (CDCl3) d 7.55–7.51 (m, 2H), 128.27, 126.88, 122.87, 20.07 ppm. Elemental analysis 7.46–7.42 (m, 2H), 7.39–7.34 (m, 2H), 7.26–7.20 (m, 1H), calcd for C13H11NO2: C, 73.23; H, 5.20; N, 6.57. Found: 6.67–6.62 (m, 2H), 3.67 (br s, NH), 2.83 (s, 3H) ppm; 13C C, 73.26; H, 5.24; N, 6.61. NMR (CDCl3) d 148.81, 141.39, 130.23, 128.69, 127.94, 126.34, 126.07, 112.75, 30.80 ppm. Elemental analysis 4.3.19. 2-Phenylthioxanthen-9-one. Mp 128–129  C; IR calcd for C13H13N: C, 85.21; H, 7.15; N, 7.64. Found: C, (potassium bromide) n 3036, 1642, 1594, 1442, 1324, 85.24; H, 7.19; N, 7.70. 1136, 750 cm1; 1H NMR (CDCl3) d 8.84 (d, J¼2.11 Hz, 1H), 8.62 (dd, J¼1.30, 8.10 Hz, 1H), 7.82 (dd, J¼2.14, 4.3.13. 4-Vinylbiphenyl. Mp 118–120  C (lit.51 mp 119– 8.37 Hz, 1H), 7.70–7.67 (m, 2H), 7.60–7.55 (m, 3H), 7.49– 121  C); IR (potassium bromide) n 3006, 2996, 1464, 7.43 (m, 3H), 7.40–7.35 (m, 1H) ppm; 13C NMR (CDCl3) 1382, 994, 842 cm1; 1H NMR (CDCl3) d 7.60–7.54 (m, d 179.89, 139.48, 139.29, 137.16, 136.06, 132.24, 130.95, 4H), 7.49–7.39 (m, 4H), 7.34–7.29 (m, 1H), 6.75 (dd, 129.94, 129.47, 129.23, 128.99, 127.87, 127.80, 127.06, J¼10.88, 17.59 Hz, 1H), 5.75 (s, J¼17.59 Hz, 1H), 5.25 126.52, 126.31, 126.04 ppm. Elemental analysis calcd for (d, J¼10.88 Hz, 1H) ppm; 13C NMR (CDCl3) d 140.79, C19H12OS: C, 79.14; H, 4.19. Found: C, 79.18; H, 4.23. 140.64, 136.67, 136.47, 128.80, 127.33, 127.25, 126.99, 126.68, 113.89 ppm. Elemental analysis calcd for C14H12: 4.3.20. 2-Phenylpyrazine. Mp 74–75  C; IR (potassium C, 93.29; H, 6.71. Found: C, 93.32; H, 6.74. bromide) n 3050, 1474, 1447, 1409, 1082, 1010, 772, 744, 692 cm1; 1H NMR (CDCl3) d 9.00 (d, J¼1.54 Hz, 1H), 4.3.14. 4-Benzenesulfonylbiphenyl. Mp 148–149  C; IR 8.60 (dd, J¼1.61, 2.49 Hz, 1H), 8.47 (d, J¼2.51 Hz, 1H), (potassium bromide) n 3072, 1320, 1160, 1116 cm1; 1H 8.02–7.98 (m, 2H), 7.52–7.44 (m, 3H) ppm; 13C NMR NMR (CDCl3) d 8.01–7.96 (m, 4H), 7.69–7.66 (m, 2H), (CDCl3) d 152.84, 144.15, 142.81, 142.14, 136.28, 129.90, 7.58–7.35 (m, 8H) ppm; 13C NMR (CDCl3) d 146.18, 129.01, 126.92 ppm. Elemental analysis calcd for C10H8N2: 141.81, 140.20, 139.16, 133.19, 129.33, 129.06, 128.60, C, 76.90; H, 5.16; N, 17.94. Found: C, 76.98; H, 5.21; N, 18.01.  S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 1351 4.3.21. 3-(4-Methoxyphenoxy)-6-phenylpyridazine. Mp References and notes 171–172  C; IR (potassium bromide) n 3082, 2992, 1520, 1442, 1306, 1254, 1214, 1042, 850 cm1; 1H NMR 1. Handbook of Organopalladium Chemistry for Organic (CDCl3) d 8.03–7.98 (m, 2H), 7.85 (d, J¼9.21 Hz, 1H), Synthesis; Negishi, E.-I., Ed.; Wiley Interscience: New York, 7.51–7.44 (m, 3H), 7.20–7.08 (m, 3H), 6.97–6.92 (m, 2H), NY, 2002. 3.82 (s, 3H); 13C NMR (CDCl3) d 165.38, 157.04, 155.98, 2. Heck, R. F. Palladium Reagents in Organic Synthesis; 146.97, 135.98, 129.58, 128.93, 127.45, 126.62, 122.22, Academic: New York, NY, 1985. 117.35, 114.90, 55.68 ppm. Elemental analysis calcd for 3. Principles and Applications of Organotransition Metal C18H16N2O: C, 78.24; H, 5.84; N, 10.14. Found: C, 78.28; Chemistry; Collman, J. P., Hegedus, L. S., Norton, J. R., H, 5.90; N, 10.18. Finke, R. G., Eds.; University Science: Mill Valley, CA, 1987. 4. Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., 4.3.22. 2-Phenylquinoline. Mp 83–84  C (lit.53 mp 84– Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998. 85  C); IR (potassium bromide) n 3062, 3032, 1604, 5. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. 1550 cm1; 1H NMR (CDCl3) d 8.20–8.14 (m, 4H), 7.86– 6. Suzuki, A. Metal-Catalyzed Cross-Coupling Reagents; 7.78 (m, 2H), 7.73–7.68 (m, 1H), 7.54–7.42 (m, 4H) ppm; Diederichc, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 13 C NMR (CDCl3) d 157.41, 148.33, 139.72, 136.78, Germany, 1998, Chapter 2. 129.75, 129.67, 129.33, 128.85, 127.61, 127.47, 127.22, 7. Suzuki, A. J. Organomet. Chem. 1999, 576, 147. 126.29, 119.03 ppm. Elemental analysis calcd for 8. Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew. Chem., C15H11N: C, 87.77; H, 5.40; N, 6.82. Found: C, 87.80; H, Int. Ed. 2001, 40, 4544. 5.44; N, 6.86. 9. Miyaura, N. Top. Curr. Chem. 2002, 219, 11. 10. Hassan, J.; Sevignon, M.; Gozzi, C.; Shulz, E.; Lemaire, M. 4.3.23. 2-Phenylthiophene. Mp 34–36  C (lit.54 mp 34– Chem. Rev. 2002, 102, 1359. 36  C); IR (potassium bromide) n 3065, 3014, 1596, 1523, 11. Kotha, S.; Lahin, K.; Kashinath, D. Tetrahedron 2002, 58, 9633. 1486 cm1; 1H NMR (CDCl3) d 7.63–7.57 (m, 3H), 7.46– 12. Suzuki, A. Morden Arene Chemistry; Astruc, D., Ed.; Wiley- 7.26 (m, 5H) ppm; 13C NMR (CDCl3) d 141.27, 128.86, VCH: Weinheim, 2002; pp 53–106. 128.73, 127.44, 127.23, 127.16, 125.97, 124.77 ppm. Ele- 13. Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419. mental analysis calcd for C10H8S: C, 74.96; H, 5.03. Found: 14. Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed. C, 74.99; H, 5.09. 2000, 39, 4153. 15. Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H.-U. Angew. 4.3.24. 4-(Pyridine-4-yl)benzonitrile. Mp 77–78  C (lit.55 Chem., Int. Ed. 2002, 41, 3668. mp 75–76  C); IR (potassium bromide) n 3036, 2226, 16. Stambuli, J. P.; Kuwano, R.; Hartwig, J. F. Angew. Chem., Int. 1598, 1398 cm1; 1H NMR (CDCl3) d 8.73 (d, J¼4.85 Hz, Ed. 2002, 41, 4746. 2H), 7.73–7.81 (m, 4H), 7.51 (d, J¼5.93 Hz, 2H) ppm; 13C 17. Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org. NMR (CDCl3) d 150.60, 146.36, 142.62, 132.91, 127.77, Chem. 2002, 67, 5553. 121.62, 118.38, 112.83 ppm. Elemental analysis calcd for 18. Li, G. Y. J. Org. Chem. 2002, 67, 3643. C12H8N2: C, 79.98; H, 4.47; N, 15.55. Found: C, 80.01; H, 19. Hu, Q.; Lu, Y.; Tang, Z.; Yu, H. J. Am. Chem. Soc. 2003, 125, 4.50; N, 15.61. 2856. 20. Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. 4.3.25. 40 -(Dimethylamino)biphenyl-4-carbonitrile. Mp Angew. Chem., Int. Ed. 2003, 42, 3690. 218–220  C (lit.56 mp 222–223  C); IR (potassium bromide) 21. Jensen, J. F.; Johannsen, M. Org. Lett. 2003, 5, 3025. n 3048, 2910, 2226, 1593, 1529, 1492, 1446, 1360, 22. Roca, F. X.; Richards, C. J. J. Org. Chem. 2003, 68, 2592. 812 cm1; 1H NMR (CDCl3) d 7.63 (m, 4H), 7.51 (d, 23. Ozdemir, I.; Alici, B.; Gurbuz, N.; Cetinkaya, E.; Cetinkaya, B. J¼8.83 Hz, 2H), 6.79 (d, J¼8.85 Hz, 2H), 3.02 (s, J. Mol. Catal. A 2004, 37. 6H) ppm; 13C NMR (CDCl3) d 150.77, 145.59, 132.51, 24. Tewari, A.; Hein, M.; Zapf, A.; Beller, M. Synthesis 2004, 925. 127.88, 126.37, 126.32, 119.43, 112.54, 108.99, 25. an der Heiden, M.; Plenio, H. Chem.—Eur. J. 2004, 10, 1789. 40.33 ppm. Elemental analysis calcd for C15H14N2: C, 26. Colacot, T. L.; Shea, H. A. Org. Lett. 2004, 6, 3731. 81.05; H, 6.35; N, 12.60. Found: C, 81.01; H, 6.32; N, 12.59. 27. Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams, V. A.; Granados, P.; Singer, R. D. J. Org. Chem. 2005, 70, 161. 4.3.26. 40 -Formylbiphenyl-4-carbonitrile.17 Mp 151– 28. Zapf, A.; Beller, M. Chem. Commun. 2005, 431. 152  C (lit.57 mp 150–150.5  C); IR (potassium bromide) n 29. Lemo, J.; Heuze, K.; Astuc, D. Org. Lett. 2005, 7, 2253. 3043, 2226, 1702, 1598, 1394, 1261, 1095, 1022, 30. For a review on Pd-catalyzed couplings of aryl chlorides, see: 812 cm1; 1H NMR (CDCl3) d 10.09 (s, 1H), 7.71–8.02 Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176. (m, 8H) ppm; 13C NMR (CDCl3) d 191.60, 144.92, 31. Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 144.16, 136.15, 132.80, 130.43, 128.05, 127.93, 366 and references therein. 112.18 ppm. Elemental analysis calcd for C14H9NO: 32. Miura, M. Angew. Chem., Int. Ed. 2004, 43, 2201. C, 81.14; H, 4.38; N, 6.76. Found: C, 81.13; H, 4.40; N, 6.79. 33. Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998, 39, 617. 34. Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, Acknowledgements K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, 5575. 35. Reddy, N. P.; Tanaka, M. Tetrahedron Lett. 1997, 38, 4807. This study was financially supported by Pusan National 36. Wolfe, J. P.; Tomori, J.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. University in Program Post-Doc 2006. J. Org. Chem. 2000, 65, 1158. 1352 S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352 37. Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Kalpars, A.; 48. Handbook of Organopalladium Chemistry for Organic Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653. 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