HETEROCYCLES

Paper | Regular issue | Vol. 81, No. 8, 2010, pp. 1881-1889
Received, 23rd May, 2010, Accepted, 22nd June, 2010, Published online, 23rd June, 2010.
DOI: 10.3987/COM-10-11982

■ Effect of Oxygen Substituent in the Aniline Part of Benzanilide on the Regioselectivity in Direct Arylation Using Palladium-Phosphine Reagents

Takashi Harayama,* Mariko Asai, Taeko Miyagoe, Hitoshi Abe, Yasuo Takeuchi, Ayako Yamaguchi, and Shinya Fujii

Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa 769-2193, Japan

Abstract

This study investigated the effect of oxygen substituents at the 3’-position in the aniline part of 2-iodobenzanilides on the coupling position in its Pd-assisted direct arylation. Benzanilide with methylenedioxy and acetoxy groups yielded the ortho-product formed predominantly by connection to a more hindered carbon. The mechanism is discussed from the perspectives of both steric and coordinated effects.

Direct arylation1a (aryl-aryl coupling reaction) of a nonactivated aryl C-H bond with an activated arene by palladium-phosphine reagent has been used to synthesize many condensed aromatic compounds.1 Recently, we reported that an intramolecular direct arylation of 2-halo-N-arylbenzamides using palladium reagents was a convenient method for synthesizing polycyclic aromatic lactams, some of which can be transformed into aromatic alkaloids.2 Moreover, we successfully synthesized benzonaphthazepine, a new skeletal compound, and pyrrolophenanthridine (Amaryllidaceae) alkaloids, utilizing a Pd-assisted biaryl coupling reaction with regioselective C–H activation via the intramolecular coordination of an amine to Pd.3 Subsequently, we applied the direct arylation using Pd to the synthesis of quinazoline alkaloids4,5 and benzpyranones. 4,5
Examining the synthesis of trisphaeridine, we found that the Pd-mediated coupling reaction of N-(2-iodophenyl)benzamide possessing a methylenedioxy group in the benzoyl part produced the ortho-product, which was formed by connection to a more hindered carbon and the para-product in a 4 to 1 ratio.6 Subsequently, we investigated the effect of several oxygen substituents in the benzoyl part of N-(2-iodophenyl)benzamide (A) on the coupling position in its Pd-assisted biaryl coupling reaction. We reported that benzamide with methylenedioxy and acyloxy groups yielded the ortho-product (B) formed predominantly by connection to a more hindered carbon and benzamide with methoxy and phenol groups gave the ortho-product (B) and the para-product (C) in almost equal amounts.7
In order to investigate the generality of oxygen-substituent effect on coupling position, we examined biaryl coupling reaction of 2-iodo-N-methylbenzanilides (1) possessing oxygen-substituents in the aniline part.

The results of the coupling reactions using methods A [Pd(OAc)2 (10 mol%), PPh3 (20 mol%), and K2CO3 (200 mol%)], B8 [Pd(OAc)2 (100 mol%), DPPP (100 mol%), n-Bu3P (100 mol%), and Ag2CO3 (200 mol%)], and C [Pd(OAc)2 (10 mol%), (o-tol)3P (20 mol%), and K2CO3 (200 mol%)] in DMF under reflux are summarized in Table 1.
First, the direct arylations of 1 using Method A were examined. The compound (1a) possessing a methylenedioxy group gave the ortho-product (2a) as the major product, and the acetate (1c) gave the ortho-product (2d) selectively.9 Interestingly, these products are formed by connection to a more hindered carbon. By contrast, the reaction of benzamides (1b and d) possessing methoxy and hydroxyl group under the same reaction conditions gave the corresponding coupling products (2 and 3) in a ratio of 1.1~1.4 to 1, showing nearly equal selectivity. (See Table 1)
The regioselectivity of the coupling reaction involving two possible positions, C2 (ortho) and C6 (para), can be discussed based on steric and electronic effects. The difference in the regioselectivity of methoxy and methylenedioxy groups reflects the steric bulkiness of the methoxy group10 and the fact that the lone pair of electrons in the methylenedioxy oxygen atom is more electronegative than that in the methoxy oxygen atom because of reduced resonance of the π-electron on the benzene ring.11 Therefore, the lone pair of electrons in the methylenedioxy oxygen atom would coordinate to the PdII more tightly to produce the ortho-product predominantly.

All of the reactions using our new method (Method B)8 yielded the ortho-product (2) as the major product; which was more sterically hindered than the para-product (3), in comparison with Method A. This indicates that a bidentate ligand (DPPP) is sterically smaller than two monodentate ligands (PPh3) and suggests that the bulkiness of the ligand affects the regioselectivity. Therefore, reactions were carried out using Method C with (o-tol)3P, which has a larger cone angle and is bulkier than PPh3 as the ligand.12 Table 1 summarizes the results using Method C. The general decrease in ortho-products (2) from the coupling reaction at the sterically hindered position indicates that ligand bulkiness influences regioselectivity.13 These results are very similar to those of direct arylation of benzamides (A) possessing oxygen substituents in the benzoyl part.7,14
Recently, several mechanistic pathways for direct arylation (aryl-aryl coupling reaction) have been proposed.1a, 15 We presented that the formation of aryl-aryl bond would proceed via a σ-bond metathesis (C-H activation). 16 According to our proposal, the ortho-product (2) would be predominantly formed via the intermediate (D) and (E), respectively.

In conclusion, the ratio of 2 to 3 was influenced by the coordinating ability of substituent(s) to the PdII complex and by the steric relationship between the substituent(s) and the phosphine ligand. More detailed investigations of direct arylation mechanism are now in progress.

EXPERIMENTAL
Melting points were measured on a micro-melting point hot-stage apparatus (Yanagimoto) and are uncorrected. IR spectra were recorded on a JASCO FT/IR 350 spectrophotometer and 1H-NMR spectra in deuteriochloroform on Varian Mercury 300 or VXR-500 spectrometers. NMR spectral data are reported in parts per million downfield from tetramethylsilane as the internal standard (δ 0.0), and the coupling constants are given in Hertz. MS spectra were obtained on a VG-70SE. Analytical HPLC was performed with a Shimadzu SPD-6A on a silica gel column (Chemcosorb 5Si-U). Column chromatography was carried out on a Merck silica gel (230–400 mesh). All the extracts were washed with brine, dried over anhydrous MgSO4, and filtered; the filtrate was concentrated to dryness under reduced pressure.

N-(1,3-Benzodioxol-yl)-2-iodo-N-methylbenzanilide (1a)
A mixture of 3,4-methylenedioxyaniline(2.06 g, 15.0 mmol), 2-iodobenzoic acid (4.84 g, 19.5 mmol), N-ethyl-N’-(3-dimethylaminopropyl)carbodiimide (EDC) (4.95 g, 25.8 mmol), and 4-dimethylaminopyridine (0.40 g, 3.3 mmol) in dry CH2Cl2 (12 mL) was stirred at rt for 30 min under an argone atmosphere. The reaction mixture was poured into water and the aqueous layer was extracted with AcOEt.. The organic layer was washed with 10% HCl, 5% aqueous NaHCO3 solution, and brine. The residue was recrystalized from AcOEt to give N-(1,3-benzodioxol-5-yl)-2-iodobenzanilide (3.25 g, 59 %) as colorless needles, mp 204–206 ˚C. IR (KBr) cm-1: 3050, 1650, 1450. Anal. Calcd for C14H10NO3I: C, 45.80; H, 2.75; N, 3.82. Found: C, 45.82; H, 2.97; N, 3.84.
Methyl iodide (0.30 mL, 4.5 mmol) was added to a suspension of N-(1,3-benzodioxol-5-yl)-2- iodobenzanilide (1.10 g, 3.0 mmol) and NaH (60%, 0.46 g, 9.0 mmol) in dry DMF (32 mL). After stirring at rt for 15 min, the excess NaH was decomposed with ice water, and the aqueous layer was extracted with AcOEt. The residue in AcOEt was subjected to column chromatography on a silica gel. Elution with hexane:AcOEt (2:1) gave 1a (1.10 g, 96.7%) as colorless prisms (from hexane:AcOEt), mp 71-74 ˚C. IR (KBr) cm-1: 1650. 1H-NMR (500 MHz) : 3.44 (3H, s), 5.90 (2H, s), 6.57 (1H, d, J = 8.5 Hz), 6.66 (1H, dd, J = 8.5, 2.0 Hz), 6.72 (1H, d, J = 2.0 Hz), 6.88 (1H, ddd, J = 7.5, 7.5, 1.5 Hz), 7.05 (1H, dd, J = 7.5, 1.5 Hz), 7.15 (1H, dd, J = 7.5, 7.5 Hz), 7.68 (1H, br d, J =8.0 Hz). Anal. Calcd for C15H12NO3I: C, 47.27; H, 3.17; N, 3.67. Found: C, 47.31; H, 3.26; N, 3.60.
2-Iodo-3’-methoxy-N-methylbenzanilide (1b)
Methyl iodide (0.55 mL, 8.16 mmol) was added to a suspension of 2-iodo-3-methoxybenzanilide17 (2.0 g, 5.44 mmol) and NaH (60%, 0.65 g, 16.32 mmol) in dry DMF (30 mL). After stirring for 15 min at rt, the excess NaH was decomposed with ice water, and the aqueous layer was extracted with AcOEt. The residue in AcOEt was subjected to column chromatography on a silica gel. Elution with hexane:AcOEt (1:1) gave 1b (1.10 g, 96.7%) as colorless oil. IR (KBr) cm-1: 1640. 1H-NMR (500 MHz) : 3.51 (3H, s), 3.69 (3H, s), 6.65 (1H, dd, J = 8.5, 2 Hz), 6.73 (1H, dd, J = 2.0, 2.0 Hz), 6.76 (1H, br. d, J = 8.0 Hz), 6.87 (1H, br t, J = 7.5 Hz), 7.04 (1H, br d, J = 7.5 Hz), 7.09 (1H, br t, J = 8.5 Hz), 7.13 (1H, br t, J = 7.5 Hz),, 7.68 (1H, d, J = 7.5 Hz). High resolution MS (FAB) m/z: Calcd for C15H14NO3I [M+1]+: 368.0148. Found: 368.0102.
3-(2-Iodo-N-methylbenzamido)phenyl acetate (1c)
A mixture of m-aminophenol (3.27 g, 30.0 mmol), 2-iodobenzoic acid (9.67 g, 39.0 mmol), EDC (9.78 g, 51.0 mmol), and 4-dimethylaminopyridine (0.73 g, 6.0 mmol) in dry CH2Cl2 (300 mL) was stirred at rt for 30 min under an argone atmosphere. The reaction mixture was poured into water and the aqueous layer was extracted with AcOEt. The extracts were washed with 10% HCl, 5% aqueous NaHCO3 solution, and brine. A solution of the residue in EtOH (50 mL) and 5% aqueous NaOH solution (50 mL) was stirred at rt for 30 min and was acidified with 10% HCl solution. The mixture was concentrated under reduced pressure and was extracted with AcOEt. The organic layer was washed with 5% aqueous NaHCO3 solution and brine. The residue was recrystalized from AcOEt to give 2’-iodo-3-hydroxybenzanilide (3.54 g, 34.8 %) as colorless prisms, mp 171–173 ˚C. IR (KBr) cm-1: 3200, 1650, 1440. Anal. Calcd for C13H10NO2I: C, 46.04; H, 2.97; N, 4.13. Found: C, 45.92; H, 2.97; N, 4.08.
A solution of 2’-iodo-3-hydroxybenzanilide (890 mg, 2.62 mmol) in acetic anhydride (0.58 mL), 5.24 mmol) and pyridine (5 mL) was stirred for 45 min at rt. The reaction mixture was made acidic with 10% HCl solution and the aqueous layer was extracted with AcOEt. The organic layer was washed with 5% aqueous NaHCO3 solution and brine. The residue was recrystallized from AcOEt-hexane to afford 3-(2-iodobenzamido)phenyl acetate (909 mg, 91%), as colorless prisms, mp 115–118 ˚C. IR (KBr) cm-1: 3250, 1760, 1660. Anal. Calcd for C15H12NO3I: C, 47.27; H, 3.17; N, 3.67. Found: C, 47.42; H, 3.26; N, 3.62.
Methyl iodide (0.45 mL, 6.75 mmol) was added to a suspension of 3-(2-iodobenzamido)phenyl acetate (1.72 g, 4.5 mmol) and NaH (60%, 0.20 g, 5.0 mmol) in dry DMF (45 mL). After stirring for 15 min under ice cooling, the excess NaH was decomposed with ice water, and the quenched mixture was made acidic with 10% HCl solution, and then extracted with AcOEt. The residue in AcOEt was subjected to column chromatography on a silica gel. Elution with CHCl3:hexane:AcOEt (5:3:1) gave 1c (1.63 g, 91.7%) as oil. IR (KBr) cm-1: 1760, 1650. 1H-NMR (500 MHz) : 2.26 (3H, s), 3.51 (3H, s), 6.87 (2H, m), 6.97 (1H, br. s), 7.01 (1H, br d, J = 7.0 Hz), 7.05 (1H, br d, J = 6.0 Hz), 7.15 (2H, m), 7.67 (1H, br d, J = 7.5 Hz). High resolution MS (FAB) m/z : Calcd for C16H14NO3I [M+1]+: 396.0096. Found: 396.0095.
3-(2’-Iodo-N-methylbenzamido)phenol (1d)
Aqueous 5% NaHCO3 solution (18 mL) was added to a solution of 1c (1.0 g, 2.53mmol) in MeOH (36 mL) under ice cooling and the mixture was stirred at rt over night. The reaction mixture was made acidic with 10% HCl solution and extracted with AcOEt. The residue was recrystallized from AcOEt-hexane to afford 1d (0.89 g, 89.3 %) as colorless prisms, mp 171-173 ˚C. IR (KBr) cm-1: 3200, 1626, 1591. 1H-NMR (300 MHz, d6-DMSO): 3.29 (3H, s), 6.60 (1H, d, J = 7.9 Hz), 6.73 (1H, br d, J = 8.0 Hz), 6.75 (1H, br s), 7.00 (1H, t, J = 7.2 Hz), 7.04 (1H, t, J = 7.9 Hz), 7.21 (1H, br d, J = 7.2 Hz), 7.28 (1H, t, J = 7.2 Hz), 7.75 (1H, d, J = 8.0 Hz), 9.19 (1H, s),. Anal. Calcd for C14H12NO2I: C, 47.61; H, 3.43; N, 3.97. Found: C, 47.53; H, 3.49; N, 3.88.
General Procedure for the Coupling Reaction of Benzanilides (1)
Coupling reaction was carried out under the reaction conditions indicated in Table 1. Then, the reaction mixture of 1a, 1b, and 1d was diluted with AcOEt, and the precipitates were removed by filtration. The filtrate was washed with brine.
Biaryl Coupling Reaction of N-(1,3-benzodioxol-yl)-2-iodo-N-methylbenzamide (1a)
The residue was dissolved in CHCl3 and was subjected to column chromatography on silica gel. Elution with CHCl3:hexane:AcOEt (5:3:1) gave 5-methyl-[1,3]dioxolo[4,5-a]phenanthridin-6(5H)-one (2a) and successive elution with the same solvent gave 5-methyl-[1,3]dioxolo[4,5-b]phenanthridin-6(5H)-one (3a).
5-Methyl-[1,3]dioxolo[4,5-a]phenanthridin-6(5H)-one (2a): colorless needles (from AcOEt), mp 200-202 ˚C. IR (KBr) cm-1: 1650. 1H-NMR (500 MHz, CDCl3) δ: 3.77 (3H, s), 6.21 (2H, s), 6.88(1H, d, J = 8.5 Hz), 7.04 (1H, d, J = 8.5 Hz), 7.59 (1H, ddd, J = 8.0, 7.5, 1.0 Hz), 7.74 (1H, ddd, J = 8.0, 7.5, 1.0 Hz), 8.55 (1H, dd, J = 8.0, 1.5 Hz), 8.68 (1H, dd, J = 8.5, 1.0 Hz). Anal. Calcd for C15H11NO3: C, 71.14; H, 4.38; N,5.53. Found: C, 71.29; H, 4.52; N, 5.50.
5-Methyl-[1,3]dioxolo[4,5-b]phenanthridin-6(5H)-one (3a): colorless needles (from AcOEt), mp 240-243 ˚C. IR (KBr) cm-1: 1650. 1H-NMR (500 MHz, CDCl3) δ: 3.78 (3H, s), 6.08 (2H, s), 6.95 (1H, s), 7.52 (1H, dd, J = 7.5, 7.5 Hz), 7.67 (1H, s), 7.72 (1H, ddd, J = 7.5, 7.5, 1.5 Hz), 8.06 (1H, d, J = 8.0 Hz), 8.52 (1H, dd, J = 8.0, 1.5 Hz). Anal. Calcd for C15H11NO3: C, 71.14; H, 4.38; N,5.53. Found: C, 71.12; H, 4.51; N, 5.68.
Biaryl Coupling Reaction of 2-Iodo-3’-methoxy-N-methylbenzamide (1b)
The residue was dissolved in CHCl3 and subjected to column chromatography on silica gel. Elution with hexane:i-Pr2O (2:1) gave 5-methyl-1-methoxyphenanthridin-6(5H)-one (2b) and successive elution with the same solvent gave 5-methyl-3-methoxyphenanthridin-6(5H)-one (3b).
5-Methyl-1-methoxyphenanthridin-6(5H)-one (2b): colorless needles (from AcOEt), mp 156.5-158 ˚C. IR (KBr) cm-1: 1645. 1H-NMR (500 MHz, CDCl3) δ: 3.81 (3H, s), 4.07 (3H, s), 6.90 (1H, d, J = 8.0 Hz), 7.09 (1H, d, J = 8.0 Hz), 7.47 (1H, dd, J = 8.0, 8.0 Hz), 7.56 (1H, ddd, J = 7.5, 7.5, 1.0 Hz), 7.72 (1H, ddd, J = 8.5, 7.5, 1.5 Hz), 8.60 (1H, ddd, J = 8.0, 1.5, 0.5 Hz), 9.22 (1H, dd, J = 8.5, 1.0 Hz). Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N,5.85. Found: C, 75.21; H, 5.65; N, 5.94.
5-Methyl-3-methoxyphenanthridin-6(5H)-one (3b): colorless needles (from CHCl3-Et2O), mp 91.5-93 ˚C. IR (KBr) cm-1: 1650. 1H-NMR (500 MHz, CDCl3) δ: 3.77 (3H, s), 3.93 (3H, s), 6.86 (1H, d, J = 2.5 Hz), 6.89 (1H, dd, J = 8.5, 2.5 Hz), 7.50 (1H, ddd, J = 8.0, 7.0, 1.0 Hz), 7.70 (1H, ddd, J = 8.0, 7.0, 1.3 Hz), 8.13 (1H, dd, J = 8.0, 1.0 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.94 (1H, ddd, J = 8.0, 1.5, 1.0 Hz). Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N,5.85. Found: C, 75.22; H, 5.49; N, 5.82.
Biaryl Coupling Reaction of 3-(2-iodo-N-methylbenzamido)phenyl acetate (1c)
Water (1 mL) was added to the reaction mixture and was stirred for 15 min under reflux. The reaction mixture was acidified with 10% HCl and extracted with AcOEt. The residue was dissolved in CHCl3–EtOH and subjected to column chromatography on silica gel. Elution with CHCl3:hexane:AcOEt (5:3:1) gave 1-hydroxy-5-methylphenanthridin-6(5H)-one (2d) and successive elution with the same solvent gave 3-hydroxy-5-methylyphenanthridin-6(5H)-one (3d).
1-Hydroxy-5-methylphenanthridin-6(5H)-one (2d): colorless needles (from EtOH), mp 285-289 ˚C. IR (KBr) cm-1: 3150, 1605. 1H-NMR (500 MHz, d6-acetone) δ: 3.76 (3H, s), 6.93 (1H, d, J = 8.0 Hz), 7.10 (1H, d, J = 8.0 Hz), 7.39 (1H, dd, J = 8.0, 8.0 Hz), 7.56 (1H, dd, J = 8.0, 8.0 Hz), 7.72 (1H, ddd, J = 8.5, 7.5, 1.5 Hz), 8.50 (1H, dd, J = 8.0, 2.0 Hz), 9.43 (1H, d, J = 8.0 Hz). Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N,6.22. Found: C, 74.58; H, 4.78; N, 6.19.
3-Hydroxy-5-methylyphenanthridin-6(5H)-one (3d): colorless prisms (from EtOH), mp 218-221 ˚C. IR (KBr) cm-1: 3150, 1610. 1H-NMR (500 MHz, d6-acetone) δ: 3.71 (3H, s), 6.87 (1H, dd, J = 8.0, 2.5 Hz), 6.97 (1H, d, J = 2.5 Hz), 7.50 (1H, ddd, J = 8.0, 8.0, 1.5 Hz), 7.75 (1H, ddd, J = 8.0, 8.0, 1.5 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.31 (1H, d, J = 8.0 Hz), 8.38 (1H, dd, J = 8.0, 1.5 Hz). Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N, 6.22. Found: C, 74.55; H, 4.99; N, 6.26.
Biaryl Coupling Reaction of 3-(2’-iodo-N-methylbenzamido)phenol (1d)
The reaction mixture was acidified with 10% HCl and extracted with AcOEt. The residue was dissolved in CHCl3–EtOH and subjected to column chromatography on silica gel. Elution with CHCl3:hexane:AcOEt (5:3:1) gave gave 1-hydroxy-5-methylphenanthridin-6(5H)-one (2d) and successive elution with the same solvent gave 3-hydroxy-5-methylyphenanthridin-6(5H)-one (3d).

References

1. a) D. Arberico, M. E. Scott, and M. Lautens, Chem. Rev., 2007, 107, 174; CrossRef b) G. Zeni and R. C. Larock, Chem. Rev., 2006, 106, 4644; CrossRef c) J.-P. Corbet and G. Mignani, Chem. Rev., 2006, 106, 2651; CrossRef d) J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, and M. Lemaire, Chem. Rev., 2002, 102, 1359; CrossRef e) J. J. Li and G. W. Gribble, Palladium in Heteocyclic Chemistry, Pergamon, Oxford, 2000.
2. T. Harayama, Heterocycles, 2005, 65, 697. CrossRef
3. T. Harayama, Recent Res. Devel. Organic Chem., 2005, 9, 15.
4. H. Abe and T. Harayama, Heterocycles, 2008, 75, 1305. CrossRef
5. T. Harayama, Yakugaku Zasshi, 2006, 126, 543. CrossRef
6. T. Harayama, H. Akamatsu, K. Okamura, T. Miyagoe, T. Akiyama, H. Abe, and Y. Takeuchi, J. Chem. Soc., Perkin Trans. 1, 2001, 523. CrossRef
7. T. Harayama, Y. Kawata, C. Nagura, T. Sato, T. Miyagoe, H. Abe, and Y. Takeuchi, Tetrahedron Lett., 2005, 46, 6091. CrossRef
8. (a) T. Harayama, T. Akiyama, Y. Nakano, H. Nishioka, H. Abe, and Y. Takeuchi, Chem. Pharm. Bull., 2002, 50, 519; CrossRef (b) T. Harayama, T. Akiyama, Y. Nakano, K. Shibaike, H. Akamatsu, A. Hori, H. Abe, and Y. Takeuchi, Synthesis, 2002, 237. CrossRef
9. The ratio was determined by the NMR method after alkaline hydrolysis because the coupling products always contained some of the hydrolyzed products (2d and 3d).
10. (a) J. M. Vila, A. Suarez, M. T. Pereira, E. Gayoso, and M. Gayoso, Polyhedron, 1987, 6, 1003; CrossRef (b) B. Teijido, A. Fernández, M. López-Torres, S. Castro-Juiz, A. Suárez, J. M. Ortigueira, J. M. Vila, and J. J. Fernández, J. Organomet. Chem., 2000, 598, 71. CrossRef
11. T. F. Buckley III and H. Rapoport, J. Am. Chem. Soc., 1980, 102, 3056. CrossRef
12. C. A. Tolmann, Chem. Rev., 1977, 77, 313. CrossRef
13. Reactions using bulky biphenyl phosphine ligand gave para-products in ratios exceeding 20 to 1. L.-C. Campeau, M. Parisien, M. Leblanc, and K. Fagnou, J. Am. Chem. Soc., 2004, 126, 9186. CrossRef
14. The ratio of coupling products of phenol (Id) might reflect both the steric bulkiness and electronic effects of phenoxide.
15. a) E. D. Hennessy and S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 12084; CrossRef b) S. I. Gorelsky, D. Lapointe, and K. Fagnou, J. Am. Chem. Soc., 2008, 130, 10848; CrossRef c) S. Pascual, P. de Mendoza, A. A. C. Braga, F. Maseras, and A. M. Echavarren, Tetrahedron, 2008, 64, 6021; CrossRef d) T. Watanabe, S. Oishi, N. Fujii, and H. Ohno, J. Org. Chem., 2009, 74, 4720. CrossRef
16. H. Nishioka, C. Nagura, H. Abe, Y. Takeuchi, and T. Harayama, Heterocycles, 2006, 70, 549. CrossRef
17. D. H. Hey, G. H. Jones, and M. J. Parkins, J. Chem. Soc., Perkin Trans. 1, 1972, 1150. CrossRef