Supporting Information

Supporting Information Wiley-VCH 2011 69451 Weinheim, Germany Assembly of Substituted 2-Alkylquinolines by a Sequential Palladium- Catalyzed C and CC Bond Formation Yoshio Matsubara,* Saori Hirakawa, Yoshihiro Yamaguchi, and Zen-ichi Yoshida* anie_201102076_sm_miscellaneous_information.pdf

Contents 1. General Information. 2. Typical Procedure for PdCl 2 -catalyzed Reaction. 3. Reactants. 4. Characterization of Products. 5. Reaction Profile by HPLC. 6. Formation of -Alkylaniline (Side Product). 7. Examination of Reaction Pathway. 7-1. HPLC of The Reaction mixture. 7-2. PdCl 2 -Catalyzed Reaction of Compounds 11a (cis and trans) Leading to 1a. 7-3. Proposed mechanism for the Formation of 2-Methylqunoline (1a). 8. Proposed Reaction Sequence for the Synthesis of 2-Ethyl-3-methylqunoline.

1. General Information. All reagents were of commercial quality from freshly opened containers or were purified before use. Melting points were obtained on a Yanaco hot-stage micro melting point apparatus and not collected. 1 H and 13 C MR spectra were recorded on the Varian Mercury 300 spectrometer in CDCl 3 (300 MHz for 1 H, 75 MHz for 13 C) at 270 and 68 MHz, respectively. High-resolution mass (HR-MS) and low-resolution mass (LR-MS) spectra were obtained on a JMS-700TKM spectrometer. Reversed-phase HPLC were run on a SHIMADZU LC-10A using prepacked column of GL Science Inc. InersiODS-2 with methanol-h 2 0 (8:2 or 7:3) as a solvent (flow rate, 1 ml/min.; detection 254 nm). GLC were run on a SHIMADZU GC-14B using glass packed column SE-30 (5 mm 1 m or 3 m) with He gas (TCD detection). Column chromatography was performed using silica gel (PSQ 100B, Fuji Silysia). 2. Typical Procedure for The Catalytic Reaction. Typical procedure for the palladium-catalyzed reaction for synthesis of 2-methylquinolines and 2-ethyl-3-methylqunolines is described at Experimental Section of the text. 3. Reactants Aniline (1a), p-toluidine (2b), m-toluidine (2c), o-toluidine (2d), 4-methoxyaniline (2e), 3-methoxyaniline (2f), 2-methoxyaniline (2g), 4-fluoroaniline (2h), 3-fluoroaniline (2i), 4-chloroaniline (2j), 3-chloroaniline (2k), 4-bromoaniline (2l), methyl 4-aminobenzoate (2m), 4-amino-,-dimethylbenzamide (2n), 1-(4-aminophenyl)ethanone (2o), (4-aminophenyl)(phenyl)methanone (2p), and 1-naphtylamine (7) are commercially available. 2,4,5-Trimethoxyaniline (3x) was synthesized by the literature methods. [1] [1] B. K. Chan, M. A. Ciufolini, J. Org. Chem. 2007, 72, 8489-8495. 4. Characterization of Products. 2-Methylquinolines (1) 2-Methylquinoline (1a), [2] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ): δ = 7.97 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.61 (dd, J = 8.0 Hz, J = 7.1 Hz, 1H), 7.41 (dd, J = 8.1 Hz, J = 7.6 Hz, 1H), 7.21 (d, J = 8.1 Hz, 1H), 2.68 (s, 3H); HRMS (EI) m/z 143.0743 calcd for C 10 H 9 143.0735.

2,6-Dimethylquinoline (1b), [2] mp 56-58 o C, 1 H-MR (300 MHz, CDCl 3 ): δ = 8.00 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.55 (s, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 2.76 (s, 3H), 2.52 (s, 3H); HRMS (EI) m/z 157.0201 calcd for C 11 H 11 157.0891. 2,7-Dimethylquinoline (1c), [3] mp 58-60 o C, 1 H-MR (300 MHz, CDCl 3 ): δ = 7.99 (d, J = 8.7 Hz, 1H), 7.80 (s, 1H), 7.65 (d, 3 J = 8.4 Hz, 1H), 7.31 (d, 3 J = 8.7 Hz, 1H), 7.21 (d, 3 J = 8.4 Hz, 1H), 2.72 (s, 3H), 2.54 (s, 3H); HRMS (EI) m/z 157.0889 calcd for C 11 H 11 157.0891. 2,8-Dimethylquinoline (1d), [2] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ): δ = 8.00 (d, J = 8.4 Hz, 1H), 7.60 (d, 3 J = 7.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.36 (dd, J = 7.8 Hz, J = 7.8 Hz, 1H), 7.27 (d, J =7.8 Hz, 1H), 2.80 (s, 3H), 2.76 (s, 3H); HRMS (EI) m/z 157.0899 calcd for C 11 H 11 157.0891. 6-Methoxy-2-methylquinoline (1e), [2] mp 66-67 o C, 1 H-MR (400 MHz, CDCl 3 ): δ = 7.94 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.8 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.04 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H); HRMS (EI) m/z 173.0857 calcd for C 11 H 11 O 173.0840. 7-Methoxy-2-methylquinoline (1f), [4] Viscous liquid, 1 H-MR (400 MHz, CDCl 3 ): δ = 7.96 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 9.2 Hz, 1H), 7.36 (s, 1H), 7.15 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 9.2 Hz, 1H), 3.94 (s, 3H), 2.72 (s, 3H); HRMS (EI) m/z 173.0817 calcd for C 11 H 11 O 173.0840. 8-Methoxy-2-methylquinoline (1g), [2] mp 123-124 o C, 1 H-MR (400 MHz, CDCl 3 ): δ = 8.02 (d, J = 8.4 Hz, 1H), 7.40 (dd, J = 8.0 Hz, J = 7.6 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 4.07 (s, 3H), 2.77 (s, 3H); HRMS (EI) m/z 173.0825 calcd for C 11 H 11 O 173.0840. 6-Fluoro-2-methylquinoline (1h), [5] mp 52-53 o C, 1 H-MR (400 MHz, CDCl 3 ): δ = 8.01 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.39 (s, 1H), 7.30 (d, J = 8.0 Hz, 1H), 2.74 (s, 3H); HRMS (EI) m/z 161.0673 calcd for C 10 H 8 F 161.0640. 7-Fluoro-2-methylquinoline (1i), [6] mp 45-46 o C, 1 H-MR (300 MHz, CDCl 3 ): δ = 8.01 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.64 (s, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 2.72 (s, 3H); HRMS (EI) m/z 161.0619 calcd for C 10 H 8 F 161.0640 6-Chloro-2-methylquinoline (1j), [7] mp 95-98 o C, 1 H-MR (400 MHz, CDCl 3 ): δ = 7.97 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 2.75 (s, 3H); HRMS (EI) m/z 177.0358 calcd for C 10 H 8 Cl 177.0345. 7-Chloro-2-methylquinoline (1k), [8] mp 75-77 o C, 1 H-MR (300 MHz, CDCl 3 ): δ = 8.01 (d, J = 8.7 Hz, 1H), 8.00 (s, 1H), 7.70 (d, J = 8.7 Hz, 1H), 7.43 (d, J = 8.7 Hz, 1H),

7.28 (d, J = 8.7 Hz, 1H), 2.74 (s, 3H); HRMS (EI) m/z 177.0338 calcd for C 10 H 8 Cl 177.0345. 6-Bromo-2-methylquinoline (1l), [9] mp 101-105 o C, 1 H-MR (300 MHz, CDCl 3 ): δ = 7.93 (d, J = 8.4 Hz, 1H), 7.90 (s, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 2.72 (s, 3H); HRMS (EI) m/z 220.9780 calcd for C 10 H 8 Br 220.9840. Methyl 2-methylquinoline-6-carboxylate (1m), [10] mp 103-105 o C, 1 H-MR (300 MHz, CDCl 3 ): δ = 8.54 (s, 1H), 8.30 (d, J = 8.7 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 3.99 (s, 3H), 2.78 (s, 3H) ; 13 C-MR (75 MHz, CDCl 3 ): δ = 166.72, 161.59, 149.71, 137.30, 130.67, 128.99, 128.84, 127.18, 125.56, 122.82, 52.34, 25.57 ; HRMS (EI) m/z 201.0835 calcd for C 12 H 11 O 2 201.0789.,-2-Trimethylquinoline-6-carboxamide (1n), mp 135-136 o C, 1 H-MR (400 MHz, CDCl 3 ): δ 8.06 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 9.6 Hz, 1H), 7.87 (s 1H), 7.71 (d, J = 9.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 3.16 (s, 3H), 3.03 (s, 3H), 2.75 (s, 3H); 13 C-MR (75 MHz, CDCl 3 ): δ 170.87, 160.11, 147.76, 136.34, 133.14, 128.63, 127.81, 126.46, 125.71, 122.60, 39.48, 35.28, 25.23; HRMS (EI) m/z 214.1100 calcd for C 13 H 14 2 O 214.1106. 6-Acetyl-2-methylquinoline (1o), [11] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ): δ 8.41 (d, J = 1.8 Hz, 1H), 8.23 (dd, J = 8.8 Hz, J = 1.8 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.07(d, J = 8.8 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 2.78 (s, 3H), 2.73 (s, 3H); HRMS (EI) m/z 185.0835 calcd for C 12 H 11 O 185.0841. 6-Benzo-2-methylquinoline (1p), Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ): δ 8.23-8.10 (m, 3H), 7.86 (d, J = 8.4 Hz, 1H), 7.75-7.48 (m, 5H), 7.37 (d, J = 8.4 Hz, 1H), 2.79 (s, 3H) ; 13 C-MR (75 MHz, CDCl 3 ): δ 196.38, 161.89, 149.77, 137.85, 137.60, 134.86, 132.79, 131.44, 130.28, 129.86, 129.22, 128.65, 128.28, 123.20, 25.86 ; HRMS (EI) m/z 247.0939 calcd for C 17 H 13 O 247.0997. 5,6,8-Trimethoxy-2-methylquinoline (4), mp 107-108 o C, 1 H-MR (300 MHz, CDCl 3 ): δ 8.30 (d, J = 9.0 Hz, 1H), 7.31 (d, J = 9.0 Hz, 1H), 6.84 (s, 1H), 4.07 (s, 3H), 4.02 (s, 3H), 3.92 (s, 3H), 2.76 (s, 3H) ; 13 C-MR (75 MHz, CDCl 3 ): δ 156.14, 151.85, 147.66, 135.58, 135.10, 130.16, 122.80, 122.73, 98.28, 61.44, 57.23, 56.13, 25.44 ; HRMS (EI) m/z 233.1017 calcd for C 13 H 15 O 3 233.1052. 2-Methylbenzo[h]quinoline (6), [12] 1 H-MR (300 MHz, CDCl 3 ): δ 9.33 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.72-7.59 (m, 4H), 7.33 (d, J = 7.8 Hz, 1H), 2.81 (s, 3H); HRMS (EI) m/z 193.0886 calcd for C 14 H 11 193.0891 [2] V. Sridharan, C. Avendano, J. C. Menendez, Tetrahedron 2007, 63, 673-681. [3] A. G. Osborne, Tetrahedron 1983, 39, 2831-2841. [4] X.-Y. Chen, J. Shi, Y.-M. Li, F.-L. Wang, X. Wu, Q.-X. Guo, L. Liu, Org. Lett., 2009, 11, 4426 4429.

[5] T. Igarashi, T. Inada, T. Sekioka, T. akajima, I. Shimizu, Chem. Lett. 2005, 35, 106-107. [6] S. E. Ward, PCT Int. Appl. (2003), WO 2003068771 A1 20030821. [7] Z. Zhang, J. Tan, Z. Wang, Org. Lett. 2008, 10, 173-175. [8] G. Sivaprasad, R. Rajesh, P. T. Perumal, Tetrahedron Lett. 2006, 47, 1783-1785. [9] E. Y. Schmidt, E. Y. Senotrusova, I. A. Ushakov, A. I. Mikhaleva, B. A. Trofimov, Tetrahedron 2009, 65, 4855-4858. [10] F. A. Bottino, G. D. Pasquale, A. Pollicino, A. Recca, P. A. Staniland, J. Heterocycl. Chem. 1989, 26, 929-931. [11] H. Zhou, Z. Li, Z. Wang, T. Wang, L. Xu, Y. He, Q.-H. Fan, J. Pan, L. Gu, A. S. C. Chan, Angew. Chem. Int. Ed. 2008, 47, 8464-8467. [12] Z. Zhang, J. Tan, Z. Wang, Org. Lett. 2008, 10, 173-175. 2-Ethyl-3-methylquinolines (8) 2-Ethyl-3-methylquinoline (8a), [13] Viscous liquid, 1 H-MR (300MHz, CDCl 3 ) δ 8.02 (d, J = 8.4, 1H), 7.83 (s, 1H), 7.70 (d, J = 8.4, 1H), 7.61 (dd, J = 8.4, J = 7.8 Hz, 1H), 7.44 (dd, 3 J = 8.4, J = 7.8 Hz, 1H), 3.00 (q, J = 7.5, 2H), 2.49 (s, 3H), 1.37 (t, J = 7.5, 3H); MS (EI) m/z 171, calcd for C 12 H 13 171. 2-Ethyl-3,6-dimethylquinoline (8b), [13] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.91 (d, J = 8.4, 1H), 7.73 (s, 1H), 7.45 (s, 1H), 7.43 (d, J = 8.4, 1H), 2.97 (q, J = 7.2, 2H), 2.60 (s, 3H), 2.50 (s, 3H), 1.35 (t, J = 7.2, 3H); MS (EI) m/z 184 (M-1) + calcd for C 13 H 15 185. 2-Ethyl-3,7-dimethylquinoline (8c), [14] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.81 (s, 1H), 7.74 (s, 1H), 7.57 (d, J = 8.7, 1H), 7.26 (d, J = 8.7, 1H), 2.96 (q, J = 7.0, 2H), 2.51 (s, 3H), 2.43 (s, 3H), 1.36 (t, J = 7.0, 3H); MS (EI) m/z 184 (M-1) + calcd for C 13 H 15 185. 2-Ethyl-3,8-dimethylquinoline (8d) [13] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.72 (s, 1H), 7.50 (d, J = 8.1, 1H), 7.43 (d, J = 7.8, 1H), 7.30 (dd, J = 8.1, J = 7.8, 1H), 2.95 (q, J = 7.2, 2H), 2.41 (s, 3H), 1.41 (t, J = 7.5, 3H); MS (EI) m/z 184 (M-1) + calcd for C 13 H 15 185. 2-Ethyl-6-methox-3-methylquinoline (8e), [13] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.83 (d, 3 J = 9.0, 1H), 7.64 (s, 1H), 7.18 (d, 3 J = 9.0, 1H), 6.88 (s, 1H), 3.81 (s, 3H), 2.87 (q, J = 7.5, 2H), 2.37 (s, 3H), 1.41 (t, J = 7.5, 3H); MS (EI) m/z 200 (M-1) + calcd for C 13 H 15 O 201. 2-Ethyl-7-methoxy-3-methylquinoline (8f), [14] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.75 (s, 1H), 7.57 (d, J = 9.0, 1H), 7.36 (s, 1H), 7.10 (d, 3 J = 9.0, 1H), 3.93 (s, 3H), 2.96 (q, J = 7.5, 2H), 2.44 (s, 3H), 1.36 (t, J = 7.5, 3H); HRMS (EI) m/z 201.1135 calcd for C 13 H 15 O 201.1154.

2-Ethyl-6-fluoro-3-methylquinoline (8h), [15] White solid ; 1 H-MR (300 MHz, CDCl 3 ) δ 7.95-7.98 (m, 1H), 7.69 (s, 1H), 7.32-7.19 (m, 2H), 2.89 (q, J = 7.5 Hz, 2H), 2.40 (s, 3H), 1.29 (t, J = 7.5 Hz, 3H); MS (EI) m/z 188 calcd for C 12 H 12 F (M + -H) 188. 2-Ethyl-7-fluoro-3-methylquinoline (8i), Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.83 (s, 1H), 7.63-7.82 (m, 2H), 7.22 (m, 1H), 2.98 (q, J = 7.5 Hz, 2H), 2.47 (s, 3H), 1.37 (t, J = 7.5 Hz, 3H); ; 13 C-MR (75 MHz, CDCl 3 ) δ 164.149 (J CF = 30.3 Hz), 161.01, 147.62 (J CF = 12.6 Hz), 135.82, 128.96, 128.78 (J CF = 9.0 Hz), 124.48, 116.14 (J CF = 25.2 Hz), 112.45 (J CF = 20.03 Hz), 29.73, 19.20, 12.94; HRMS (EI) m/z 188.0949 calcd for C 12 H 12 F (M + -H) 188.0954. 2-Ethyl-6-chloro-3-methylquinoline (8j), [14] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.93 (d, J = 9.0, 1H), 7.70 (s, 1H), 7.64 (s, 1H), 7.52 (d, J = 9.0, 1H), 2.96 (q, J = 7.5, 2H), 2.46 (s, 3H), 1.36 (t, J = 7.5, 3H); MS (EI) m/z 205 calcd for C 12 H 12 Cl 205. 2-Ethyl-7-chloro-3-methylquinoline (8k), [14] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 8.02 (s, 1H), 7.80 (s, 1H), 7.63 (d, J = 8.7, 1H), 7.39 (d, J = 8.7, 1H), 2.96 (q, J = 7.5, 2H), 2.47 (s, 3H), 1.37 (t, J = 7.5, 3H); HRMS (EI) m/z 205.0537 calcd for C 12 H 12 Cl 205.0658. Methyl 2-ethyl-3-methylquinoline-6-carboxylate (8m), Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 8.48 (s, 1H), 8.20 (d, J = 8.9 Hz, 1H), 8.04 (d, J = 8.9 Hz, 1H), 7.92 (s, 1H), 3.98 (s, 3H),3.01 (q, J = 7.5 Hz, 2H), 2.58 (s, 3H), 1.39 (t, J = 7.5 Hz, 3H); 13 C-MR (75 MHz, CDCl 3 ) δ 166.94, 165.84, 148.50, 136.73, 130.46, 129.96, 128.75, 127.88, 127.08, 126.40, 52.28, 29.61, 19.12, 12.54; HRMS (EI) m/z 213.1150 calcd for C 14 H 15 O 2 213.1154 2-Ethyl-6-acetyl-3-methylquinoline (8o), [16] (Known compound, see [9]), Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 8.31 (s, 1H), 8.15 (s, J = 8.7, 1H), 8.04 (d, J = 8.7, 1H), 7.90 (s, 1H), 3.00 (q, J = 7.5, 2H), 2.70 (s, 3H), 2.49 (s, 3H),1.39 (t, J = 7.5, 3H); MS (EI) m/z 213 calcd for C 14 H 15 O 213. 2-Ethyl-8-fluoro-3-methylquinoline (8q), Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 7.84 (s, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.26-7.40 (m, 2H), 3.04 (q, J = 7.5 Hz, 2H), 2.50 (s, 3H), 1.38 (t, J = 7.5 Hz, 3H); 13 C-MR (75 MHz, CDCl 3 ) δ 161.58 (J CF = 161.6 Hz), 156.00, 136.74 (J CF = 11.5 Hz), 135.36 (J CF = 2.9 Hz), 130.61, 129.03, 125.25 (J CF = 8.6 Hz), 122.27 (J CF = 4.6 Hz), 112.35 (J CF = 19.4 Hz), 29.58, 19.14, 12.81; HRMS (EI) m/z 188.0951 calcd for C 12 H 12 F (M + -H) 188.0954. 2-Ethyl-3-methylbenzo[h]quinoline (10), [17] Viscous liquid, 1 H-MR (300 MHz, CDCl 3 ) δ 9.36 (s, 1H), 7.85-7.89 (m, 2H), 7.59-7.74 (m, 4H), 3.00 (q, J = 7.5, 2H), 2.50 (s, 3H), 1.50 (t, 3 J = 7.5, 3H); MS (EI) m/z 220(M-1) + calcd for C 16 H 15 221. [13] L. Li, W. D. Jones, J. Am. Chem. Soc. 2007, 129, 10707-10713. [14] C. S. Cho, B. H. Oh, S. C. Shim, D. H. Oh, J. Heterocyclic Chem. 2000, 37, 1315-1320.

[15] D.-W. Wang, X.-B. Wang, D.-S. Wang, S.-M. Lu, Y.-G. Zhou, Y.-X. Li, J. Org. Chem. 2009, 74, 2780-2787. [16] C. S. Cho, J. S. Kim, B. H. Oh, T.-J. Kim, S. C. Shim,. S. Yoon, Tetrahedron 2000, 56, 7747-7750. [17] I. Yamamoto, T. Furukawa, H. akajima, H. Gotoh, J. Chem. Soc., Perkin Trans. 1, 1976, 1597-1602. Synthesis of 2-methyl-4-anilino-1,2,3,4-tetrahydroquinoline. In a 20 ml glass flask equipped with Dimroth condenser and Teflon coated stir bar was charged with a solution of aniline (1 mmol) in 5 ml of toluene and AgO 3 (0.01 mmol, finely powdered immediately before the reaction), ethyl vinyl ether (3 mmol). After the mixture was reflux for 1h under air atmosphere, the solvent was removed by reduced pressure, and the products were isolated by a column chromatography on silica gel (hexane/benzene) to give (cis and trans (34/66))-2-methyl-4-alinino-1,2,3,4-tetrahydroquinoline (11a) [18] in 78% yield based on aniline (1/2 mol). Brown solid, 1 H MR (300 MHz, CDCl 3 ): δ 7.23 (d, J = 7.7 Hz, 1H), 7.21 (dd, J = 8.7 Hz, 7.7 Hz, 1H), 7.08 (dd, J = 8.7 Hz, J = 7.5 Hz, 1H), 6.77 (d, J = 7.5 Hz, 1H), 6.72 (dd, J = 7.5 Hz, J = 6.9 Hz, 2H), 6.66 (d, J = 7.5 Hz, 2H), 6.56 (d, J = 6.9 Hz, 1H), 4.54 (m, 1H), 3.46 (m, 1H), 3.36 (br, 2H), 2.19 (m, 1H), 1.65 (m, 1H), 1.23 (s, 3H) ; HRMS (EI) m/z 238.1466 calcd for C 16 H 18 2 238.1470. [18] H. Smith, C. K. Cavanaugh, J. L. Friz, C. S. Thompson, J. A. Saggers, E. L. Michelotti, J. Garcia, C. M. Tice, Bioorg & Med. Chem. Lett. 2003, 13, 1943-1946.

5. Reaction Profile by HPLC. Mole ratio (%) 100 80 60 40 20 1a -ethyl aniline 2a 0 5 10 15 Reaction Time (h) 20 25 Figure S1. Reaction profile for aniline (2a) and 2-methylqunoline (1a) by HPLC (ODS / MeOH : H 2 O = 7 : 3), Anthracene as internal standard: Condition: aniline = 1 mmol, ethyl vinyl ether = 3 mmol, MeC 5 ml, PdCl 2 = 5 mol%, Pd/C = 20 mg, at 80 o C under open air.

6. Formation of -Alkylaniline (Side Product). Table S1: Formation of -ethylaniline (side product) in the reaction of aniline with vinyl ether [a] 2 Et X 2 3 OEt 5mol%PdCl 2 CH 3 C, 80 o C X 1 X 1' (Side product) Entry Aniline t [h] Side product Yield [%] [b] Entry Aniline t [h] Side product Yield [%] [b] 1 X = H 2a 24 EtH 1a' 16 [d] 9 X = 3-F 2i 24 EtH 1i' F 26 2 X = 4-Me 2b 24 EtH Me 1b' 12 10 X = 4-Cl 2j 24 EtH Cl 1j' 21 3 X = 3-Me 2c 24 EtH 1c' Me 15 11 X = 3-Cl 2k 24 EtH 1k' Cl 23 4 Me X = 2-Me 2d 24 EtH 1d' 18 12 X = 4-Br 2l 24 EtH 1l' Br 21 5 6 X = 4-OMe 2e 24 EtH OMe X = 3-OMe 2f 48 EtH 1e' 1f' OMe 8 13 14 X = 4-COOMe [c] 2m 24 EtH CO OMe 1m' X = 4-COMe 2 [c] 2n 24 EtH COMe 2 1n' ~0 ~0 7 MeO X = 2-OMe 2g 4 Et H 1g' 23 15 X = 4-COMe 2o [c] 24 Et H COMe 1o' ~0 8 X = 4-F 2h 24 Et H F 1h' 0 16 X = 4-COPh [c] 2p 24 Et H COPh 1p' ~0 [a] Reaction conditions: Substituted aniline (1 mmol), ethyl vinyl ether (3 mmol), PdCl 2 (5 mol%) and Pd/C (20 mg) in MeC (5 ml) were heated at 80 o C under open air. [b] Yields were determined by HPLC. [c] Yields in the absence of Pd/C. [d] Yield was almost no change by three-fold scale up.

Table S2: Formation of -ethylaniline (side product) in the reaction of aniline with vinyl ether [a] ntry Substituted aniline Side product t [h] Yield [%] [b] 2 OMe E t OMe 1 MeO OMe 5 MeO OMe 4 96 13 2 Et 2 7 6 4 ~0 [a] Reaction condition: Substituted aniline (1 mmol), ethyl vinyl ether (3 mmol), and PdCl 2 (3 mol%) in MeC (5 ml) were heated at 80 o C under open air. [b] Yields were determined by HPLC.

Table S3: Formation of -propylaniline (side product) in the reaction of aniline with allyl ether [a] Pr X 2 2 9 OBu 10 mol% PdCl 2 MeC, 80 o C X 8 e X 8' (Sid p roduct) Entry Aniline t [h] Side product Yield [%] [b] Entry Aniline t [h] Side product Yield [%] [b] 1 X = H 2a 48 PrH 8a' 18 8 X = 3-F 2i 48 PrH 8i' F 13 2 24 X = 4-Me 2b PrH 8b' Me 16 9 X = 2-F 2q 48 PrH 8q' F 3 3 X = 3-Me 2c 48 PrH 8c' Me 15 10 X = 4-Cl 2j 48 PrH 8j' Cl 12 4 Me X = 2-Me 2d 48 PrH 8d' 8 11 X = 3-Cl 2k 48 PrH 8k' Cl 10 5 6 X = 4-OMe 2e 24 PrH OMe X = 3-OMe 2f 48 PrH 8e' 8f' OMe 13 12 13 X = 4-CO 2 Me 2m 24 PrH COOMe 8m' X = 4-COMe 2o 24 PrH COMe 8o' ~0 ~0 7 X = 4-F 2h 4 PrH F 8h' 22 14 2 10' 7 [a] Reaction conditions: Substituted aniline (1 mmol), n-butyl allyl ether (3 mmol), and PdCl 2 (10 mol%) in CH 3 C (5 ml) were heated at 80 o C under open air. [b] Yields were determined by HPLC. 48 Pr 14

Table S4: Formation of -propylaniline (side product) in the reaction of aniline with allyl ether or 1-ethoxy-1-propene [a] 2a 2 9 or OBu OEt 10 5 mol% PdCl 2 MeC, 80 o C 8a Pr 8a'(Side product) Entry Ether Additive t [h] yield of 8a [%] [b] 1 allyl n-butyl ether - 24 16 2 1-ethoxy-1-propene - 24 31 3 same as above 10 mg Pd/C 24 23 4 same as above 20 mg Pd/C 24 18 [a] Reaction condition: Aniline (1 mmol), allyl n-butyl ether or 1-ethoxy-1-propene (3 mmol), and PdCl 2 (5 mol%) in MeC (5 ml) were heated at 80 o C under open air. [b] Yields were determined by HPLC.

7. Examination Reaction Pathway. 7-1. HPLC of the reaction mixtures. 2 PdCl 2 (5 mol%) + OEt Reaction mixtures inch 3 C at 80 o C a) After 0.5 h H H H 2 Internal standard R. T. (min) Figure S2. HPLC of the reaction mixtures (0.5 h) (ODS / Eluent: MeOH : H 2 O = 8 : 2) b) After 2 h H H Internal standard H R. T. (min) Figure S3. HPLC of the reaction mixtures (2 h) (ODS / Eluent: MeOH : H 2 O = 8 : 2)

7-2. PdCl 2 -catalyzed reaction of compounds 11a (cis and trans) leading to 1a. H H PdCl 2 (5 mol%) 2 in MeC 1a 2a 11a (cis and trans) Quantitative yield Scheme S1. PdCl 2 catalyzed reaction of compounds 11a (cis and trans). 7-3. Proposed mechanism for 2-methylqunoline (1a) formation from aniline and vinyl ether. ArEt CH 3 CH Ar Pd(II) OEt Pd(H) O 2 (Pd/C) Pd(II) CH 2 CH OEt Ar 2 1a O Et Et O 2 Ar H Ar Pd(II) CH 2 C H Ar OEt I Pd(0) III Pd(II) II H Ar CH 3 CH Ar EtOH Pd(II) Ar 2 OEt Ar 2 Scheme S2. Proposed mechanism for the formation of 2-methylqunoline. 8. Proposed Reaction Sequence for the Synthesis of 2-Ethyl-3-methylqunoline (8a). CH 2 =CH-CH 2 -OR PdCl 2 H + CH 3 -CH=CH-OR 2 + CH 3 -CH=CH-OR PdCl 2 MeC Pd(0) MeC 8a (Refer to the Scheme S2 for the mechanism)