Synlett, Inhaltsverzeichnis Synlett 2013; 24(4): 475-478DOI: 10.1055/s-0032-1318159 letter © Georg Thieme Verlag Stuttgart · New York Palladium-Catalyzed Synthesis of Isoquinolinones via Sequential Cyclization and N–O Bond Cleavage of N-Methoxy-o-alkynylbenzamides Manita Jithunsa Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Hyogo 658-8558, Japan Fax: +81(78)4417554 eMail: miyata@kobepharma-u.ac.jp , Masafumi Ueda* Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Hyogo 658-8558, Japan Fax: +81(78)4417554 eMail: miyata@kobepharma-u.ac.jp , Naoki Aoi Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Hyogo 658-8558, Japan Fax: +81(78)4417554 eMail: miyata@kobepharma-u.ac.jp , Shoichi Sugita Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Hyogo 658-8558, Japan Fax: +81(78)4417554 eMail: miyata@kobepharma-u.ac.jp , Tetsuya Miyoshi Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Hyogo 658-8558, Japan Fax: +81(78)4417554 eMail: miyata@kobepharma-u.ac.jp , Okiko Miyata* Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Hyogo 658-8558, Japan Fax: +81(78)4417554 eMail: miyata@kobepharma-u.ac.jp › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Abstract A palladium-catalyzed controlled 6-endo-dig cyclization process has been developed for the chemoselective synthesis of isoquinolin-1-ones from N-alkoxy-o-alkynylbenzamides. The mechanism and scope of the reaction have also been investigated. Deuterium-labeling studies were used to confirm the intramolecular 1,5-hydrogen shift as a key step in the transformation. Key words Key wordsalkynes - regioselectivity - palladium - cyclization - amides Volltext Referenzen References and Notes 1 Onda M, Yamaguchi H. Chem. Pharm. Bull. 1979; 27: 2076 2a Trotter BW, Nanda KK, Kett NR, Regan CP, Lynch JJ, Stump GL, Kiss L, Wang J, Spencer RH, Kane SA, White RB, Zhang R, Anderson KD, Liverton NJ, McIntyre CJ, Beshore DC, Hartman GD, Dinsmore CJ. J. Med. Chem. 2006; 49: 6954 2b Cho W.-J, Park M.-J, Chung B.-H, Lee C.-O. Bioorg. Med. Chem. Lett. 1998; 8: 41 2c Ukita T, Nakamura Y, Kubo A, Yamamoto Y, Moritani Y, Saruta K, Higashijima T, Kotera J, Takagi M, Kikkawa K, Omori K. J. Med. Chem. 2001; 44: 2204 2d Cho W.-J, Kim E.-K, Park IY, Jeong EY, Kim TS, Le TN, Kim D.-D, Lee E.-S. Bioorg. Med. Chem. 2002; 10: 2953 3 Bisagni E, Landras C, Thirot S, Huel C. 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Soc. 2002; 124: 764 14 General Procedure for the Palladium-Catalyzed Synthesis of Isoquinolinone To a solution of N-alkoxy-o-alkynylbenzamide 1 (0.20 mmol) in DCE (4 mL) was added i-PrOH (0.6 mmol), p-benzoquinone (1.0 mmol), and PdCl2(PPh3)2 (0.04 mmol) under O2 atmosphere. After being refluxed for 24 h, the reaction mixture was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with EtOAc–hexane (1:3) and/or toluene–Et2O (3:1). Representative spectroscopic data of selected products are as follows. 2-Methyl-3-phenylisoquinolin-1(2H)-one (2a) Yellow solid; mp 66–67 °C (EtOAc–hexane; lit.5f 63 °C). 1H NMR (300 MHz, CDCl3): δ = 8.45 (br d, J = 7.5 Hz, 1 H), 7.64 (br t, J = 8.1 Hz, 1 H), 7.51–7.39 (m, 7 H), 6.46 (s, 1 H), 3.44 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 163.3, 143.8, 136.3, 136.1, 132.2, 128.8, 128.7, 128.5, 127.7, 126.5, 125.7, 124.7, 107.5, 34.1. IR (KBr): νmax = 1652, 1619 cm–1. ESI-HRMS: m/z calcd for C16H13NO [M + H]+: 236.1069; found: 236.1066. 3-(4-Fluorophenyl)-2-methylisoquinolin-1(2H)-one (2b) Yellow solid; mp 135–137 °C (EtOAc–hexane). 1H NMR (300 MHz, CDCl3): δ = 8.44 (d, J = 7.8 Hz, 1 H), 7.64 (t, J = 7.8 Hz, 1 H), 7.51–7.45 (m, 2 H), 7.42–7.37 (m, 2 H), 7.17 (t, J = 8.4 Hz, 2 H), 6.44 (s, 1 H), 3.41 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 164.6, 163.3, 161.3, 142.7, 136.2, 132.3, 132.2, 130.7, 130.6, 127.8, 126.7, 125.8, 124.9, 115.9, 115.6, 107.7, 34.1. IR (KBr): νmax = 1650, 1619 cm–1. ESI-HRMS: m/z calcd for C16H13ONF [M + H]+: 254.0976; found: 254.0967. 7-Chloro-2-methyl-3-phenylisoquinolin-1(2H)-one (2h) White solid; mp 148–150 °C (EtOAc–hexane). 1H NMR (300 MHz, CDCl3): δ = 8.37 (d, J = 8.4 Hz, 1 H), 7.49–7.45 (m, 4 H), 7.42–7.37 (m, 3 H), 6.36 (s, 1 H), 3.40 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 162.8, 145.4, 138.6, 137.6, 135.8, 129.7, 129.2, 128.7, 128.6, 127.1, 124.9, 123.2, 106.4, 34.1. IR (KBr): νmax = 1649, 1624 cm–1. ESI-HRMS: m/z calcd for C16H13ONCl [M + H]+: 270.0680; found: 270.0673.
