Synlett, Table of Contents Synlett 2014; 25(16): 2301-2305DOI: 10.1055/s-0034-1378613 cluster © Georg Thieme Verlag Stuttgart · New York One-Step Synthesis of Quinolines via Palladium-Catalyzed Cross-Coupling of Cyclopropanols with Unprotected ortho-Bromoanilines Andrei Nikolaev Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada Fax: +1(416)7365936 Email: aorellan@yorku.ca , Nisha Nithiy Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada Fax: +1(416)7365936 Email: aorellan@yorku.ca , Arturo Orellana* Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada Fax: +1(416)7365936 Email: aorellan@yorku.ca › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract The cross-coupling of unprotected ortho-bromoanilines with cyclopropanols yields quinolines in a single operation via an intramolecular condensation and palladium-catalyzed oxidation sequence. The reaction tolerates a variety of cyclopropanols and substituted bromoanilines. Deuterium-labeling experiments provide direct evidence of a second equivalent of bromoaniline serving as the terminal oxidant. Key words Key wordscyclopropanol - cross-coupling - palladium - quinoline Full Text References References and Notes 1a Rosa D, Orellana A. Org. Lett. 2011; 13: 110 1b Rosa D, Orellana A. Chem. Commun. 2012; 48: 1922 1c Rosa D, Orellana A. Chem. Commun. 2013; 49: 5420 2a Nakamura E, Kuwajima I. Tetrahedron Lett. 1986; 27: 83 2b Nakamura E, Aoki S, Sekiya K, Oshino H, Kuwajima I. J. Am. Chem. Soc. 1987; 109: 8056 2c Nakamura E, Sekiya K, Kuwajima I. Tetrahedron Lett. 1987; 28: 337 2d Aoki S, Fujimura T, Nakamura E, Kuwajima I. J. Am. Chem. Soc. 1988; 110: 3296 2e Aoki S, Fujimura T, Nakamura E, Kuwajima I. Tetrahedron Lett. 1989; 30: 6541 2f Kang S.-K, Yamagushi T, Ho P.-S, Kim W.-Y, Yoon S.-K. Tetrahedron Lett. 1997; 38: 1947 2g Aoki S, Nakamura E. Synlett 1990; 741 2h Fujimura T, Aoki S, Nakamura E. J. Org. Chem. 1991; 56: 2809 2i Cheng K, Walsh PJ. Org. Lett. 2013; 15: 2298 2j Parida BB, Das PP, Niocel M, Cha JK. Org. Lett. 2013; 15: 1780 3 Nithiy N, Rosa D, Orellana A. Synthesis 2013; 45: 3199 4 Larock RC, Kuo MY. Tetrahedron Lett. 1991; 32: 569 5a Mahajan JP, Suryawanshi YR, Mhaske SB. Org. Lett. 2012; 14: 5804 5b Waibel M, Cramer N. Angew. Chem. Int. Ed. 2010; 49: 4455 5c Gowrisankar S, Lee HS, Kim JM, Kim JN. Tetrahedron Lett. 2008; 49: 1670 5d Cho CS, Kim JU. Tetrahedron Lett. 2007; 48: 3775 5e Cho CS. J. Organomet. Chem. 2005; 690: 4094 5f Mahanty JS, De M, Das PKundu N. G. Tetrahedron 1997; 53: 13397 6 Stone MT. Org. Lett. 2011; 13: 2326 7a Furukawa J, Kawabata N, Nishimura J. Tetrahedron Lett. 1966; 7: 3353 7b Furukawa J, Kawabata N, Nishimura J. Tetrahedron 1968; 24: 53 8 Kulinkovich O. Chem. Rev. 2003; 103: 2597 9a Cyclopropanols A–D and F: Rosa D, Orellana A. Chem. Commun. 2013; 49: 5420 9b Cyclopropanol E: Cheng K, Carroll PJ, Walsh PJ. Org. Lett. 2011; 13: 2346 9c Cyclopropanol G: Iwasawa N, Hayakawa S, Funahashi M, Isobe K, Narasaka K. Bull. Chem. Soc. Jpn. 1966; 66: 819 9d Cyclopropanol H: Murai S, Aya T, Sonoda N. J. Org. Chem. 1973; 38: 4354 10 Synthesis of Quinoline 1A – Representative Procedure An oven-dried vial equipped with stir bar was charged with Pd(OAc)2 (0.0055 g, 0.0245 mmol, 0.10 equiv), dppb (0.020 g, 0.0489 mmol, 0.2 equiv), and K2CO3 (0.15 g, 0.98 mmol, 4.0 equiv). Freshly distilled toluene was introduced into the vial via syringe, and the contents were allowed to stir. A second oven-dried vial equipped with a stir bar was charged with cyclopropanol A (0.05 g, 0.245 mmol, 1.0 equiv) and 2-bromoaniline (0.084 g, 0.489 mmol, 2.0 equiv). Freshly distilled toluene was introduced into the vial via syringe, and contents were allowed to stir. The solution of substrates was added to the solution containing the palladium catalyst. The reaction vial was purged with argon, capped with a rubber septum, and heated to 110 °C for 24 h. Upon completion, the reaction mixture was filtered through a pad of Celite using EtOAc and concentrated in vacuo. The crude product was purified by flash column chromatography, eluting with the indicated solvent mixture to afford the desired quinoline product. Purification by flash column chromatography using 20% EtOAc in hexanes provided the desired quinoline as a pale yellow oil (0.051 g, 0.19 mmol) in 76% yield. 1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 8.4 Hz, 1 H), 8.04 (d, J = 8.4 Hz, 1 H), 7.78 (d, J = 8.1 Hz, 1 H), 7.73 (dd, J = 8.4, 7.8 Hz, 1 H), 7.52 (dd, J = 8.4, 7.8 Hz,1 H), 7.36 (d, J = 8.1 Hz, 1 H), 7.30–7.26 (m, 3 H), 4.36 (s, 2 H), 1.33 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 161.4, 149.2, 147.8, 136.3, 136.1, 129.3, 128.9, 128.8, 127.4, 126.7, 125.8, 125.4, 121.5, 45.0, 34.3, 31.3. IR: ν = 3057, 2960, 1655, 1618, 1599, 1504, 742 cm–1. HRMS: m/z calcd for [C20H21N]+: 275.1674; found: 275.1669. Supplementary Material Supplementary Material Supporting Information
