Synlett 2014; 25(16): 2301-2305
DOI: 10.1055/s-0034-1378613
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© 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
Further Information

Publication History

Received: 15 May 2014

Accepted after revision: 23 July 2014

Publication Date:
21 August 2014 (eFirst)

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.

Supporting Information

 
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  • 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.